Academic literature on the topic 'MSC'
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Journal articles on the topic "MSC"
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Peters, R. E., M. Heikenwälder, and A. Knuth. "Expansion of umbilical cord blood mesenchymal stem cells." Journal of Clinical Oncology 27, no. 15_suppl (2009): 7103. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.7103.
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7103 Background: Umbilical cord blood (UCB) is known to harbor 2 major types of stem cells, the hematopoietic stem cells (HSC) & the non-hematopoietic or mesenchymal stem cells (MSC). Under appropriate conditions, MSCs can give rise to cells of bone, fat, hepatic lineages, etc. Based on this potential, MSC hold promise for clinical applications in regenerative medicine. Methods: Stroma-free liquid culture: UCB cryopreserved mononuclear cells (MNC) were cultured in the presence of early growth factors: Flt-3 & SCF (25ng/ml), MGDF (10ng/ml) & human serum (10%). MNC derived adherent MSC were passaged at day 14 during HSC expansion & after enriching in MesenCult medium. Results: We developed a technology to generate & expand HSC & stromal/ MSC from all UCB units (5/5) at the same time using one culture system (stroma-free liquid culture). Following repeated passages, MSC count increased 357- 600-folds & CFU-Fibroblasts colonies (CFU-F) increased too (61–513 & 648–697) after 10 and 20 passages respectively. We used the CFU-F assay to demonstrate MSC activity in stromal cell formation in vitro. Phenotypically, MSC were negative for hematopoietic antigens (CD45, CD34 & CD14) & MHC class-II but >95% + for CD73, CD105, CD29, CD44 & MHC class I. To demonstrate MSC differentiation capacity in vitro, cells were incubated in various induction media to differentiate into adipocytes (fat)), osteoblasts (bone) and hepatocytes (liver) at passage 5. Following induction, positive staining with oil red O for cells of adipocyte and with alkaline phosphatase for cells of osteoblsts lineages was observed. The identity of hepatocytes was verified by the characteristic hexagonal hepatocytic shape as well as albumin, cytokeratin (CK) 18 and CK14 expression, as assessed by flow cytometry. Our data were corroborated by RT-PCR analysis. Conclusions: MSC described herein exhibit in vitro properties of multipotent stem cells. The established, stroma-free culture system facilitates expansion of MSC from all tested UCB units. Our data underline that it will be possible in the future to substitutes properly differentiated hepatocytes which might lead to efficient applications in patients suffering from various end stage liver disease. No significant financial relationships to disclose.
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Cequier, Alina, Antonio Romero, Francisco J. Vázquez, et al. "Equine Mesenchymal Stem Cells Influence the Proliferative Response of Lymphocytes: Effect of Inflammation, Differentiation and MHC-Compatibility." Animals 12, no. 8 (2022): 984. http://dx.doi.org/10.3390/ani12080984.
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Immunomodulation and immunogenicity are pivotal aspects for the therapeutic use of mesenchymal stem cells (MSCs). Since the horse is highly valuable as both a patient and translational model, further knowledge on equine MSC immune properties is required. This study analysed how inflammation, chondrogenic differentiation and compatibility for the major histocompatibility complex (MHC) influence the MSC immunomodulatory–immunogenicity balance. Equine MSCs in basal conditions, pro-inflammatory primed (MSC-primed) or chondrogenically differentiated (MSC-chondro) were co-cultured with either autologous or allogeneic MHC-matched/mismatched lymphocytes in immune-suppressive assays (immunomodulation) and in modified one-way mixed leukocyte reactions (immunogenicity). After co-culture, frequency and proliferation of T cell subsets and B cells were assessed by flow cytometry and interferon-ɣ (IFNɣ) secretion by ELISA. MSC-primed showed higher regulatory potential by decreasing proliferation of cytotoxic and helper T cells and B cells. However, MHC-mismatched MSC-primed can also activate lymphocytes (proliferative response and IFNɣ secretion), likely due to increased MHC-expression. MSC-chondro maintained their regulatory ability and did not increase their immunogenicity, but showed less capacity than MSC-primed to induce regulatory T cells and further stimulated B cells. Subsequent in vivo studies are needed to elucidate the complex interactions between MSCs and the recipient immune system, which is critical to develop safe and effective therapies.
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Soland, Melisa, Mariana Bego, Christopher D. Porada, Esmail D. Zanjani, Stephen St Jeor, and Graca Almeida-Porada. "Modulation of Mesenchymal Stem Cell Immunogenicity through Forced Expression of Human Cytomegalovirus Proteins." Blood 112, no. 11 (2008): 2416. http://dx.doi.org/10.1182/blood.v112.11.2416.2416.
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Abstract Mesenchymal stem cells (MSC) are promising candidates for cell replacement therapy since they have the ability to differentiate, under appropriate conditions, into a broad range of specialized cell types. Furthermore, MSC have low inherent immunogenicity, immunomodulatory properties, and preferentially home to/engraft damaged tissues. However, they are not invisible to the immune system, and upon allogeneic transplantation, MSC can elicit an immune response, that results in activation of the recipient’s cytotoxic T lymphocytes (CTL) and Natural Killer (NK) cells and hence rejection of the transplanted cells. Human cytomegalovirus (HCMV), a virus ubiquitously present in humans, has developed several strategies to evade CTL and NK cell recognition. HCMV avoids CTL attack by producing proteins coded for by the unique short region (US) of the genome that downregulate MHC-I surface expression. Moreover, expression of HCMV UL18 protein, which is an MHC-I homolog or decoy, renders CMV-infected cells resistant to NK lysis. Thus, we hypothesized that simultaneous expression of HCMV US protein US2, US3, US6, or US11 with UL18 would render MSC less susceptible to CTL and NK cell recognition and killing. To this end, we started by transducing MSC with the retroviral vectors encoding: US2; US3; US6; or US11, and tested the effect of each of these proteins on expression of MHC-I and CD59, a complement membrane attack complex inhibitor whose expression has been shown to prevent destruction of transplanted cells. MSC expressing US3, US2, US11 and US6 showed substantial MHC-I downregulation of 69%, 74%, 78 % and 95% respectively, when compared to untransduced MSC. Moreover, MSC expressing either US6 or US2 proteins displayed a significant up-regulation of CD59, with US6 causing a 2.5 and US2 a 3.9 fold increase, when compared to untransduced MSC (Mean Fluorescence Intensity: 869.8; 1331.19; 344.99, respectively). Each of the US transduced MSC were then tested for their capability to activate MHC-I mismatched CTL proliferation in both an allogeneic and a xenogeneic setting, using MSC transduced with an empty retrovirus as a control. MSC expressing US2 or US6 reduced CTL proliferation by the same degree, whether CTL were mismatched human- or sheep-derived. Using MSC-US2 we obtained a reduction in CTL proliferation by 18% and 23% in human-or sheep-CTL, respectively, while using MSC-US6 resulted in a reduction in human and sheep CTL proliferation of 60% and 53%. Expression of US11 on MSC was more efficient at abrogating the sheep CTL proliferation than that of mismatched human CTL (reduction in proliferation by 53% vs 31%, respectively). Finally, expression of US3 on MSC only reduced proliferation of human CTL by 21.5%, but had no effect on sheep CTL. In conclusion, engineering MSC to over-express US6 seems to be the most effective way to enable MSC to evade the host immune system, resulting in efficient downregulation of MHC-I surface expression, significant reduction in CTL proliferation, and a reduced formation of the membrane attack complex at the end of the complement cascade, which will reduce destruction of MSC by this system. In vivo studies using a large animal sheep model are underway to demonstrate whether the results obtained in vitro using US6 HCMV protein expression will translate into improved engraftment in vivo.
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Laranjeira, Paula, Joana Gomes, Susana Pedreiro, et al. "Human Bone Marrow-Derived Mesenchymal Stromal Cells Differentially Inhibit Cytokine Production by Peripheral Blood Monocytes Subpopulations and Myeloid Dendritic Cells." Stem Cells International 2015 (2015): 1–15. http://dx.doi.org/10.1155/2015/819084.
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The immunosuppressive properties of mesenchymal stromal/stem cells (MSC) rendered them an attractive therapeutic approach for immune disorders and an increasing body of evidence demonstrated their clinical value. However, the influence of MSC on the function of specific immune cell populations, namely, monocyte subpopulations, is not well elucidated. Here, we investigated the influence of human bone marrow MSC on the cytokine and chemokine expression by peripheral blood classical, intermediate and nonclassical monocytes, and myeloid dendritic cells (mDC), stimulated with lipopolysaccharide plus interferon (IFN)γ. We found that MSC effectively inhibit tumor necrosis factor- (TNF-)αand macrophage inflammatory protein- (MIP-) 1βprotein expression in monocytes and mDC, without suppressing CCR7 and CD83 protein expression. Interestingly, mDC exhibited the highest degree of inhibition, for both TNF-αand MIP-1β, whereas the reduction of TNF-αexpression was less marked for nonclassical monocytes. Similarly, MSC decreased mRNA levels of interleukin- (IL-) 1βand IL-6 in classical monocytes, CCL3, CCL5, CXCL9, and CXCL10 in classical and nonclassical monocytes, and IL-1βand CXCL10 in mDC. MSC do not impair the expression of maturation markers in monocytes and mDC under our experimental conditions; nevertheless, they hamper the proinflammatory function of monocytes and mDC, which may impede the development of inflammatory immune responses.
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Giallongo, Cesarina, Daniele Tibullo, Nunziatina Laura Parrinello, et al. "Mesenchymal Stem Cells (MSC) from Patients with Multiple Myeloma Promote Myeloid Cells to Become Granulocytic-Myeloid-Derived Suppressor Cells (G-MDSC) with Immunosuppressive, Bone Resorption and Pro-Angiogenic Activity." Blood 128, no. 22 (2016): 4458. http://dx.doi.org/10.1182/blood.v128.22.4458.4458.
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Abstract Purpose A well-recognized feature of MM is the intimate relationship between plasma cells and bone marrow microenvironment, which is mainly composed of MSC, endothelial cells, immune cells and extracellular matrix. G-MDSC accumulate in the tumor microenvironment during tumor development promoting tumor growth and immunosuppression. Aim Analyzing MSC from MGUS, Smoldering myeloma (SMM) and MM patients in promoting G-MDSC generation. Methods Human peripheral blood mononucleated cells (PBMC) isolated from healthy subjects (HS) were cultured alone and with HS- (n=10), MGUS- (n=10), SMM- (n=4) or MM-MSC (n=14)(1:100). After 6 days, G-MDSC were isolated using anti-CD66b magnetic microbeads and the phenotype(CD11b+CD33+CD14-HLADR-) was confirmed by cytofluorimetric analysis. Results Only G-MDSC educated by SMM- and MM-MSC co-cultures (MSCed-G-MDSC) were able to suppress T cell proliferation when cultured with normal lymphocytes (p<0.001) compared to G-MDSC control (isolated from PBMC cultured in medium alone). SMM- and MM-MSCed-G-MDSC significantly up-regulated Arg1, NOS2, TNFα and CEBPA, a transcription factor promoting suppressive phenotype. Since also the angiogenic factor BV8 was significantly up-regulated, we next investigated the pro-angiogenic effect in vitro co-culturing MSCed-G-MDSC with Human Brain Microvascular Endothelial Cells (HBMEC) (1:2). After 5 h, we observed that MM-MSCed-G-MDSC were able to increase both tube length and number of branch points compared to G-MDSC control (p<0.05). Moreover, MM-MSCed-G-MDSC were able to digest bone matrix in vitro (p<0.01). Adding Bortezomib (5 nM), Lenalidomide (10 μM) or Pomalidomide (1 nM) during co-culture with MM-MSC, isolated G-MDSC showed a significant reduction of pro-angiogenic and bone resorption activity (p<0.05) but did not lose immunosuppressive ability. Conclusion MSC play a key role promoting tumor microenvironment transformation in SMM and MM patients.Indeed, only SMM- and MM-MSC and not MGUS-MSC are able to activate myeloid cells in G-MDSC with immunosuppressive, pro-angiogenic, and bone resorptionactivity. Disclosures No relevant conflicts of interest to declare.
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Maijenburg, Marijke, Marion Kleijer, Erik Mul, Floris van Alphen, Ellen van der Schoot, and Carlijn Voermans. "Primary Bone Marrow-Derived MSC Subsets with Distinct Wnt Expression Profiles Are Dynamically Distributed During Human Life." Blood 116, no. 21 (2010): 2590. http://dx.doi.org/10.1182/blood.v116.21.2590.2590.
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Abstract Abstract 2590 Mesenchymal stromal cells (MSC) in bone marrow (BM) consist of a heterogeneous population of cells. MSC orchestrate the BM microenvironment, and therefore have a pivotal role in hematopoietic support. Since MSC produce a large quantity and variety of Wnt proteins, it is likely that Wnts are involved in their hematopoietic support function Recent studies show enrichment for BM-derived MSC by sorting for CD271+ or CD146+ cells. However, it is unclear whether these markers are co-expressed with classical markers MSC markers CD73, CD105 and CD90. In addition mainly adult samples were studied, while it is known that MSC frequency declines with age. Most in-vitro studies with MSC as well as all therapeutic applications have been performed with a heterogeneous population of cultured cells. In this study we first characterized the different MSC subpopulations in BM from 81 donors (adult n=55 mean age 62 (19-82), pediatric n=22 mean age 4 (0-16) and fetal n=6, second trimester) by 6-color FACS analysis. Next we analyzed the subsets with respect to their distribution in different age groups, colony forming ability, and Wnt (target)-gene expression compared to cultured MSC. Three putative MSC subsets were identified in CD45−/dimCD34− cells from adult BM, based on expression of CD271 and/or CD146, CD105 and CD90. These populations were CD271brightCD146−CD105+CD90+, CD271brightCD146+CD105+CD90+ and CD271−CD146+CD105+CD90+, hereafter referred to CD271 single positive (sp) (0.011±0.001% from the mononuclear cell fraction (MNC)), double positive (0.003±0.001% from MNC) and CD146 sp (0.007±0.001%). The largest population of putative MSC in adult BM was CD271 sp (n=55, 55.9±24.3%). In contrast to adult BM, in pediatric BM the dominant population was double positive (n=22, 78.2±20.9%, 0.0115±0.003% MNC count), while the CD271 sp (0.0005±0.001% from MNC) and CD146 sp (0.0005±0.0001% from MNC) populations contained less than 25% of the CD271 and/or CD146+ cells. Remarkably, in fetal BM CD146 sp cells accounted for 35.5±8.8% (0.107±0.004% from MNC) of all presumptive MSC. Double positive cells represented 60.8±8.2% (0.1739±0.025% from MNC). CD271 sp cells, dominant in adults, were nearly absent (0.0115% ±0.004% from MNC)in fetal BM. The proportion of CD271 sp cells in BM was positively correlated with donor age (n=83, R2=0.41, p<0.000). Distribution of double positive cells was inversely correlated (n=83, R2=0.39, p<0.000). These data show that MSC subset composition changes with donor age, with CD271 sp cells dominant in adults and double positive cells dominant in pediatric and fetal BM. For verification of MSC content defined by CFU-F formation, the subpopulations were sorted. In adults CFU-F were observed in CD271 sp and double positive fraction (n=7) but not in CD146 sp cells, except for one donor. These data are in line with other reports that only describe CFU-F in the CD271bright population. In pediatric BM, only the double positive fraction contained CFU-F, whereas in fetal BM both double positive and CD146 sp cells gave rise to CFU-F. Thus not only distribution, but also CFU-F content of MSC subsets differs with donor age. To investigate whether the different subsets defined by our 6 marker FACS analysis might play different roles in hematopoietic support, we investigated by PCR-array the expression of Wnt- and Wnt-related genes. Indeed, clear differences in Wnt-(target)gene expression in the three primary adult MSC subsets were found, which were also quite different from the culture expanded MSC. Wnt5a and the Wnt target genes CCND1 and PP2CA were highly expressed in cultured MSC only. LRP6, FZD7 and Wnt11 were not detected in the CD271sp subset, but strongly expressed by the double positive cells. Thus, primary MSC subsets in adult BM may have different supportive functions through Wnt signaling. In conclusion, our data show that at least three MSC subsets are identified by expression of CD271 and/or CD146. In adults, these subsets have distinct Wnt signaling profiles. Moreover, we show for the first time that distribution of defined stromal cell subsets is significantly correlated with donor age. We hypothesize that MSC may comprise a dynamic system during human life, in which different subpopulations may have different functions during bone marrow development, homeostasis and regeneration. Disclosures: No relevant conflicts of interest to declare.
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Robinson, Simon N., Paul J. Simmons, Nathalie Brouard, et al. "Efficacy of ‘Off-the-Shelf’, Commercially-Available, Third-Party Mesenchymal Stem Cells (MSC) in Ex Vivo Cord Blood (CB) Co-Culture Expansion." Blood 110, no. 11 (2007): 4106. http://dx.doi.org/10.1182/blood.v110.11.4106.4106.
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Abstract INTRODUCTION: Our previous studies have shown that clinically-relevant levels of hematopoietic stem and progenitor cell (HSPC) expansion are possible by ex vivo co-culture of cord blood (CB) mononuclear cells (MNC) with third-party bone marrow (BM)-derived mesenchymal stem cells (MSC) and growth factors.1 A recently activated M. D. Anderson protocol requires that BM from a haplo-identical family member be used for the de novo generation of sufficient MSC for subsequent co-culture, a process requiring ∼3 weeks. Time constraints, uncertainties associated with the identification of a suitable BM donor and potential variation in MSC performance make logistical execution of this strategy difficult. We therefore investigated the potential efficacy of ‘off-the-shelf’ commercially-available sources of MSC. Since MSC do not express HLA-II (DR) they are non-immunogenic, suggesting that this might be a valuable alternative strategy. We compared ex vivo CB HSPC expansion obtained following CB MNC co-culture with 2 commercially-available research-grade MSC isolated by density separation and plastic adherence (MSC#1, Cambrex, Walkersville, MD and MSC#2, Allcells, Emeryville, CA). A third MSC, isolated by Stro-12 selection (MSC#3, supplied by PJS) was also evaluated. METHODS: Two MDACC frozen CB units (CB#1&2) were thawed, washed and co-cultured with adherent monolayers from each MSC. Total nucleated cell (TNC) and HSPC (CD34+ cells and colony-forming units, CFU) numbers were measured at input (Day 0) and output (Day 14). RESULTS: TNC and HSPC numbers revealed that the 2 commercially-available research-grade MSC (MSC#1&2) supported ex vivo CB HSPC expansion. MSC TNC CB34+ CFU n/a - not available CB#1 #1 x 6 x23 n/a #2 x 3 x 8 x15 #3 x 6 x16 x23 CB#2 #1 x 7 x20 x31 #2 x 5 x10 x20 #3 x10 x16 x34 1 Robinson et al. x13 x14 x25 MSC#2 performed less well than MSC#1 for both CB units suggesting that variation may exist between individual MSC. These data suggest that the screening of clinical-grade MSC that perform optimally during ex vivo expansion co-culture might be warranted to best utilize this ‘off-the-shelf’ strategy. Data were similar to previous reports where TNC, CD34+ and CFU numbers were shown to increase approximately 13, 14 and 25-fold, respectively.1 Data were also similar for MSC#3, suggesting that the method used to isolate MSC does not appear to be an important variable for effective CB MNC/MSC co-culture. CONCLUSION: Although research-grade MSC were compared from different commercial sources, these data suggest that, in principle, commercially-available clinical-grade MSC might prove a valuable ‘off-the-shelf’ option, potentially reducing the time to therapy and addressing concerns associated with identifying a BM donor and variation in MSC performance. Future studies will evaluate FDA-compliant MSC that could be used clinically.
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Salgar, Shashikumar K., E. Manning, S. Li, et al. "Interleukin-10 delivery via mesenchymal stem cells (MSC) to prevent ischemia/reperfusion injury in lung transplantation (141.46)." Journal of Immunology 182, no. 1_Supplement (2009): 141.46. http://dx.doi.org/10.4049/jimmunol.182.supp.141.46.
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Abstract Ischemia-reperfusion injury (IR) is an important cause for lung graft loss (~30%). In this study, MSC & viral interleukin-10 (vIL-10) engineered MSC were tested for their ability to prevent lung IR injury. Bone marrow derived MSC from Lewis rat were transduced with rvIL-10-retrovirus & selected on neomycin. Following 120 min of left lung ischemia induction, Group A, rats received vIL-10-MSC (~15 x 106; i.v.); Group B, empty vector engineered MSC; Group C, MSC; Group D, saline; and Group E, no ischemia or MSC. Mean blood oxygenation (PaO2/FiO2 ratio, mmHg) was reduced (P&lt;0.05) at 24h post-IR injury in Group B (138±86; n=9) & Group D (87±39; n=10), compared to MSC-vIL10 (353±105; Group A; n=10) group. By days 3 & 7 with MSC-vIL10 oxygenation was normal (475±55 & 435±33; n&gt;9); by 4h it was 319±94 (n=7). MSC (passage ≤6) increased PaO2/FiO2 (454 ± 59; n=5) by 24h post-IR. Bronchoalveolar lavage at 24h post-MSC-vIL10 therapy reduced (P&lt;0.05) granulocytes, CD4 & CD8 T cells. Lung injury score (histopathology) was higher (P&lt;0.05) with no treatment (3.5 ± 1.3; n=5) compared to MSC-vIL10 (1.21± 0.6; n=7) & MSC (1.6±0.9; n=6) treated groups. Lung microvascular permeability & wet:dry ratio were lower (P&lt;0.05) in MSC-vIL10 group. IL-1α, MCP-1α, MIP-1α, & IL1-β were increased in IR injured lung. ISOL (in situ staining for DNA fragmentation) & CASPACE-3 demonstrated reduced (p&lt;0.05) number of apoptotic cells in MSC-vIL10 treated lungs. Ex vivo, expanded MSC were CD34-, CD31+ & CD45+ (5-10%), CD29+, CD90+ & CD44+ (65-95%), CD80 (0%), CD 86 (8%), MHC Class I+ (23-57%), & MHC Class II-. MSC & IL-10 delivery via MSC to prevent lung transplant IR injury seems promising.
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Giallongo, Cesarina, Nunziatina L. Parrinello, Daniele Tibullo, et al. "Mesenchymal STEM CELLS Favor Tumor Growth By Generating Granulocyte-like Myeloid Derived Suppressor CELLS in CML Patients." Blood 126, no. 23 (2015): 4018. http://dx.doi.org/10.1182/blood.v126.23.4018.4018.
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Abstract INTRODUCTION. The complex interplay between cancer cells and immune system allows neoplastic cells to evade immune surveillance and expand. Recently, our and another group have demonstrated that a subpopulation of myeloid cells, defined as "granulocytic myeloid-derived suppressor cells" (G-MDSC), plays an important role for immune escape in chronic myeloid leukemia (CML) patients by reducing T cell activation. The aim of this study was to evaluate the influence of Mesenchymal stem cells (MSC) on generation of MDSCs by comparing CML MSCs (n=10) with healthy donors (HD) MSC (n=8). METHODS. G-MDSC (CD11b+CD33+CD14-HLADR- cells) were analyzed in peripheral blood (PB) of 20 healthy donors (HD) and 30 CML patients at diagnosis by cytofluorimetric analysis. Immuno-suppressive activity was tested through incubation of G-MDSC with autologous CFSE-labeled T cells and stimulation with phytohaemagglutinin (PHA). Controls included a positive T cell proliferation control (T cells plus PHA) and a negative one (T cells only). After three days, T cell proliferation was analyzed by flow cytometry. For G-MDSC generation, human peripheral blood mononucleated cells (PBMC) from HD were cultured alone and with MSC of CML (n=10) or HD (n=8) (1:100 ratio). After one week, G-MDSC were isolated using anti-CD66b magnetic microbeads and the phenotype was confirmed by cytofluorimetric analysis. Expression of ARG1, NOS2, PTGS2, TNFα, TGFβ, IL6, IL10, IL1β was also evaluated using real time PCR. RESULTS. Percentage of cells with a G-MDSC phenotype was greater in PB obtained from CML patients than HD (82.5±9.6% vs 56,2±5.4%, p<0.0001). G-MDSC were able to inhibit T cell proliferation compared to positive control (25±5% vs 48±7.6%, p=0.0057). To investigate if CML MSC may be involved in G-MDSC generation, we incubated HD PBMC with CML or HD MSC for one week. After magnetic isolation, we found that only CML MSC-educated G-MDSC acquired immune-suppressive ability, inhibiting T cell proliferation compared to G-MDSCs control (isolated from PBMC cultured in medium alone) (32±12% vs 63±5.9%, p=0.003). On the contrary, HD MSC-educated G-MDSC did not show any suppressive effect. We also found that CML MSC-educated G-MDSC expressed higher level of the following immune modulatory factors: TNFα (20.8±19.3, p=0.006), IL1β (47.3±25.2, p=0.001), PTGS2 (20.7±10.9, p=0.002) and IL6 (33.8±13.9, p=0.004) compared to HD MSC-educated G-MDSCs (arbitrarily 2-ΔΔCt value: 1). MSC WE also observed ane an up-regulation of PTGS2 (19±4.4, p=0.04), TGFβ (6±3, p=0.01) and IL6 (5±2.8, p=0.04) in CML MSCs at time 0 with a great variability among the patients (calculated value of 2-ΔΔCt in HD MSC was 1). After 48 h of co-culture with PBMC, CML MSC showed statistically significant up-regulation of ARG1 (23.5±11.9, p=0.02), TGFβ (4.8±3, p=0.04), IL10 (5.6±2.8, p=0.03) and IL6 (54.3±23, p=0.02) expression, suggesting that multiple mechanisms are involved in MDSC induction by CML MSC. CONCLUSION. Our work demonstrates that CML MSCs are able to activate MDSCs favoring cancer immune evasion in CML patients. Disclosures Palumbo: Novartis: Honoraria, Other: Advisory Board.
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Salgar, Shashikumar, S. Li, M. Hernandez, et al. "Recipient Conditioning with Mesenchymal Stem Cells and Interleukin-10 Prolonged Cardiac Allograft Survival (102.1)." Journal of Immunology 178, no. 1_Supplement (2007): S204. http://dx.doi.org/10.4049/jimmunol.178.supp.102.1.
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Abstract Mesenchymal Stem Cells (MSC) and viral interleukin-10 (vIL-10) have immunosuppressive properties. In this study, we tested their ability to prevent cardiac allograft rejection. Bone marrow derived MSC from Lewis rat were expanded ex vivo and transduced with rvIL-10-retrovirus. Autologous MSC or vIL-10 transduced MSC were injected (~25 x 106; i.v.) into irradiated (4 Gy) rat (RT1.Al). Six weeks later heterotopic heart (RT1.An) transplantation (Tx) was performed. MSC therapy prolonged (P&lt;0.05) cardiac allograft survival (14±1 days; n= 4) compared to untreated controls (7±1 days; n=4). Also, vIL-10-MSC treatment prolonged (P&lt;0.01) graft survival (38±1 days; n=6) compared to empty vector treated group (15±1 days; n=4). In vIL-10-MSC preconditioned animals that received donor bone marrow after heart Tx, graft survival was 22±2 days (n=8). Intragraft expression of co-stimulatory molecule (CD80) and cytokines (IL-2, IFN-γ) as determined by RT-PCR was lower (P&lt;0.03) in vIL-10-MSC treated grafts compared to untreated control grafts. Ex vivo expanded MSC were CD34−, CD45+(5 %), CD29+(90%), CD80 (0%), CD 86 (8%), CD90+(93%), MHC Class I+(23–57%), and MHC Class II- as determined by FACS. Both vIL-10 and empty vector engineered MSC expressed CD29 (&gt;95%) but not other molecules. The vIL-10-MSC produced ~ 6 ng/ml of vIL-10 ex vivo. vIL-10-MSC addition in MLR cultures inhibited lymphoproliferative response (P&lt;0.05). TGF-β expression in stimulated (TNF-α or IL1-β) and unstimulated MSC was 46 – 65% of β-actin. IL-2, IL-4, IL-10, IFN-γ, and TNF-α expression was negligible in MSC (0–7% of β-actin). VEGF and HGF mRNA expression in MSC was 58% and 5% of β-actin, respectively. TgGFP+ MSC were demonstrable in various tissues for &gt;28 days. Both MSC and vIL-10 conditioning to promote allograft survival seems promising.
Dissertations / Theses on the topic "MSC"
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Comaga, Kerim. "MSc Architecture." Thesis, KTH, Arkitektur, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-298483.
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This project has revolved around how to expand Stockholm in socially sustainable way. As is the case with many other cities in the world, inspired by modernist ideals, expansion during the 1900: s have shaped Stockholm into an archipelago of islands with mostly homogenous housing types that exist within an urban structure of centre and periphery. The Stockholm City Council is trying counter this situation by expanding the city centre into eight new regional cores by densifying a few chosen areas. This is done by conforming to old traditions of placing existing housing types and public spaces in a similar way as before. How do you go one step further in decentralizing Stockholm and breaking away from these traditions? The idea for this project is then to create an alternative typology that will be spread out homogeneously throughout the regional cores and that will grow organically as new needs emerge over time. The typology itself is simply a building scaffolding, a 6x6x7 steel grid, that will act as a tool for urban planning and host creation and expansion of new housing and public situations that together aim to constitute new parts of an alternative type of growing city centre.
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Weber, Sérgio. "ASPE/MSC." Florianópolis, SC, 2005. http://repositorio.ufsc.br/handle/123456789/102368.
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Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Ciência da Computação<br>Made available in DSpace on 2013-07-16T00:46:12Z (GMT). No. of bitstreams: 1
224905.pdf: 5536445 bytes, checksum: 9c37dced0f425adf455a3f6d0fa8b466 (MD5)<br>Segundo dados do ministério da ciência e tecnologia (MCT), o mercado brasileiro na área de software é composto predominantemente por micro e pequenas empresas (MPEs), cujos processos são executados geralmente de modo informal, improvisado e com pouca visibilidade. Esse cenário gera uma série de dificuldades a essas organizações, tornando-as enfraquecidas para competir no mercado e crescerem. Uma alternativa para a mudança desse quadro é o investimento em estabelecimento de processos sistemáticos de software, já que a qualidade dos produtos desenvolvidos são altamente influenciados pelos seus processos de produção.
Nesse contexto, o presente trabalho propõe e avalia a abordagem ASPE/MSC (Approach for Software Process Establishment in Micro and Small Companies), cujo objetivo é estabelecer processos de software em MPEs, considerando suas características e limitações. Seu desenvolvimento está baseado em estudos sobre estabelecimento de processos de software, na adaptação de técnicas e abordagens existentes nessa área de pesquisa e na experiência em modelagem de processos de software, obtida pelo LQPS - Laboratório de Qualidade e Produtividade de Software da UNIVALI e pelo Grupo de Qualidade de Software do centro GeNESS. A avaliação da abordagem é realizada por meio de dois estudos de caso, executados em duas pequenas empresas de software em Florianópolis/SC.
Os principais resultados do trabalho são a abordagem ASPE/MSC e as experiências obtidas com a execução dos estudos de caso, que incluem dados qualitativos e quantitativos. A abordagem ASPE/MSC está documentada na forma de um guia, que descreve detalhadamente as atividades que a compõem, os papéis envolvidos na execução das respectivas atividades, templates de documentos para auxiliar na sua aplicação e diretrizes para sua execução num contexto real.
A perspectiva do trabalho é auxiliar micro e pequenas empresas de software a se fortalecerem no mercado, através da melhoria contínua dos seus processos. Com isso, espera-se que, MPEs possam alcançar gradativamente patamares mais elevados de qualidade, produtividade e competitividade.
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Jentsch, Lothar, and David Natroshvili. "Three-dimensional mathematical Problems of thermoelasticity of anisotropic Bodies." Universitätsbibliothek Chemnitz, 1998. http://nbn-resolving.de/urn:nbn:de:bsz:ch1-199800967.
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CHAPTER I. Basic Equations. Fundamental Matrices. Thermo-Radiation Conditions
1. Basic differential equations of thermoelasticity theory
2. Fundamental matrices
3. Thermo-radiating conditions. Somigliana type integral representations
CHAPTER II. Formulation of Boundary Value and Interface Problems
4. Functional spaces
5. Formulation of basic and mixed BVPs
6. Formulation of crack type problems
7. Formulation of basic and mixed interface problems
CHAPTER III. Uniqueness Theorems
8. Uniqueness theorems in pseudo-oscillation problems
9. Uniqueness theorems in steady state oscillation problems
CHAPTER IV. Potentials and Boundary Integral Operators
10. Thermoelastic steady state oscillation potentials
11. Pseudo-oscillation potentials
CHAPTER V. Regular Boundary Value and Interface Problems
12. Basic BVPs of pseudo-oscillations
13. Basic exterior BVPs of steady state oscillations
14. Basic interface problems of pseudo-oscillations
15. Basic interface problems of steady state oscillations
CHAPTER VI. Mixed and Crack Type Problems
16. Basic mixed BVPs
17. Crack type problems
18. Mixed interface problems of steady state oscillations
19. Mixed interface problems of pseudo-oscillations
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Jentsch, L., D. Natroshvili, and I. Sigua. "Mixed Interface Problems of Thermoelastic Pseudo-Oscillations." Universitätsbibliothek Chemnitz, 1998. http://nbn-resolving.de/urn:nbn:de:bsz:ch1-199801150.
Full textAbstract:
Three-dimensional basic and mixed interface problems of the mathematical
theory of thermoelastic pseudo-oscillations are considered for piecewise homogeneous
anisotropic bodies. Applying the method of boundary potentials and the theory of
pseudodifferential equations existence and uniqueness theorems of solutions are proved
in the space of regular functions C^(k+ alpha) and in the Bessel-potential (H^(s)_(p))
and Besov (B^(s)_(p,q)) spaces. In addition to the classical regularity results
for solutions to the basic interface problems, it is shown that in the mixed interface
problems the displacement vector and the temperature are Hölder continuous with
exponent 0<alpha<1/2.
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Jentsch, L., and D. Natroshvili. "Interaction between Thermoelastic and Scalar Oscillation Fields (general anisotropic case)." Universitätsbibliothek Chemnitz, 1998. http://nbn-resolving.de/urn:nbn:de:bsz:ch1-199801162.
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Three-dimensional mathematical problems of the interaction between thermoelastic
and scalar oscillation fields are considered in a general anisotropic case. An elastic
structure is assumed to be a bounded homogeneous anisortopic body occupying domain
$\Omega^+\sub\R^3$ , where the thermoelastic field is defined, while in the
physically anisotropic unbounded exterior domain $\Omega^-=\R^3\\ \overline{\Omega^+}$
there is defined the scalar field. These two fields
satisfy the differential equations of steady state oscillations in the corresponding
domains along with the transmission conditions of special type on the interface
$\delta\Omega^{+-}$. Uniqueness and existence theorems, for the non-resonance case, are proved
by the reduction of the original interface problems to equivalent systems of boundary
pseudodifferential equations ($\Psi DEs$) . The invertibility of the corresponding
matrix pseudodifferential operators ($\Psi DO$) in appropriate functional spaces is
shown on the basis of generalized Sommerfeld-Kupradze type thermoradiation conditions
for anisotropic bodies. In the resonance case, the co-kernels of the $\Psi DOs$ are
analysed and the efficent conditions of solvability of the transmission problems
are established.
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Jentsch, L., and D. Natroshvili. "Thermoelastic Oscillations of Anisotropic Bodies." Universitätsbibliothek Chemnitz, 1998. http://nbn-resolving.de/urn:nbn:de:bsz:ch1-199800871.
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The generalized radiation conditions at infinity of Sommerfeld-Kupradze type are established in the theory of thermoelasticity of anisotropic bodies. Applying the potential method and the theory of pseudodifferential equations on manifolds the uniqueness and existence theorems of solutions to the basic three-dimensional exterior boundary value problems are proved and representation formulas of solutions by potential type integrals are obtained.
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Jung, M., and U. Rüde. "Implicit extrapolation methods for multilevel finite element computations." Universitätsbibliothek Chemnitz, 1998. http://nbn-resolving.de/urn:nbn:de:bsz:ch1-199800516.
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Extrapolation methods for the solution of partial differential equations are commonly based on the existence of error expansions for the approximate solution. Implicit extrapolation, in the contrast, is based on applying extrapolation indirectly, by using it on quantities like the residual. In the context of multigrid methods, a special technique of this type is known as \034 -extrapolation. For finite element systems this algorithm can be shown to be equivalent to higher order finite elements. The analysis is local and does not use global expansions, so that the implicit extrapolation technique may be used on unstructured meshes and in cases where the solution fails to be globally smooth. Furthermore, the natural multilevel structure can be used to construct efficient multigrid and multilevel preconditioning techniques. The effectivity of the method is demonstrated for heat conduction problems and problems from elasticity theory.
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Natroshvili, David, and Shota Zazashvili. "The Interface Crack Problem for Anisotropic Bodies." Universitätsbibliothek Chemnitz, 1998. http://nbn-resolving.de/urn:nbn:de:bsz:ch1-199800979.
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The two-dimensional interface crack problem is investigated for anisotropic bodies in the Comninou formulation. It is established that, as in the isotropic case, properly incorporating contact zones at the crack tips avoids contradictions connected with the oscillating asymptotic behaviour of physical and mechanical characteristics leading to the overlapping of material. Applying the special integral representation formulae for the displacement field the problem in question is reduced to the scalar singular integral equation with the index equal to -1. The analysis of this equation is given. The comparison with the results of previous authors shows that the integral equations corresponding to the interface crack problems in the anisotropic and isotropic cases are actually the same from the point of view of the theoretical and numerical analysis.
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Coquery, Nicolas [Verfasser]. "Intrahippocampal transplantation of MSC and MSC-expressing BDNF in Rat Models of Depression-like Behaviour / Nicolas Coquery." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2009. http://d-nb.info/1023665360/34.
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Leonard, Martha Maria. "A description of final year nursing students' ability to recognize abnormal vital signs recordings and clinical decision-making process." Master's thesis, University of Cape Town, 2014. http://hdl.handle.net/11427/6663.
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Includes abstract.<br>Includes bibliographical references.<br>The aim of this study was to determine whether final year nursing students can recognize and respond to abnormal vital sign recordings, and to analyse their clinical decision-making processes.
Books on the topic "MSC"
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Great Britain. Central Research Administration Unit., ed. MSC research. Manpower Services Commission, Central Research Administration Unit, 1985.
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Cifuentes, Arturo O. Using MSC/NASTRAN. Springer New York, 1989. http://dx.doi.org/10.1007/978-1-4613-8917-0.
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Corporation, MacNeal-Schwendler, ed. MSC/NASTRAN bibliography. 2nd ed. MacNeal-Schwendler Corp., 1993.
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Corporation, MacNeal Schwender, ed. MSC/NASTRAN bibliography. 2nd ed. MacNeal-Schwendler Corp, 1993.
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TVEI-related In-Service Training for Teachers., ed. MSC summative report. TVEI Unit, 1987.
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Science, Brunel University Department of Computer. Exam papers: MSc, 1990. Brunel University, 1990.
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Great Britain. Manpower Services Commission. Central Research Administration Unit. MSC research 1985/86. the Commission, 1986.
Find full text
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Brunel University. Department of mechanical engineering. Exam papers: MSc 1993. Brunel University, 1993.
Find full textBook chapters on the topic "MSC"
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Vogel, Burkhard. "Miscellaneous (MSC)." In How to Gain Gain. Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/978-3-642-33033-9_34.
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Murthy, D. N. P., and Nat Jack. "EW/MSC Processes." In Springer Series in Reliability Engineering. Springer London, 2014. http://dx.doi.org/10.1007/978-1-4471-6440-1_6.
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Lohrey, Markus, and Anca Muscholl. "Bounded MSC Communication." In Lecture Notes in Computer Science. Springer Berlin Heidelberg, 2002. http://dx.doi.org/10.1007/3-540-45931-6_21.
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Biala, Jacek. "BSS-MSC-Schnittstelle." In Mobilfunk und Intelligente Netze. Vieweg+Teubner Verlag, 1996. http://dx.doi.org/10.1007/978-3-322-87270-8_11.
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Biala, Jacek. "BSS-MSC-Schnittstelle." In Mobilfunk und Intelligente Netze. Vieweg+Teubner Verlag, 1994. http://dx.doi.org/10.1007/978-3-322-83660-1_11.
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Cifuentes, Arturo O. "Introduction." In Using MSC/NASTRAN. Springer New York, 1989. http://dx.doi.org/10.1007/978-1-4613-8917-0_1.
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Cifuentes, Arturo O. "Problem 9." In Using MSC/NASTRAN. Springer New York, 1989. http://dx.doi.org/10.1007/978-1-4613-8917-0_10.
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Cifuentes, Arturo O. "Problem 10." In Using MSC/NASTRAN. Springer New York, 1989. http://dx.doi.org/10.1007/978-1-4613-8917-0_11.
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Cifuentes, Arturo O. "Problem 11." In Using MSC/NASTRAN. Springer New York, 1989. http://dx.doi.org/10.1007/978-1-4613-8917-0_12.
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Cifuentes, Arturo O. "Problem 12." In Using MSC/NASTRAN. Springer New York, 1989. http://dx.doi.org/10.1007/978-1-4613-8917-0_13.
Full textConference papers on the topic "MSC"
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Coughlin, Thomas R., Matthew Haugh, Muriel Voisin, Evelyn Birmingham, Laoise M. McNamara, and Glen L. Niebur. "Primary Cilia Knockdown Reduces the Number of Stromal Cells in Three Dimensional Ex Vivo Culture." In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14723.
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Mesenchymal stem cells (MSCs) are multipotent stromal cells that reside in the bone marrow and differentiate into connective cell lines, such as adipocytes and osteoblasts [1]. An appropriate balance of MSC differentiation toward adipocytes and osteoblasts is vital to bone homeostasis [6]. In vitro work demonstrates that differentiation of MSCs is influenced by mechanical stimuli [2, 3]. In a mouse model, the ratio of adipocytes to MSCs in the marrow was 19% lower compared to controls following treatment by low magnitude mechanical signals (LMMS) [4]. In mice, LMMS increased MSC number by 46% and the differentiation capacity of MSCs was biased towards osteoblastic compared to adipogenic differentiation [5]. Thus, mechanobiological stimuli may play an important role in maintaining balanced MSC differentiation.
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Huang, Alice H., and Robert L. Mauck. "Repeated Dynamic Loading Modulates Cartilage Gene Expression but Does Not Improve Mechanical Properties of MSC-Laden Hydrogels." In ASME 2009 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2009. http://dx.doi.org/10.1115/sbc2009-204339.
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Mesenchymal stem cells (MSCs) are a multi-potential cell type that can differentiate toward a variety of tissue-specific phenotypes, including cartilage. Given their chondrogenic potential, MSCs are a promising cell source for cartilage tissue engineering (TE). However, while MSCs readily undergo chondrogenesis in 3D culture and deposit a cartilage-like matrix, the mechanical properties of MSC-seeded constructs are greatly inferior to chondrocyte-seeded constructs similarly maintained [1]. To date, optimization strategies for enhancing functional MSC chondrogenesis, including increasing seeding density and transient application of growth factor, have shown limited success [3]. Using microarray analysis, we have recently demonstrated that mis-expression of certain genes, including lubricin, chondromodulin and RGD-CAP, a collagen associated protein, may underlie this disparity in mechanical function [2]. In this study, we examined dynamic compression as an alternative method to enhance MSC differentiation. Previous work using chondrocyte-based constructs have demonstrated that matrix biosynthesis and mechanical properties were improved with the application of cyclic compression [4]. Furthermore, upregulation of lubricin was observed when surface motion was applied to chondrocyte-seeded porous scaffolds [5]. While significant effort has gone toward optimizing loading parameters to direct tissue growth of chondrocyte-based constructs, few studies have examined the effects of mechanical stimulation on MSC-based constructs. Some have demonstrated positive effects on MSC chondrogenesis with application of compressive loading [6, 7], while others have shown that long-term loading may adversely affect the developing mechanical properties of MSC-seeded constructs [8]. In this study, we examined the effects of repeated dynamic compressive loading on MSC chondrogenesis and showed that mechanical properties and gene expression were modulated by this loading modality.
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Wingate, Kathryn, Yan Tan, and Wei Tan. "The Effects of Mechanical and Chemical Stimuli on Mesenchymal Stem Cell Vascular Trans-Differentiation and Paracrine Signaling." In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14742.
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Mesenchymal Stem Cells (MSCs) show great promise for the treatment of cardiovascular diseases by tissue engineering and cell therapy. MSCs are particularly useful for vascular therapies as they are easily obtainable, allogenic, trans-differentiate into specific vascular cells, and assist in regenerating vascular tissue through paracrine signaling. [1] However, the mechanisms which direct MSC trans-differentiation and paracrine signaling are not well defined. [2] Incorrect differentiation of MSC can lead to catastrophic side effects such as the development of a dysfunctional endothelium. [3] To safely utilize these cells for the treatment of vascular diseases it is critical to understand the underlying mechanisms that direct MSC differentiation and paracrine signaling.
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Barminko, Jeffrey, Jean Pierre Dolle, Rene Schloss, Martin Grumet, and Martin L. Yarmush. "Encapsulated Mesenchymal Stem Cells for Central Nervous System Repair." In ASME 2010 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2010. http://dx.doi.org/10.1115/sbc2010-19712.
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Mesenchymal stromal cells (MSC) have long been regarded as a cell source with the potential to provide therapies for various different tissue pathologies. They were originally identified for their ability to adhere to tissue culture plastic and gained favor due to their tremendous ability to propagate[1]. It was this finding as well as their ability to differentiate into lineages of mesoderm which have long made MSC a potential tool for autologous cellular replacement therapies [2, 3]. More recently, their cyto-protective role has been realized and been implicated in the benefit achieved in treating various different tissue pathologies. MSC have been found to secrete several different cytokines and growth factors in vitro. Furthermore, these factors can be modulated based on the environment MSC are exposed to. MSC have shown therapeutic benefits in models of GVHD, myocardial infarction, fulminant hepatic failure, central nervous system trauma and others, without any apparent cellular replacement. These advances propelled MSC to the fore front of potential cellular therapies and many are seeking to take advantage of their tissue protective properties. However, several draw backs in current methods of MSC implantation limit the ability to carry out safe and controlled clinical trials. Limitation with current MSC implantation approaches include; 1) directly transplanted MSCs exposed to the complex injury environment may be affected themselves early in the treatment processes, 2) MSC may also migrate to undesired tissue locations and 3) may differentiate into undesired end stage cells. These issues severally limit the translatability of MSC treatments in clinical settings; they make controlling experiments very difficult. There becomes a need to develop engineered methods for delivering these cells in a controlled manner. In order to circumvent these potential problems, we propose to use an alginate microencapsulation system as a vehicle for MSC delivery taking advantage of the soluble factors MSC provide.
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Metzger, Thomas A., Stephen A. Schwaner, and Glen L. Niebur. "Pressure Gradients in the Trabecular Pore Space of Femurs During Physiologic Loading." In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14433.
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Bone marrow is an important niche for mesenchymal stromal cells (MSCs), which are progenitors for connective tissue cells. MSCs respond to mechanical stimuli (1). For example, steady and oscillatory fluid flow both affect MSC differentiation to the osteogenic lineages (2), while hydrostatic pressure increases MSC osteogenic protein expression (3). Both pressure and fluid flow are induced in bone marrow during loading due to the poroelastic nature of trabecular bone, and these may affect the differentiation or proliferation of the resident stromal cells.
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Huang, Alice H., and Robert L. Mauck. "Extended Long-Term Culture of MSC-Laden Agarose Constructs Does Not Produce Functional Tissue Comparable to Primary Chondrocytes." In ASME 2010 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2010. http://dx.doi.org/10.1115/sbc2010-19643.
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Articular cartilage lines the surfaces of joints and transmits the forces arising from locomotion. The poor ability of cartilage to self-repair has motivated efforts to engineer replacements that recapitulate this load-bearing function. While chondrocyte-laden constructs have been generated with near-native mechanical properties, limitations in chondrocyte availability may preclude their clinical use. Therefore, mesenchymal stem cells (MSCs), which can undergo chondrogenesis in 3D culture, have emerged as a promising alternative [1]. However, although MSCs deposit a cartilaginous matrix, mechanical and biochemical properties are lower than those achieved with chondrocytes [1, 2]. Using microarray analysis, we recently showed that limitations in functional MSC chondrogenesis may stem from incomplete or incorrect molecular induction; molecular differences were observed between donor-matched differentiated chondrocytes and newly differentiated MSCs over 8 weeks of culture [2]. While some genes remained consistently low in MSCs compared to chondrocytes, others gradually increased with time, approaching chondrocyte levels by 8 weeks. As these molecules may underlie the functional disparity between chondrocytes and MSCs, we hypothesized that longer culture durations may improve MSC-seeded construct properties and chondrogenesis. To test this hypothesis, we characterized the evolution of functional properties of MSC- and chondrocyte-seeded constructs over 4 months of in vitro culture in pro-chondrogenic medium.
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Kulebyakina, M. A., D. A. Butuzova, N. D. Basalova, and A. Yu Efimenko. "DKK3 SECRETED BY MESENCHYMAL STROMAL CELLS PREVENTS FIBROBLAST-TO-MYOFIBROBLAST TRANSITION." In XI МЕЖДУНАРОДНАЯ КОНФЕРЕНЦИЯ МОЛОДЫХ УЧЕНЫХ: БИОИНФОРМАТИКОВ, БИОТЕХНОЛОГОВ, БИОФИЗИКОВ, ВИРУСОЛОГОВ, МОЛЕКУЛЯРНЫХ БИОЛОГОВ И СПЕЦИАЛИСТОВ ФУНДАМЕНТАЛЬНОЙ МЕДИЦИНЫ. IPC NSU, 2024. https://doi.org/10.25205/978-5-4437-1691-6-287.
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It is well known that mesenchymal stromal cells (MSCs) prevent the development of fibrosis in a paracrine manner; still, the underlying mechanisms have not yet been studied. Using proteomic analysis, we identified the DKK3 protein, a regulator of the Wnt signaling pathway, in the MSC secretome. We also demonstrated that the DKK3 protein in the MSC secretome suppresses the canonical Wnt signaling pathway in fibroblasts and prevents myofibroblast differentiation.
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Farrell, Megan J., John Shin, and Robert L. Mauck. "Functional Consequences of Glucose and Oxygen Deprivation in Engineered MSC-Based Cartilage Constructs." In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14495.
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Clinical implementation of stem cell-based cartilage repair techniques has been limited by the inability of these cells to produce cartilaginous tissue equivalent to that produced by native chondrocytes. We have recently shown that while bulk mechanical properties of mesenchymal stem cell (MSC)-laden constructs are lower than chondrocyte-laden constructs, MSCs can in fact produce tissue that matches or exceeds the biochemical and mechanical properties produced by chondrocytes in regions where there is maximal nutrient supply [1]. We also noted that in the central regions of constructs, where nutrient and oxygen availability is lowest (due to consumption through the construct depth), MSC viability was markedly lower than in the outer regions and drastically lower than the center of chondrocyte-laden constructs maintained similarly. These data suggest that MSCs can achieve a high anabolic functionality when they undergo chondrogenesis (via the provision of TGF-β3) and in doing so can produce tissue of equivalent or greater properties than chondrocytes. However, unlike chondrocytes, MSCs appear thrive only when they are provided with a sufficient nutrient supply. To further delineate the role of microenvironmental stressors [2, 3, 4] on MSC viability and functional capacity, we evaluated the impact of glucose and oxygen deprivation, in the presence and absence of TGF-β, during long term culture. Furthermore, since MSC isolation procedures result in a heterogeneous cell population [5,6], we investigated whether different clonal populations respond to these microenvironmental stressors in a distinct fashion.
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Kim, Minwook, Jason A. Burdick, and Robert L. Mauck. "Influence of Chondrocyte Zone on Co-Cultures With Mesenchymal Stem Cells in HA Hydrogels for Cartilage Tissue Engineering." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80859.
Full textAbstract:
Mesenchymal stem cells (MSCs) are an attractive cell type for cartilage tissue engineering in that they can undergo chondrogenesis in a variety of 3D contexts [1]. Focused efforts in MSC-based cartilage tissue engineering have recently culminated in the formation of biologic materials possessing biochemical and functional mechanical properties that match that of the native tissue [2]. These approaches generally involve the continuous or intermittent application of pro-chondrogenic growth factors during in vitro culture. For example, in one recent study, we showed robust construct maturation in MSC-seeded hyaluronic acid (HA) hydrogels transiently exposed to high levels of TGF-β3 [3]. Despite the promise of this approach, MSCs are a multipotent cell type and retain a predilection towards hypertrophic phenotypic conversion (i.e., bone formation) when removed from a pro-chondrogenic environment (e.g., in vivo implantation). Indeed, even in a chondrogenic environment, many MSC-based cultures express pre-hypertrophic markers, including type X collagen, MMP13, and alkaline phosphatase [4]. To address this issue, recent studies have investigated co-culture of human articular chondrocytes and MSCs in both pellet and hydrogel environments. Chondrocytes appear to enhance the initial efficiency of MSC chondrogenic conversion, as well as limit hypertrophic changes in some instances (potentially via secretion of PTHrP and/or other factors) [5–7]. While these findings are intriguing, articular cartilage has a unique depth-dependent morphology including zonal differences in chondrocyte identity. Ng et al. showed that zonal chondrocytes seeded in a bi-layered agarose hydrogel construct can recreate depth-dependent cellular and mechanical heterogeneity, suggesting that these identities are retained with transfer to 3D culture systems [8]. Further, Cheng et al. showed that differences in matrix accumulation and hypertrophy in zonal chondrocytes was controlled by bone morphogenic protein [9]. To determine whether differences in zonal chondrocyte identity influences MSC fate decisions, we evaluated functional properties and phenotypic stability in photocrosslinked hyaluronic acid (HA) hydrogels using distinct, zonal chondrocyte cell fractions co-cultured with bone marrow derived MSCs.
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Wingate, Kathryn, Yan Tan, Raphael Nemenoff, and Wei Tan. "Combined Effects of Nanofiber Matrix Elasticity and VEGF-A on the Differentiation of Mesenchymal Stem Cells Towards Mature Endothelial Cells." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80747.
Full textAbstract:
The potential of mesenchymal stem cell (MSC) in the treatment of vascular diseases is becoming increasingly recognized.[1] The use of MSC to produce a functional endothelium in synthetic vascular grafts is of particular interest as this would prevent common graft failures such as neointima hyperplasia and thrombus. Current attempts to produce a functional endothelial layer with endothelial cells (EC) have limited success due to the need for invasive surgery and the limited expansion capability these cells have in vitro.[2] MSC are a powerful cellular alternative as they are easily obtained through a bone marrow biopsy, have a large expansion capability in vitro, are multipotent, and thromboresistant. Individual factors such as matrix elasticity, matrix structure, growth factors, and mechanical stimulations have all been shown to contribute to MSC differentiation towards vascular phenotypes in vivo. However, the response of MSCs to the combined effects of these factors is not well characterized. Additionally, many experiments studying MSC differentiation are conducted on 2D substrates instead of simulating the 3D nanofiber matrix structure found in-vivo. Furthermore, little is known about the underlying cell signaling pathways that direct vascular differentiation. Currently, researchers have yet to achieve MSC differentiation into mature, functional endothelial cells, a critical step for regenerating healthy vascular tissue. We hypothesize that the combined effects of VEGF-A growth factor and a 3D matrix elasticity that mimicking the mechanochemical properties of in-vivo intima induce more complete MSC differentiation into EC expressing mature markers through the regulation of critical vascular signaling molecules such as MAPK/ERK and RhoA/Rock.
Reports on the topic "MSC"
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Herman, Michal, and Kawano Toshihiko. Problem with gradual absorption in MSD/MSC calculations. Office of Scientific and Technical Information (OSTI), 2023. http://dx.doi.org/10.2172/2377303.
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Carr, Randolf, and Nicole Koenig. Debrief MSC 2024. Munich Security Conference, 2024. http://dx.doi.org/10.47342/hiqv3321.
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Carr, Randolf, and Nicole Koenig. Debrief MSC 2024 German Version. Munich Security Conference, 2024. http://dx.doi.org/10.47342/ixxf9801.
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Hawley, Daniel P. Command and Control of MSC Shipping. Defense Technical Information Center, 1996. http://dx.doi.org/10.21236/ada307349.
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S. Drummond. CASK/MSC/WP PREPARATION SYSTEM DESCRIPTION DOCUMENT. Office of Scientific and Technical Information (OSTI), 2005. http://dx.doi.org/10.2172/841281.
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Cörvers, Frank, Arnold Hendrikse, and Sanne Steens. Macrodoelmatigheid MSc Crop Biotechnology and Engineering (CBE). ROA, 2022. http://dx.doi.org/10.26481/umarot.2022002.
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Zarrieß, Benjamin, and Anni-Yasmin Turhan. Most Specific Generalizations w.r.t. General EL-TBoxes. Technische Universität Dresden, 2013. http://dx.doi.org/10.25368/2022.196.
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In the area of Description Logics the least common subsumer (lcs) and the most specific concept (msc) are inferences that generalize a set of concepts or an individual, respectively, into a single concept. If computed w.r.t. a general EL-TBox neither the lcs nor the msc need to exist. So far in this setting no exact conditions for the existence of lcs- or msc-concepts are known. This report provides necessary and suffcient conditions for the existence of these two kinds of concepts. For the lcs of a fixed number of concepts and the msc we show decidability of the existence in PTime and polynomial bounds on the maximal roledepth of the lcs- and msc-concepts. The latter allows to compute the lcs and the msc, respectively.
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Hua, Zi Bo, and Lv Yuan Chen. Human UCB MSC versus placebo for effect on kidney fibrosis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, 2022. http://dx.doi.org/10.37766/inplasy2022.10.0104.
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Review question / Objective: Human UCB MSC versus placebo for effect on kidney fibrosis Condition being studied: Renal fibrosis is the final outcome of long-term chronic kidney disease, and the kidney will lose its basic function. This experiment will explore the effect of Human UCB MSC for effect on kidney fibrosis. Main outcome(s): Correlation analysis of Human UCB MSC treatment on renalfibrosis.
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Küsters, Ralf, and Ralf Molitor. Computing Most Specific Concepts in Description Logics with Existential Restrictions. Aachen University of Technology, 2000. http://dx.doi.org/10.25368/2022.108.
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Computing the most specific concept (msc) is an inference task that can be used to support the 'bottom-up' construction of knowledge bases for KR systems based on description logics. For description logics that allow for number restrictions or existential restrictions, the msc need not exist, though. Previous work on this problem has concentrated on description logics that allow for universal value restrictions and number restrictions, but not for existential restrictions. The main new contribution of this paper is the treatment of description logics with existential restrictions. More precisely, we show that, for the description logic ALE (which allows for conjunction, universal value restrictions, existential restrictions, negation of atomic concepts) the msc of an ABox-individual only exists in case of acyclic ABoxes. For cyclic ABoxes, we show how to compute an approximation of the msc. Our approach for computing the (approximation of the) msc is based on representing concept descriptions by certain trees and ABoxes by certain graphs, and then characterizing instance relationships by homomorphisms from trees into graphs. The msc/approximation operation then mainly corresponds to unraveling the graphs into trees and translating them back into concept descriptions.
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Shoales, Gregory A., and Scott A. Fawaz. Stress Concentration Factor Determination for Various Tensile Test Specimen Configuration by the Finite Element Method Using MSC/PATRAN and MSC/NASTRAN. Defense Technical Information Center, 2004. http://dx.doi.org/10.21236/ada430477.
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