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Journal articles on the topic 'HPSC'

Author: Grafiati

Published: 4 June 2021

Last updated: 21 December 2024

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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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Vojnits, Kinga, Mio Nakanishi, Deanna Porras, et al. "Developing CRISPR/Cas9-Mediated Fluorescent Reporter Human Pluripotent Stem-Cell Lines for High-Content Screening." Molecules 27, no. 8 (2022): 2434. http://dx.doi.org/10.3390/molecules27082434.

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Application of the CRISPR/Cas9 system to knock in fluorescent proteins to endogenous genes of interest in human pluripotent stem cells (hPSCs) has the potential to facilitate hPSC-based disease modeling, drug screening, and optimization of transplantation therapy. To evaluate the capability of fluorescent reporter hPSC lines for high-content screening approaches, we targeted EGFP to the endogenous OCT4 locus. Resulting hPSC–OCT4–EGFP lines generated expressed EGFP coincident with pluripotency markers and could be adapted to multi-well formats for high-content screening (HCS) campaigns. However

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Hai, Nan, Dong Shin, Huanjing Bi, Kaiming Ye, and Sha Jin. "Mechanistic Analysis of Physicochemical Cues in Promoting Human Pluripotent Stem Cell Self-Renewal and Metabolism." International Journal of Molecular Sciences 19, no. 11 (2018): 3459. http://dx.doi.org/10.3390/ijms19113459.

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We have previously reported that a porous membrane of polyethylene terephthalate (PET) enables significant augmentation of human pluripotent stem cell (hPSC) proliferation and differentiation. The interaction between hPSCs and the PET surface induces β-catenin-mediated wingless/integrated (Wnt) signaling, leading to upregulation of the expression of adhesion molecules in hPSCs. In this study, we sought to unveil mechanisms underlying the role of the PET membrane in hPSC self-renewal and metabolism. We discovered that physicochemical cues of the PET membrane considerably alter hPSC metabolism 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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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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Armstrong, Alison J., Hal Hansen, and Roger Gauthier. "Development of a Model for Evaluating High Performance Sport Centers in Canada." Journal of Sport Management 5, no. 2 (1991): 153–76. http://dx.doi.org/10.1123/jsm.5.2.153.

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A theory based model was developed for the evaluation of high performance sport centers (HPSCs) in Canada. The model was developed according to de Groot’s (1969) four-phase interpretative-theoretical methodology. The phases of exploration, analysis, classification, and explanation guided the collection of current program evaluation literature and information on the nature of the HPSC program and its past evaluation practices. Appropriate evaluation models from the literature were assessed with respect to the HPSC program’s nature, and a single theoretical-integrative model was developed with c

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Yamada, Daisuke, Tomoka Takao, Masahiro Nakamura, Toki Kitano, Eiji Nakata, and Takeshi Takarada. "Identification of Surface Antigens That Define Human Pluripotent Stem Cell-Derived PRRX1+Limb-Bud-like Mesenchymal Cells." International Journal of Molecular Sciences 23, no. 5 (2022): 2661. http://dx.doi.org/10.3390/ijms23052661.

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Stem cell-based therapies and experimental methods rely on efficient induction of human pluripotent stem cells (hPSCs). During limb development, the lateral plate mesoderm (LPM) produces limb-bud mesenchymal (LBM) cells that differentiate into osteochondroprogenitor cells and form cartilage tissues in the appendicular skeleton. Previously, we generated PRRX1-tdTomato reporter hPSCs to establish the protocol for inducing the hPSC-derived PRRX1+ LBM-like cells. However, surface antigens that assess the induction efficiency of hPSC-derived PRRX1+ LBM-like cells from LPM have not been identified.

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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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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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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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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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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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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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Park, Seo-Yeon, and Yong Kyun Kim. "Strategies for vascularization in kidney organoids." Organoid 1 (August 15, 2021): e14. http://dx.doi.org/10.51335/organoid.2021.1.e14.

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The establishment of protocols for differentiating kidney organoids from human pluripotent stem cells (hPSCs) has potential for the application of kidney organoids in regenerative medicine. However, the primary obstacle to the regenerative application of hPSC-derived kidney organoids is precise vascularization due to the lack of vasculature in hPSC-derived kidney organoids. In this article, we review the recent methodologies for developing vasculature of kidney organoids to overcome this limitation of kidney organoids, together with a discussion of their clinical applications.

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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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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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Schwach, Verena, Carla Cofiño-Fabres, Simone A. ten Den та Robert Passier. "Improved Atrial Differentiation of Human Pluripotent Stem Cells by Activation of Retinoic Acid Receptor Alpha (RARα)". Journal of Personalized Medicine 12, № 4 (2022): 628. http://dx.doi.org/10.3390/jpm12040628.

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Human pluripotent stem cell (hPSC)-derived cardiomyocytes have proven valuable for modeling disease and as a drug screening platform. Here, we depict an optimized protocol for the directed differentiation of hPSCs toward cardiomyocytes with an atrial identity by modulating the retinoic acid signaling cascade in spin embryoid bodies. The crucial steps of the protocol, including hPSC maintenance, embryoid body (EB) differentiation, the induction of cardiac mesoderm, direction toward the atrial phenotype, as well as molecular and functional characterization of the cardiomyocytes, are described. A

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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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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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Hayes, Kevin, Yun-Kyo Kim, and Martin F. Pera. "A Case for Revisiting Nodal Signaling in Human Pluripotent Stem Cells." Stem Cells 39, no. 9 (2021): 1137–44. http://dx.doi.org/10.1002/stem.3383.

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Abstract Nodal is a transforming growth factor-β (TGF-β) superfamily member that plays a number of critical roles in mammalian embryonic development. Nodal is essential for the support of the peri-implantation epiblast in the mouse embryo and subsequently acts to specify mesendodermal fate at the time of gastrulation and, later, left-right asymmetry. Maintenance of human pluripotent stem cells (hPSCs) in vitro is dependent on Nodal signaling. Because it has proven difficult to prepare a biologically active form of recombinant Nodal protein, Activin or TGFB1 are widely used as surrogates for NO

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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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Chang, Xuyao, Mingxia Gu, and Jason Tchieu. "Harnessing the Power of Stem Cell Models to Study Shared Genetic Variants in Congenital Heart Diseases and Neurodevelopmental Disorders." Cells 11, no. 3 (2022): 460. http://dx.doi.org/10.3390/cells11030460.

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Advances in human pluripotent stem cell (hPSC) technology allow one to deconstruct the human body into specific disease-relevant cell types or create functional units representing various organs. hPSC-based models present a unique opportunity for the study of co-occurring disorders where “cause and effect” can be addressed. Poor neurodevelopmental outcomes have been reported in children with congenital heart diseases (CHD). Intuitively, abnormal cardiac function or surgical intervention may stunt the developing brain, leading to neurodevelopmental disorders (NDD). However, recent work has unco

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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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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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Porras, Deanna P., Jennifer C. Reid, Borko Tanasijevic, Diana Golubeva, Allison L. Boyd, and Mickie Bhatia. "Challenges in Cell Fate Acquisition to Scid-Repopulating Activity from Hemogenic Endothelium of hiPSCs Derived from AML Patients Using Forced Transcription Factor Expression." Cells 11, no. 12 (2022): 1915. http://dx.doi.org/10.3390/cells11121915.

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The generation of human hematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) represents a major goal in regenerative medicine and is believed would follow principles of early development. HSCs arise from a type of endothelial cell called a “hemogenic endothelium” (HE), and human HSCs are experimentally detected by transplantation into SCID or other immune-deficient mouse recipients, termed SCID-Repopulating Cells (SRC). Recently, SRCs were detected by forced expression of seven transcription factors (TF) (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1, and SPI1) in hPSC-derived HE

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Chen, Yu-Fan, Yi-Shuan J. Li, Chih-Hung Chou, et al. "Control of matrix stiffness promotes endodermal lineage specification by regulating SMAD2/3 via lncRNA LINC00458." Science Advances 6, no. 6 (2020): eaay0264. http://dx.doi.org/10.1126/sciadv.aay0264.

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During endoderm formation, cell identity and tissue morphogenesis are tightly controlled by cell-intrinsic and cell-extrinsic factors such as biochemical and physical inputs. While the effects of biochemical factors are well studied, the physical cues that regulate cell division and differentiation are poorly understood. RNA sequencing analysis demonstrated increases of endoderm-specific gene expression in hPSCs cultured on soft substrate (Young’s modulus, 3 ± 0.45 kPa) in comparison with hard substrate (Young’s modulus, 165 ± 6.39 kPa). Further analyses revealed that multiple long noncoding R

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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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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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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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Souidi, Monia, Yvonne Sleiman, Ivana Acimovic, et al. "Oxygen Is an Ambivalent Factor for the Differentiation of Human Pluripotent Stem Cells in Cardiac 2D Monolayer and 3D Cardiac Spheroids." International Journal of Molecular Sciences 22, no. 2 (2021): 662. http://dx.doi.org/10.3390/ijms22020662.

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Numerous protocols of cardiac differentiation have been established by essentially focusing on specific growth factors on human pluripotent stem cell (hPSC) differentiation efficiency. However, the optimal environmental factors to obtain cardiac myocytes in network are still unclear. The mesoderm germ layer differentiation is known to be enhanced by low oxygen exposure. Here, we hypothesized that low oxygen exposure enhances the molecular and functional maturity of the cardiomyocytes. We aimed at comparing the molecular and functional consequences of low (5% O2 or LOE) and high oxygen exposure

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Souidi, Monia, Yvonne Sleiman, Ivana Acimovic, et al. "Oxygen Is an Ambivalent Factor for the Differentiation of Human Pluripotent Stem Cells in Cardiac 2D Monolayer and 3D Cardiac Spheroids." International Journal of Molecular Sciences 22, no. 2 (2021): 662. http://dx.doi.org/10.3390/ijms22020662.

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Numerous protocols of cardiac differentiation have been established by essentially focusing on specific growth factors on human pluripotent stem cell (hPSC) differentiation efficiency. However, the optimal environmental factors to obtain cardiac myocytes in network are still unclear. The mesoderm germ layer differentiation is known to be enhanced by low oxygen exposure. Here, we hypothesized that low oxygen exposure enhances the molecular and functional maturity of the cardiomyocytes. We aimed at comparing the molecular and functional consequences of low (5% O2 or LOE) and high oxygen exposure

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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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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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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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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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Oh, Jisun, Oh-Bin Kwon, Sang-Wook Park, et al. "Advancing Cardiovascular Drug Screening Using Human Pluripotent Stem Cell-Derived Cardiomyocytes." International Journal of Molecular Sciences 25, no. 14 (2024): 7971. http://dx.doi.org/10.3390/ijms25147971.

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Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have emerged as a promising tool for studying cardiac physiology and drug responses. However, their use is largely limited by an immature phenotype and lack of high-throughput analytical methodology. In this study, we developed a high-throughput testing platform utilizing hPSC-CMs to assess the cardiotoxicity and effectiveness of drugs. Following an optimized differentiation and maturation protocol, hPSC-CMs exhibited mature CM morphology, phenotype, and functionality, making them suitable for drug testing applications. We monitored

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Barra, Jessie, Rob Robino, Roberto Castro-Gutierrez, Leonardo Ferreira, and Holger Russ. "Combinatorial genome engineering strategy for CAR-Treg antigen-specific immune protection of stem cell-derived cells." Journal of Immunology 212, no. 1_Supplement (2024): 1538_4544. http://dx.doi.org/10.4049/jimmunol.212.supp.1538.4544.

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Abstract Improved methods for generating human pluripotent stem cell (hPSC)-derived cells and tissues have rapidly expanded the field of regenerative medicine. Yet, in most cases, hPSC-derived cells need to be protected, ideally in a localized manner, from an antagonistic host immune response. Chimeric antigen receptor (CAR) technology can confer new antigen specificities to effector T cells and, more recently, regulatory T cells (Tregs), potent immunosuppressive cells. However, one challenge in CAR design is identifying a target molecule uniquely expressed by the cells of interest to prevent

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Qian, Shiguang, Hong-Shiue Chou, Ronald Charles, John Fung, and Lina Lu. "Induction of cell transplant tolerance: a roadmap from bench to bedside (P2220)." Journal of Immunology 190, no. 1_Supplement (2013): 69.48. http://dx.doi.org/10.4049/jimmunol.190.supp.69.48.

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Abstract Organ transplants have worked for decades, but outcomes of cell transplants remain disappointing. Enlightened by mouse liver allografts being spontaneously accepted, but hepatocyte transplants acutely rejected (suggesting lack of non-parenchymal cell protection), we identified strong regulatory activity of hepatic stellate cells (HpSC). Islet allografts (300) mixed with HpSC (3x105) achieved long survival without immunosuppression, associated with apoptosis of CD8 T cells, enhancement of Tregs, which depends on IFNγ/B7-H1 pathway. However, co-transplanted HpSC have to be syngeneic to

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Weis, Victoria G., Anna C. Deal, Gehad Mekkey, et al. "Human placental-derived stem cell therapy ameliorates experimental necrotizing enterocolitis." American Journal of Physiology-Gastrointestinal and Liver Physiology 320, no. 4 (2021): G658—G674. http://dx.doi.org/10.1152/ajpgi.00369.2020.

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These studies demonstrate a human placental-derived stem cell (hPSC) therapeutic strategy for necrotizing enterocolitis (NEC). In an experimental model of NEC, hPSC administration improved macroscopic intestinal health, ameliorated epithelial morphology, and supported the intestinal stem cell niche. Our data suggest that hPSC are a potential therapeutic approach to attenuate established intestinal NEC damage. Further, we show hPSC are a novel research tool that can be utilized to elucidate critical neonatal repair mechanisms to overcome NEC.

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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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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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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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Long, Hong-Yan, Zu-Ping Qian, Qin Lan, et al. "Human pluripotent stem cell-derived kidney organoids: Current progress and challenges." World Journal of Stem Cells 16, no. 2 (2024): 114–25. http://dx.doi.org/10.4252/wjsc.v16.i2.114.

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Human pluripotent stem cell (hPSC)-derived kidney organoids share similarities with the fetal kidney. However, the current hPSC-derived kidney organoids have some limitations, including the inability to perform nephrogenesis and lack of a corticomedullary definition, uniform vascular system, and coordinated exit pathway for urinary filtrate. Therefore, further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development, regeneration, disease modeling, and drug screening. In this review, we discussed recent advan

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Cotovio, João P., and Tiago G. Fernandes. "Production of Human Pluripotent Stem Cell-Derived Hepatic Cell Lineages and Liver Organoids: Current Status and Potential Applications." Bioengineering 7, no. 2 (2020): 36. http://dx.doi.org/10.3390/bioengineering7020036.

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Liver disease is one of the leading causes of death worldwide, leading to the death of approximately 2 million people per year. Current therapies include orthotopic liver transplantation, however, donor organ shortage remains a great challenge. In addition, the development of novel therapeutics has been limited due to the lack of in vitro models that mimic in vivo liver physiology. Accordingly, hepatic cell lineages derived from human pluripotent stem cells (hPSCs) represent a promising cell source for liver cell therapy, disease modelling, and drug discovery. Moreover, the development of new

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Ashok, Preeti, and Emmanuel S. Tzanakakis. "Proteomic Analysis of Exosomes during Cardiogenic Differentiation of Human Pluripotent Stem Cells." Cells 10, no. 10 (2021): 2622. http://dx.doi.org/10.3390/cells10102622.

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Efforts to direct the specification of human pluripotent stem cells (hPSCs) to therapeutically important somatic cell types have focused on identifying proper combinations of soluble cues. Yet, whether exosomes, which mediate intercellular communication, play a role in the differentiation remains unexplored. We took a first step toward addressing this question by subjecting hPSCs to stage-wise specification toward cardiomyocytes (CMs) in scalable stirred-suspension cultures and collecting exosomes. Samples underwent liquid chromatography (LC)/mass spectrometry (MS) and subsequent proteomic ana

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Pelkonen, Anssi, Cristiana Pistono, Pamela Klecki, et al. "Functional Characterization of Human Pluripotent Stem Cell-Derived Models of the Brain with Microelectrode Arrays." Cells 11, no. 1 (2021): 106. http://dx.doi.org/10.3390/cells11010106.

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Human pluripotent stem cell (hPSC)-derived neuron cultures have emerged as models of electrical activity in the human brain. Microelectrode arrays (MEAs) measure changes in the extracellular electric potential of cell cultures or tissues and enable the recording of neuronal network activity. MEAs have been applied to both human subjects and hPSC-derived brain models. Here, we review the literature on the functional characterization of hPSC-derived two- and three-dimensional brain models with MEAs and examine their network function in physiological and pathological contexts. We also summarize M

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Bai, Hao, Yin-Liang Xie, Yong-Xing Gao, Tao Cheng, and Zack Z. Wang. "The Balance of Positive and Negative Effects of TGF-Beta Signaling Regulates the Hemangioblast Development in Human Pluripotent Stem Cells." Blood 120, no. 21 (2012): 1220. http://dx.doi.org/10.1182/blood.v120.21.1220.1220.

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Abstract Abstract 1220 Derived from mesoderm precursors, hemangioblasts are bipotential common progenitors of hematopoietic cells and endothelial cells. The regulatory events controlling human hemangioblast development are largely unknown. Our previous study demonstrated that CD34 progenitors from human embryonic stem cells (hESCs) contain a population of cells that give rise to hematopoietic cells and endothelial cells. In this study, we established a serum-free and feeder-free system to investigate the signals that direct differentiation of human pluripotent stem cells (hPSCs), including hES

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Ribeiro, Alexandre J. S., Yen-Sin Ang, Ji-Dong Fu, et al. "Contractility of single cardiomyocytes differentiated from pluripotent stem cells depends on physiological shape and substrate stiffness." Proceedings of the National Academy of Sciences 112, no. 41 (2015): 12705–10. http://dx.doi.org/10.1073/pnas.1508073112.

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Single cardiomyocytes contain myofibrils that harbor the sarcomere-based contractile machinery of the myocardium. Cardiomyocytes differentiated from human pluripotent stem cells (hPSC-CMs) have potential as an in vitro model of heart activity. However, their fetal-like misalignment of myofibrils limits their usefulness for modeling contractile activity. We analyzed the effects of cell shape and substrate stiffness on the shortening and movement of labeled sarcomeres and the translation of sarcomere activity to mechanical output (contractility) in live engineered hPSC-CMs. Single hPSC-CMs were

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Al-attar, Rasha, Joseph Jargstorf, Rocco Romagnuolo, et al. "Casein Kinase 1 Phosphomimetic Mutations Negatively Impact Connexin-43 Gap Junctions in Human Pluripotent Stem Cell-Derived Cardiomyocytes." Biomolecules 14, no. 1 (2024): 61. http://dx.doi.org/10.3390/biom14010061.

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The transplantation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) has shown promise in preclinical models of myocardial infarction, but graft myocardium exhibits incomplete host–graft electromechanical integration and a propensity for pro-arrhythmic behavior. Perhaps contributing to this situation, hPSC-CM grafts show low expression of connexin 43 (Cx43), the major gap junction (GJ) protein, in ventricular myocardia. We hypothesized that Cx43 expression and function could be rescued by engineering Cx43 in hPSC-CMs with a series of phosphatase-resistant mutations at three cas

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Esfahani, Sajedeh Nasr, Yi Zheng, Auriana Arabpour, et al. "Derivation of human primordial germ cell-like cells in an embryonic-like culture." Nature Communications 15, no. 1 (2024). http://dx.doi.org/10.1038/s41467-023-43871-2.

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AbstractPrimordial germ cells (PGCs) are the embryonic precursors of sperm and eggs. They transmit genetic and epigenetic information across generations. Given the prominent role of germline defects in diseases such as infertility, detailed understanding of human PGC (hPGC) development has important implications in reproductive medicine and studying human evolution. Yet, hPGC specification remains an elusive process. Here, we report the induction of hPGC-like cells (hPGCLCs) in a bioengineered human pluripotent stem cell (hPSC) culture that mimics peri-implantation human development. In this c

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