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Journal articles on the topic 'Human pluripotent stem cells (hPSC)'

Author: Grafiati

Published: 4 June 2021

Last updated: 8 February 2022

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1

Hayashi, Yohei, and Miho Kusuda Furue. "Biological Effects of Culture Substrates on Human Pluripotent Stem Cells." Stem Cells International 2016 (2016): 1–11. http://dx.doi.org/10.1155/2016/5380560.

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In recent years, as human pluripotent stem cells (hPSCs) have been commonly cultured in feeder-free conditions, a number of cell culture substrates have been applied or developed. However, the functional roles of these substrates in maintaining hPSC self-renewal remain unclear. Here in this review, we summarize the types of these substrates and their effect on maintaining hPSC self-renewal. Endogenous extracellular matrix (ECM) protein expression has been shown to be crucial in maintaining hPSC self-renewal. These ECM molecules interact with integrin cell-surface receptors and transmit their c

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Maysubara, Hiroyuki, Akira Niwa, Tatsutoshi Nakahata, and Megumu K. Saito. "NK Cells from Human Pluripotent Stem Cells for Immunotherapy." Blood 132, Supplement 1 (2018): 4955. http://dx.doi.org/10.1182/blood-2018-99-115499.

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Abstract Natural Killer (NK) cells are a one of innate lymphocytes and show cytotoxicity against tumour cells without prior antigen specific stimulation. . NK cells can demonstrate stronger cytotoxicity than T cells in the absence of MHC Class I, and survive short lifespan from several weeks to one month. It suggested that NK cells show low risk of cytokine long-term secretion inside patient's body. Previous studies have developed peripheral blood mononuclear cells (PBMC) derived NK cells expansions or NK cells differentiation from cord blood (CB) cells for immunotherapy. Expansion trial using

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3

Wei, Yanxing, Tianyu Wang, Lishi Ma, et al. "Efficient derivation of human trophoblast stem cells from primed pluripotent stem cells." Science Advances 7, no. 33 (2021): eabf4416. http://dx.doi.org/10.1126/sciadv.abf4416.

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Human trophoblast stem cells (hTSCs) provide a valuable model to study placental development and function. While primary hTSCs have been derived from embryos/early placenta, and transdifferentiated hTSCs from naïve human pluripotent stem cells (hPSCs), the generation of hTSCs from primed PSCs is problematic. We report the successful generation of TSCs from primed hPSCs and show that BMP4 substantially enhances this process. TSCs derived from primed hPSCs are similar to blastocyst-derived hTSCs in terms of morphology, proliferation, differentiation potential, and gene expression. We define the

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Lipsitz, Yonatan Y., Curtis Woodford, Ting Yin, Jacob H. Hanna, and Peter W. Zandstra. "Modulating cell state to enhance suspension expansion of human pluripotent stem cells." Proceedings of the National Academy of Sciences 115, no. 25 (2018): 6369–74. http://dx.doi.org/10.1073/pnas.1714099115.

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The development of cell-based therapies to replace missing or damaged tissues within the body or generate cells with a unique biological activity requires a reliable and accessible source of cells. Human pluripotent stem cells (hPSC) have emerged as a strong candidate cell source capable of extended propagation in vitro and differentiation to clinically relevant cell types. However, the application of hPSC in cell-based therapies requires overcoming yield limitations in large-scale hPSC manufacturing. We explored methods to convert hPSC to alternative states of pluripotency with advantageous b

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Lim, Seakcheng, Rachel A. Shparberg, Jens R. Coorssen, and Michael D. O’Connor. "Application of the RBBP9 Serine Hydrolase Inhibitor, ML114, Decouples Human Pluripotent Stem Cell Proliferation and Differentiation." International Journal of Molecular Sciences 21, no. 23 (2020): 8983. http://dx.doi.org/10.3390/ijms21238983.

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Retinoblastoma binding protein 9 (RBBP9) is required for maintaining the expression of both pluripotency and cell cycle genes in human pluripotent stem cells (hPSCs). An siRNA-based study from our group showed it does so by influencing cell cycle progression through the RB/E2F pathway. In non-pluripotent cells, RBBP9 is also known to have serine hydrolase (SH) activity, acting on currently undefined target proteins. The role of RBBP9 SH activity in hPSCs, and during normal development, is currently unknown. To begin assessing whether RBBP9 SH activity might contribute to hPSC maintenance, hPSC

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Ran, Dan, Wei-Jong Shia, Miao-Chia Lo, et al. "RUNX1a enhances hematopoietic lineage commitment from human embryonic stem cells and inducible pluripotent stem cells." Blood 121, no. 15 (2013): 2882–90. http://dx.doi.org/10.1182/blood-2012-08-451641.

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Abstract Advancements in human pluripotent stem cell (hPSC) research have potential to revolutionize therapeutic transplantation. It has been demonstrated that transcription factors may play key roles in regulating maintenance, expansion, and differentiation of hPSCs. In addition to its regulatory functions in hematopoiesis and blood-related disorders, the transcription factor RUNX1 is also required for the formation of definitive blood stem cells. In this study, we demonstrated that expression of endogenous RUNX1a, an isoform of RUNX1, parallels with lineage commitment and hematopoietic emerg

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7

Nemade, Harshal, Aviseka Acharya, Umesh Chaudhari, et al. "Cyclooxygenases Inhibitors Efficiently Induce Cardiomyogenesis in Human Pluripotent Stem Cells." Cells 9, no. 3 (2020): 554. http://dx.doi.org/10.3390/cells9030554.

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Application of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is limited by the challenges in their efficient differentiation. Recently, the Wingless (Wnt) signaling pathway has emerged as the key regulator of cardiomyogenesis. In this study, we evaluated the effects of cyclooxygenase inhibitors on cardiac differentiation of hPSCs. Cardiac differentiation was performed by adherent monolayer based method using 4 hPSC lines (HES3, H9, IMR90, and ES4SKIN). The efficiency of cardiac differentiation was evaluated by flow cytometry and RT-qPCR. Generated hPSC-CMs were characterised us

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Karam, Manale, Ihab Younis, Noor R. Elareer, Sara Nasser, and Essam M. Abdelalim. "Scalable Generation of Mesenchymal Stem Cells and Adipocytes from Human Pluripotent Stem Cells." Cells 9, no. 3 (2020): 710. http://dx.doi.org/10.3390/cells9030710.

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Human pluripotent stem cells (hPSCs) can provide unlimited supply for mesenchymal stem cells (MSCs) and adipocytes that can be used for therapeutic applications. Here we developed a simple and highly efficient all-trans-retinoic acid (RA)-based method for generating an off-the-shelf and scalable number of human pluripotent stem cell (hPSC)-derived MSCs with enhanced adipogenic potential. We showed that short exposure of multiple hPSC lines (hESCs/hiPSCs) to 10 μM RA dramatically enhances embryoid body (EB) formation through regulation of genes activating signaling pathways associated with cell

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9

Walasek, Marta A., Crystal Chau, Christian Barborini, et al. "A Reproducible and Simple Method to Generate Red Blood Cells from Human Pluripotent Stem Cells." Blood 134, Supplement_1 (2019): 1189. http://dx.doi.org/10.1182/blood-2019-128830.

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Erythroid cells generated from human pluripotent stem cells (hPSCs) can potentially offer an unlimited and safe supply of red blood cells (RBCs) for transfusion. Human PSC-derived erythroid cells at various stages of differentiation can also be used to model blood diseases, test new drug candidates, and develop cellular and genetic therapies. Although several protocols for deriving RBCs from hPSCs have been described, these are typically complex, involving multiple culture steps that may include co-culture with feeder cells, and exhibit large variability in erythroid cell yields between hPSC l

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Rehakova, Daniela, Tereza Souralova, and Irena Koutna. "Clinical-Grade Human Pluripotent Stem Cells for Cell Therapy: Characterization Strategy." International Journal of Molecular Sciences 21, no. 7 (2020): 2435. http://dx.doi.org/10.3390/ijms21072435.

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Human pluripotent stem cells have the potential to change the way in which human diseases are cured. Clinical-grade human embryonic stem cells and human induced pluripotent stem cells have to be created according to current good manufacturing practices and regulations. Quality and safety must be of the highest importance when humans’ lives are at stake. With the rising number of clinical trials, there is a need for a consensus on hPSCs characterization. Here, we summarize mandatory and ′for information only′ characterization methods with release criteria for the establishment of clinical-grade

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Rungsiwiwut, Ruttachuk, Praewphan Ingrungruanglert, Pranee Numchaisrika, Pramuan Virutamasen, Tatsanee Phermthai, and Kamthorn Pruksananonda. "Human Umbilical Cord Blood-Derived Serum for Culturing the Supportive Feeder Cells of Human Pluripotent Stem Cell Lines." Stem Cells International 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/4626048.

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Although human pluripotent stem cells (hPSCs) can proliferate robustly on the feeder-free culture system, genetic instability of hPSCs has been reported in such environment. Alternatively, feeder cells enable hPSCs to maintain their pluripotency. The feeder cells are usually grown in a culture medium containing fetal bovine serum (FBS) prior to coculture with hPSCs. The use of FBS might limit the clinical application of hPSCs. Recently, human cord blood-derived serum (hUCS) showed a positive effect on culture of mesenchymal stem cells. It is interesting to test whether hUCS can be used for cul

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Go, Young-Hyun, Jumee Kim, Ho-Chang Jeong, et al. "Luteolin Induces Selective Cell Death of Human Pluripotent Stem Cells." Biomedicines 8, no. 11 (2020): 453. http://dx.doi.org/10.3390/biomedicines8110453.

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Despite recent advances in clinical stem cell therapy applications based on human pluripotent stem cells (hPSCs), potential teratoma formation due to the presence of residual undifferentiated hPSCs remains a serious risk factor that challenges widespread clinical application. To overcome this risk, a variety of approaches have been developed to eliminate the remaining undifferentiated hPSCs via selective cell death induction. Our study seeks to identify natural flavonoids that are more potent than quercetin (QC), to selectively induce hPSC death. Upon screening in-house flavonoids, luteolin (L

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13

Le, Minh Nguyen Tuyet, and Kouichi Hasegawa. "Expansion Culture of Human Pluripotent Stem Cells and Production of Cardiomyocytes." Bioengineering 6, no. 2 (2019): 48. http://dx.doi.org/10.3390/bioengineering6020048.

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Transplantation of human pluripotent stem cell (hPSCs)-derived cardiomyocytes for the treatment of heart failure is a promising therapy. In order to implement this therapy requiring numerous cardiomyocytes, substantial production of hPSCs followed by cardiac differentiation seems practical. Conventional methods of culturing hPSCs involve using a 2D culture monolayer that hinders the expansion of hPSCs, thereby limiting their productivity. Advanced culture of hPSCs in 3D aggregates in the suspension overcomes the limitations of 2D culture and attracts immense attention. Although the hPSC produc

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14

Roberts, R. Michael, Kyle M. Loh, Mitsuyoshi Amita, et al. "Differentiation of trophoblast cells from human embryonic stem cells: to be or not to be?" REPRODUCTION 147, no. 5 (2014): D1—D12. http://dx.doi.org/10.1530/rep-14-0080.

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It is imperative to unveil the full range of differentiated cell types into which human pluripotent stem cells (hPSCs) can develop. The need is twofold: it will delimit the therapeutic utility of these stem cells and is necessary to place their position accurately in the developmental hierarchy of lineage potential. Accumulated evidence suggested that hPSC could develop in vitro into an extraembryonic lineage (trophoblast (TB)) that is typically inaccessible to pluripotent embryonic cells during embryogenesis. However, whether these differentiated cells are truly authentic TB has been challeng

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15

Dick, Emily, Divya Rajamohan, Jonathon Ronksley, and Chris Denning. "Evaluating the utility of cardiomyocytes from human pluripotent stem cells for drug screening." Biochemical Society Transactions 38, no. 4 (2010): 1037–45. http://dx.doi.org/10.1042/bst0381037.

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Functional cardiomyocytes can now be derived routinely from hPSCs (human pluripotent stem cells), which collectively include embryonic and induced pluripotent stem cells. This technology presents new opportunities to develop pharmacologically relevant in vitro screens to detect cardiotoxicity, with a view to improving patient safety while reducing the economic burden to industry arising from high drug attrition rates. In the present article, we consider the need for human cardiomyocytes in drug-screening campaigns and review the strategies used to differentiate hPSCs towards the cardiac lineag

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Ghosheh, Nidal, Barbara Küppers-Munther, Annika Asplund, et al. "Comparative transcriptomics of hepatic differentiation of human pluripotent stem cells and adult human liver tissue." Physiological Genomics 49, no. 8 (2017): 430–46. http://dx.doi.org/10.1152/physiolgenomics.00007.2017.

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Hepatocytes derived from human pluripotent stem cells (hPSC-HEP) have the potential to replace presently used hepatocyte sources applied in liver disease treatment and models of drug discovery and development. Established hepatocyte differentiation protocols are effective and generate hepatocytes, which recapitulate some key features of their in vivo counterparts. However, generating mature hPSC-HEP remains a challenge. In this study, we applied transcriptomics to investigate the progress of in vitro hepatic differentiation of hPSCs at the developmental stages, definitive endoderm, hepatoblast

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Nii, Takenobu, Hiroshi Kohara, Tomotoshi Marumoto, Tetsushi Sakuma, Takashi Yamamoto, and Kenzaburo Tani. "Single-Cell-State Culture of Human Pluripotent Stem Cells Increases Transfection Efficiency." Blood 126, no. 23 (2015): 2037. http://dx.doi.org/10.1182/blood.v126.23.2037.2037.

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Abstract Human pluripotent stem cells (hPSCs), such as human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), have the potential to self-renew indefinitely and differentiate into various cell types. hPSCs can differentiate into various stem or progenitor cell populations used for regenerative medicine and drug development. Newly developed genome editing technology has advanced the use of hPSCs for such purposes. However, to fully utilize hPSCs to achieve this goal, more efficient gene transfer methods under defined conditions are required. Development of efficien

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18

Lees, Jarmon G., Timothy S. Cliff, Amanda Gammilonghi, et al. "Oxygen Regulates Human Pluripotent Stem Cell Metabolic Flux." Stem Cells International 2019 (May 19, 2019): 1–17. http://dx.doi.org/10.1155/2019/8195614.

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Metabolism has been shown to alter cell fate in human pluripotent stem cells (hPSC). However, current understanding is almost exclusively based on work performed at 20% oxygen (air), with very few studies reporting on hPSC at physiological oxygen (5%). In this study, we integrated metabolic, transcriptomic, and epigenetic data to elucidate the impact of oxygen on hPSC. Using 13C-glucose labeling, we show that 5% oxygen increased the intracellular levels of glycolytic intermediates, glycogen, and the antioxidant response in hPSC. In contrast, 20% oxygen increased metabolite flux through the TCA

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Pavarajarn, Wipawee, Ruttachuk Rungsiwiwut, Pranee Numchaisrika, Pramuan Virutamasen, and Kamthorn Pruksananonda. "Human Caesarean scar-derived feeder cells: a novel feeder cell type for culturing human pluripotent stem cells without exogenous basic fibroblast growth factor supplementation." Reproduction, Fertility and Development 32, no. 9 (2020): 822. http://dx.doi.org/10.1071/rd19128.

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In a feeder-dependent culture system of human pluripotent stem cells (hPSCs), coculture with mouse embryonic fibroblasts may limit the clinical use of hPSCs. The aim of this study was to determine the feasibility of using human Caesarean scar fibroblasts (HSFs) as feeder cells for the culture of hPSCs. HSFs were isolated and characterised and cocultured with hPSCs, and the pluripotency, differentiation ability and karyotypic stability of hPSCs were determined. Inactivated HSFs expressed genes (including inhibin subunit beta A (INHBA), bone morphogenetic protein 4 (BMP4), fibroblast growth fact

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Butts, Jessica C., Dylan A. McCreedy, Jorge Alexis Martinez-Vargas, et al. "Differentiation of V2a interneurons from human pluripotent stem cells." Proceedings of the National Academy of Sciences 114, no. 19 (2017): 4969–74. http://dx.doi.org/10.1073/pnas.1608254114.

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The spinal cord consists of multiple neuronal cell types that are critical to motor control and arise from distinct progenitor domains in the developing neural tube. Excitatory V2a interneurons in particular are an integral component of central pattern generators that control respiration and locomotion; however, the lack of a robust source of human V2a interneurons limits the ability to molecularly profile these cells and examine their therapeutic potential to treat spinal cord injury (SCI). Here, we report the directed differentiation of CHX10+ V2a interneurons from human pluripotent stem cel

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Wang, Zongjie, Mark Gagliardi, Reza M. Mohamadi, et al. "Ultrasensitive and rapid quantification of rare tumorigenic stem cells in hPSC-derived cardiomyocyte populations." Science Advances 6, no. 12 (2020): eaay7629. http://dx.doi.org/10.1126/sciadv.aay7629.

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The ability to detect rare human pluripotent stem cells (hPSCs) in differentiated populations is critical for safeguarding the clinical translation of cell therapy, as these undifferentiated cells have the capacity to form teratomas in vivo. The detection of hPSCs must be performed using an approach compatible with traceable manufacturing of therapeutic cell products. Here, we report a novel microfluidic approach, stem cell quantitative cytometry (SCQC), for the quantification of rare hPSCs in hPSC-derived cardiomyocyte (CM) populations. This approach enables the ultrasensitive capture, profil

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Hu, Zhixing, Hanqin Li, Houbo Jiang, et al. "Transient inhibition of mTOR in human pluripotent stem cells enables robust formation of mouse-human chimeric embryos." Science Advances 6, no. 20 (2020): eaaz0298. http://dx.doi.org/10.1126/sciadv.aaz0298.

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It has not been possible to generate naïve human pluripotent stem cells (hPSCs) that substantially contribute to mouse embryos. We found that a brief inhibition of mTOR with Torin1 converted hPSCs from primed to naïve pluripotency. The naïve hPSCs were maintained in the same condition as mouse embryonic stem cells and exhibited high clonogenicity, rapid proliferation, mitochondrial respiration, X chromosome reactivation, DNA hypomethylation, and transcriptomes sharing similarities to those of human blastocysts. When transferred to mouse blastocysts, naïve hPSCs generated 0.1 to 4% human cells,

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Goldsteen, Pien A., Christina Yoseif, Amalia M. Dolga, and Reinoud Gosens. "Human pluripotent stem cells for the modelling and treatment of respiratory diseases." European Respiratory Review 30, no. 161 (2021): 210042. http://dx.doi.org/10.1183/16000617.0042-2021.

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Respiratory diseases are among the leading causes of morbidity and mortality worldwide, representing a major unmet medical need. New chemical entities rarely make it into the clinic to treat respiratory diseases, which is partially due to a lack of adequate predictive disease models and the limited availability of human lung tissues to model respiratory disease. Human pluripotent stem cells (hPSCs) may help fill this gap by serving as a scalable human in vitro model. In addition, human in vitro models of rare genetic mutations can be generated using hPSCs. hPSC-derived epithelial cells and org

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Buchholz, David E., Thomas S. Carroll, Arif Kocabas, et al. "Novel genetic features of human and mouse Purkinje cell differentiation defined by comparative transcriptomics." Proceedings of the National Academy of Sciences 117, no. 26 (2020): 15085–95. http://dx.doi.org/10.1073/pnas.2000102117.

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Comparative transcriptomics between differentiating human pluripotent stem cells (hPSCs) and developing mouse neurons offers a powerful approach to compare genetic and epigenetic pathways in human and mouse neurons. To analyze human Purkinje cell (PC) differentiation, we optimized a protocol to generate human pluripotent stem cell-derived Purkinje cells (hPSC-PCs) that formed synapses when cultured with mouse cerebellar glia and granule cells and fired large calcium currents, measured with the genetically encoded calcium indicator jRGECO1a. To directly compare global gene expression of hPSC-PC

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Verma, Vinod, A. Mehta, and S. J. S. Flora. "Human Pluripotent Stem Cells and Drug Discovery: A New Beginning." Defence Life Science Journal 1, no. 1 (2016): 27. http://dx.doi.org/10.14429/dlsj.1.10060.

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Human pluripotent stem cells (hPSCs) offer unique opportunities to discover and develop a new generation of drugs. Their ability to differentiate into virtually any cell type renders them a cost-effective, renewable source of tissue-specific cell types capable of predicting human responses towards novel chemical entities. Using these improved in vitro models based on physiologically relevant human cell types could result in identifying highly precise and safe compounds, thereby reducing drug attrition rates. Moreover, ability to develop humanised disease models for patient-stratified drug scre

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Park, Sang-Wook, Young Jun Koh, Jongwook Jeon, et al. "Efficient differentiation of human pluripotent stem cells into functional CD34+ progenitor cells by combined modulation of the MEK/ERK and BMP4 signaling pathways." Blood 116, no. 25 (2010): 5762–72. http://dx.doi.org/10.1182/blood-2010-04-280719.

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Abstract Differentiation of human pluripotent stem cells (hPSCs) into functional cell types is a crucial step in cell therapy. In the present study, we demonstrate that functional CD34+ progenitor cells can be efficiently produced from human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) by combined modulation of 2 signaling pathways. A higher proportion of CD34+ cells (∼ 20%) could be derived from hPSCs by inhibition of mitogen-activated protein kinase (MAPK) extracellular signal-regulated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling and

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Lin, Xiying, Jiayu Tang, and Yan-Ru Lou. "Human Pluripotent Stem-Cell-Derived Models as a Missing Link in Drug Discovery and Development." Pharmaceuticals 14, no. 6 (2021): 525. http://dx.doi.org/10.3390/ph14060525.

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Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs), have the potential to accelerate the drug discovery and development process. In this review, by analyzing each stage of the drug discovery and development process, we identified the active role of hPSC-derived in vitro models in phenotypic screening, target-based screening, target validation, toxicology evaluation, precision medicine, clinical trial in a dish, and post-clinical studies. Patient-derived or genome-edited PSCs can generate valid in vitro models for

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Jongkamonwiwat, Nopporn, and Parinya Noisa. "Biomedical and Clinical Promises of Human Pluripotent Stem Cells for Neurological Disorders." BioMed Research International 2013 (2013): 1–10. http://dx.doi.org/10.1155/2013/656531.

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Neurological disorders are characterized by the chronic and progressive loss of neuronal structures and functions. There is a variability of the onsets and causes of clinical manifestations. Cell therapy has brought a new concept to overcome brain diseases, but the advancement of this therapy is limited by the demands of specialized neurons. Human pluripotent stem cells (hPSCs) have been promised as a renewable resource for generating human neurons for both laboratory and clinical purposes. By the modulations of appropriate signalling pathways, desired neuron subtypes can be obtained, and indu

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Yang, Hui, Weiyi Zhong, Mohammad Rafi Hamidi, Gaojun Zhou, and Chen Liu. "Functional improvement and maturation of human cardiomyocytes derived from human pluripotent stem cells by barbaloin preconditioning." Acta Biochimica et Biophysica Sinica 51, no. 10 (2019): 1041–48. http://dx.doi.org/10.1093/abbs/gmz090.

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Abstract The development of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is a significant advancement in our ability to obtain cardiomyocytes in vitro for regenerative therapies and drug discovery. However, hPSC-CMs obtained via existing protocols usually exhibit a markedly immature phenotype, compared with adult cardiomyocytes, thereby limiting their application. Here we report that barbaloin preconditioning dramatically improves the morphology, structure-related cardiac gene expression, calcium handling, and electrophysiological properties of hPSC-CMs, which means that barba

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Alshawaf, Abdullah J., Ana Antonic, Efstratios Skafidas, Dominic Chi-Hung Ng, and Mirella Dottori. "WDR62 Regulates Early Neural and Glial Progenitor Specification of Human Pluripotent Stem Cells." Stem Cells International 2017 (2017): 1–9. http://dx.doi.org/10.1155/2017/7848932.

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Mutations in WD40-repeat protein 62 (WDR62) are commonly associated with primary microcephaly and other developmental cortical malformations. We used human pluripotent stem cells (hPSC) to examine WDR62 function during human neural differentiation and model early stages of human corticogenesis. Neurospheres lacking WDR62 expression showed decreased expression of intermediate progenitor marker, TBR2, and also glial marker, S100β. In contrast, inhibition of c-Jun N-terminal kinase (JNK) signalling during hPSC neural differentiation induced upregulation of WDR62 with a corresponding increase in n

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McKnight, Cameron L., Yau Chung Low, David A. Elliott, David R. Thorburn, and Ann E. Frazier. "Modelling Mitochondrial Disease in Human Pluripotent Stem Cells: What Have We Learned?" International Journal of Molecular Sciences 22, no. 14 (2021): 7730. http://dx.doi.org/10.3390/ijms22147730.

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Mitochondrial diseases disrupt cellular energy production and are among the most complex group of inherited genetic disorders. Affecting approximately 1 in 5000 live births, they are both clinically and genetically heterogeneous, and can be highly tissue specific, but most often affect cell types with high energy demands in the brain, heart, and kidneys. There are currently no clinically validated treatment options available, despite several agents showing therapeutic promise. However, modelling these disorders is challenging as many non-human models of mitochondrial disease do not completely

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Hazeltine, Laurie B., Chelsey S. Simmons, Max R. Salick, et al. "Effects of Substrate Mechanics on Contractility of Cardiomyocytes Generated from Human Pluripotent Stem Cells." International Journal of Cell Biology 2012 (2012): 1–13. http://dx.doi.org/10.1155/2012/508294.

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Human pluripotent stem cell (hPSC-) derived cardiomyocytes have potential applications in drug discovery, toxicity testing, developmental studies, and regenerative medicine. Before these cells can be reliably utilized, characterization of their functionality is required to establish their similarity to native cardiomyocytes. We tracked fluorescent beads embedded in 4.4–99.7 kPa polyacrylamide hydrogels beneath contracting neonatal rat cardiomyocytes and cardiomyocytes generated from hPSCs via growth-factor-induced directed differentiation to measure contractile output in response to changes in

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Dakhore, Sushrut, Bhavana Nayer, and Kouichi Hasegawa. "Human Pluripotent Stem Cell Culture: Current Status, Challenges, and Advancement." Stem Cells International 2018 (November 22, 2018): 1–17. http://dx.doi.org/10.1155/2018/7396905.

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Over the past two decades, human embryonic stem cells (hESCs) have gained attention due to their pluripotent and proliferative ability which enables production of almost all cell types in the human body in vitro and makes them an excellent tool to study human embryogenesis and disease, as well as for drug discovery and cell transplantation therapies. Discovery of human-induced pluripotent stem cells (hiPSCs) further expanded therapeutic applications of human pluripotent stem cells (PSCs). hPSCs provide a stable and unlimited original cell source for producing suitable cells and tissues for dow

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Luff, Stephanie A., J. Philip Creamer, Carissa Dege, et al. "Generation of Retinoic Acid-Dependent Definitive Hematopoietic Progenitors from Human Pluripotent Stem Cells." Blood 136, Supplement 1 (2020): 35. http://dx.doi.org/10.1182/blood-2020-142468.

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The generation of the hematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) is a major goal for regenerative medicine. In the embryo, HSCs derive from a HOXA+ population known as hemogenic endothelium (HE) in a retinoic acid (RA)-dependent manner. Using hPSCs, we have previously identified a KDR+CD235a− mesodermal population that gives rise to a clonally multipotent HOXA+ definitive HE. However, this HE lacks HSC-like capacity in the absence of exogenous transgenes and is functionally unresponsive to RA treatment. Thus, the specification of an RA-dependent hematopoietic pro

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Li, Sen, Wendy Keung, Heping Cheng, and Ronald A. Li. "Structural and Mechanistic Bases of Nuclear Calcium Signaling in Human Pluripotent Stem Cell-Derived Ventricular Cardiomyocytes." Stem Cells International 2019 (April 1, 2019): 1–17. http://dx.doi.org/10.1155/2019/8765752.

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The loss of nonregenerative, terminally differentiated cardiomyocytes (CMs) due to aging or diseases is generally considered irreversible. Human pluripotent stem cells (hPSCs) can self-renew while maintaining their pluripotency to differentiate into all cell types, including ventricular (V) cardiomyocytes (CMs), to provide a potential unlimited ex vivo source of CMs for heart disease modeling, drug/cardiotoxicity screening, and cell-based therapies. In the human heart, cytosolic Ca2+ signals are well characterized but the contribution of nuclear Ca2+ is essentially unexplored. The present stud

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Zhang, Fengzhi, Hui Qiu, Xiaohui Dong, et al. "Transferrin improved the generation of cardiomyocyte from human pluripotent stem cells for myocardial infarction repair." Journal of Molecular Histology 52, no. 1 (2020): 87–99. http://dx.doi.org/10.1007/s10735-020-09926-0.

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AbstractHuman pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) hold great promise for the repair of the injured heart, but optimal cell production in a fully chemically defined and cost-effective system is essential for the efficacy and safety of cell transplantation therapies. In this study, we provided a simple and efficient strategy for cardiac differentiation from hPSCs and performed functional evaluation in a rat model of myocardial infarction. Using a chemically defined medium including four components, recombinant human albumin, ascorbic acid, human transferrin, and RPMI 1640,

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Matsubara, Hiroyuki, Akira Niwa, Tatsutoshi Nakahata, and Megumu K. Saito. "Induction of Natural Killer Cells from Human Pluripotent Stem Cells Under Chemically Defined Condition." Blood 128, no. 22 (2016): 1345. http://dx.doi.org/10.1182/blood.v128.22.1345.1345.

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Abstract Natural killer (NK) cells have been proposed as a new source for immunotherapies in various malignancies. Previous studies have developed peripheral blood NK cells expansions or NK cells differentiation from cord blood cells. Expansion trial using IL-15 or dasatinib is not sufficient to obtain NK cells with high cytotoxicity. More recently, NK cells induction from human pluripotent stem cells (hPSCs), taking the advantage of their unlimited growth potential, has been reported. Although previous studies regarding hPSC-derived NK cells seems impressive and successful, most systems used

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Jelinkova, Sarka, Petr Fojtik, Aneta Kohutova, et al. "Dystrophin Deficiency Leads to Genomic Instability in Human Pluripotent Stem Cells via NO Synthase-Induced Oxidative Stress." Cells 8, no. 1 (2019): 53. http://dx.doi.org/10.3390/cells8010053.

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Recent data on Duchenne muscular dystrophy (DMD) show myocyte progenitor’s involvement in the disease pathology often leading to the DMD patient’s death. The molecular mechanism underlying stem cell impairment in DMD has not been described. We created dystrophin-deficient human pluripotent stem cell (hPSC) lines by reprogramming cells from two DMD patients, and also by introducing dystrophin mutation into human embryonic stem cells via CRISPR/Cas9. While dystrophin is expressed in healthy hPSC, its deficiency in DMD hPSC lines induces the release of reactive oxygen species (ROS) through dysreg

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Hyakumura, Tomoko, Stuart McDougall, Sue Finch, Karina Needham, Mirella Dottori, and Bryony A. Nayagam. "Organotypic Cocultures of Human Pluripotent Stem Cell Derived-Neurons with Mammalian Inner Ear Hair Cells and Cochlear Nucleus Slices." Stem Cells International 2019 (November 20, 2019): 1–14. http://dx.doi.org/10.1155/2019/8419493.

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Stem cells have been touted as a source of potential replacement neurons for inner ear degeneration for almost two decades now; yet to date, there are few studies describing the use of human pluripotent stem cells (hPSCs) for this purpose. If stem cell therapies are to be used clinically, it is critical to validate the usefulness of hPSC lines in vitro and in vivo. Here, we present the first quantitative evidence that differentiated hPSC-derived neurons that innervate both the inner ear hair cells and cochlear nucleus neurons in coculture, with significantly more new synaptic contacts formed o

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Ghosheh, Nidal, Björn Olsson, Josefina Edsbagge, et al. "Highly Synchronized Expression of Lineage-Specific Genes duringIn VitroHepatic Differentiation of Human Pluripotent Stem Cell Lines." Stem Cells International 2016 (2016): 1–22. http://dx.doi.org/10.1155/2016/8648356.

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Human pluripotent stem cells- (hPSCs-) derived hepatocytes have the potential to replace many hepatic models in drug discovery and provide a cell source for regenerative medicine applications. However, the generation of fully functional hPSC-derived hepatocytes is still a challenge. Towards gaining better understanding of the differentiation and maturation process, we employed a standardized protocol to differentiate six hPSC lines into hepatocytes and investigated the synchronicity of the hPSC lines by applying RT-qPCR to assess the expression of lineage-specific genes (OCT4, NANOG, T, SOX17,

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Pan, Fong Cheng, Todd Evans, and Shuibing Chen. "Modeling endodermal organ development and diseases using human pluripotent stem cell-derived organoids." Journal of Molecular Cell Biology 12, no. 8 (2020): 580–92. http://dx.doi.org/10.1093/jmcb/mjaa031.

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Abstract Recent advances in development of protocols for directed differentiation from human pluripotent stem cells (hPSCs) to defined lineages, in combination with 3D organoid technology, have facilitated the generation of various endoderm-derived organoids for in vitro modeling of human gastrointestinal development and associated diseases. In this review, we discuss current state-of-the-art strategies for generating hPSC-derived endodermal organoids including stomach, liver, pancreatic, small intestine, and colonic organoids. We also review the advantages of using this system to model variou

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Pandey, Puspa R., Amarel Tomney, Marites T. Woon, et al. "End-to-End Platform for Human Pluripotent Stem Cell Manufacturing." International Journal of Molecular Sciences 21, no. 1 (2019): 89. http://dx.doi.org/10.3390/ijms21010089.

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Industrialization of stem-cell based therapies requires innovative solutions to close the gap between research and commercialization. Scalable cell production platforms are needed to reliably deliver the cell quantities needed during the various stages of development and commercial supply. Human pluripotent stem cells (hPSCs) are a key source material for generating therapeutic cell types. We have developed a closed, automated and scalable stirred tank bioreactor platform, capable of sustaining high fold expansion of hPSCs. Such a platform could facilitate the in-process monitoring and integra

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McIntyre, Brendan A. S., Veronica Ramos-Mejia, Shravanti Rampalli, et al. "Gli3-mediated hedgehog inhibition in human pluripotent stem cells initiates and augments developmental programming of adult hematopoiesis." Blood 121, no. 9 (2013): 1543–52. http://dx.doi.org/10.1182/blood-2012-09-457747.

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Key Points Transient inhibition of hedgehog signaling augments hematopoiesis in hPSC-derived EBs. Hedgehog inhibition initiates an advancement in the developmental state of hematopoietic cells derived from hPSCs.

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Wadkin, L. E., S. Orozco-Fuentes, I. Neganova, M. Lako, N. G. Parker, and A. Shukurov. "A mathematical modelling framework for the regulation of intra-cellular OCT4 in human pluripotent stem cells." PLOS ONE 16, no. 8 (2021): e0254991. http://dx.doi.org/10.1371/journal.pone.0254991.

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Human pluripotent stem cells (hPSCs) have the potential to differentiate into all cell types, a property known as pluripotency. A deeper understanding of how pluripotency is regulated is required to assist in controlling pluripotency and differentiation trajectories experimentally. Mathematical modelling provides a non-invasive tool through which to explore, characterise and replicate the regulation of pluripotency and the consequences on cell fate. Here we use experimental data of the expression of the pluripotency transcription factor OCT4 in a growing hPSC colony to develop and evaluate mat

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Chang, Yolanda W., Arend W. Overeem, Celine M. Roelse, Xueying Fan, Christian Freund, and Susana M. Chuva de Sousa Lopes. "Tissue of Origin, but Not XCI State, Influences Germ Cell Differentiation from Human Pluripotent Stem Cells." Cells 10, no. 9 (2021): 2400. http://dx.doi.org/10.3390/cells10092400.

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Human pluripotent stem cells (hPSCs) are not only a promising tool to investigate differentiation to many cell types, including the germline, but are also a potential source of cells to use for regenerative medicine purposes in the future. However, current in vitro models to generate human primordial germ cell-like cells (hPGCLCs) have revealed high variability regarding differentiation efficiency depending on the hPSC lines used. Here, we investigated whether differences in X chromosome inactivation (XCI) in female hPSCs could contribute to the variability of hPGCLC differentiation efficiency

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Ran, Dan, Wei-Jong Shia, Miao-Chia Lo, et al. "RUNX1a Enhances Hematopoietic Lineage Commitment From Human Embryonic Stem Cells and Inducible Pluripotent Stem Cells." Blood 120, no. 21 (2012): 347. http://dx.doi.org/10.1182/blood.v120.21.347.347.

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Abstract Abstract 347 Both human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) are pluripotent stem cells (hPSCs) with potential to differentiate into all types of somatic cells. Patients suffering from blood disorders can be cured with hematopoietic cell transplantations (HCT). Technical advancements in hPSC production and handling have revolutionized their potential applications in regenerative medicine and provided enormous hope for patients who may need HCT. hiPSCs derived from autologous cells could provide unlimited leukocyte antigen matched blood cells on a pa

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Yuzuriha, Akinori, Sou Nakamura, Toshie Kusunoki, et al. "Environmental Cell-Matrix Adhesion Modulates Pluripotent Stem Cell Fate Toward Definitive Hemogenic Endothelium and Hematopoietic Progenitor Cells." Blood 132, Supplement 1 (2018): 3845. http://dx.doi.org/10.1182/blood-2018-99-114505.

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Abstract [Background] Human pluripotent stem cell (hPSC) technology enables regenerative transplantation therapy and establishment of in vitro disease models. hPSCs can be maintained to proliferate limitlessly and also differentiated to specific lineage cells, but hematopoietic cell differentiation efficiency varies among each hPSC lines. It has been reported the intrinsic expression level of transcription factors in hPSCs determine the commitment capacity toward hematopoietic cells (i.e. c-MYC [J Exp Med. 2010; 207: 2817-2830], IGF2 [Cell Stem Cell. 2016; 19: 341-354]). However, whether extra

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Barrault, Laetitia, Jacqueline Gide, Tingting Qing, et al. "Expression of miRNAs from the Imprinted DLK1/DIO3 Locus Signals the Osteogenic Potential of Human Pluripotent Stem Cells." Cells 8, no. 12 (2019): 1523. http://dx.doi.org/10.3390/cells8121523.

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Substantial variations in differentiation properties have been reported among human pluripotent cell lines (hPSC), which could affect their utility and clinical safety. We characterized the variable osteogenic capacity observed between different human pluripotent stem cell lines. By focusing on the miRNA expression profile, we demonstrated that the osteogenic differentiation propensity of human pluripotent stem cell lines could be associated with the methylation status and the expression of miRNAs from the imprinted DLK1/DIO3 locus. More specifically, quantitative analysis of the expression of

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Creamer, John Philip, Carissa Dege, Jolie T. K. Ho, Qihao Ren, Mark C. Valentine, and Christopher Michael Sturgeon. "Human Definitive Hematopoietic Specification from Pluripotent Stem Cells Is Regulated By Mesodermal Expression of CDX4." Blood 128, no. 22 (2016): 883. http://dx.doi.org/10.1182/blood.v128.22.883.883.

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Abstract The generation of hematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) is a major goal for regenerative medicine, as it will provide an unlimited source of these cells for transplantation, and a unique platform for the study of both normal and disease hematopoietic processes. To reproducibly achieve this goal in all hPSC lines, we must first fully understand hematopoietic ontogeny. Understanding hematopoietic development is complicated by the existence of at least two distinct programs during development that are difficult to distinguish: a transient "primitive" e

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Mianné, Joffrey, Chloé Bourguignon, Chloé Nguyen Van, et al. "Pipeline for the Generation and Characterization of Transgenic Human Pluripotent Stem Cells Using the CRISPR/Cas9 Technology." Cells 9, no. 5 (2020): 1312. http://dx.doi.org/10.3390/cells9051312.

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Recent advances in genome engineering based on the CRISPR/Cas9 technology have revolutionized our ability to manipulate genomic DNA. Its use in human pluripotent stem cells (hPSCs) has allowed a wide range of mutant cell lines to be obtained at an unprecedented rate. The combination of these two groundbreaking technologies has tremendous potential, from disease modeling to stem cell-based therapies. However, the generation, screening and molecular characterization of these cell lines remain a cumbersome and multi-step endeavor. Here, we propose a pipeline of strategies to efficiently generate,

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