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Cell Stem Cell Oct 2020Human pluripotent stem cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) provide unprecedented opportunities for cell therapies... (Review)
Review
Human pluripotent stem cells such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) provide unprecedented opportunities for cell therapies against intractable diseases and injuries. Both ESCs and iPSCs are already being used in clinical trials. However, we continue to encounter practical issues that limit their use, including their inherent properties of tumorigenicity, immunogenicity, and heterogeneity. Here, I review two decades of research aimed at overcoming these three difficulties.
Topics: Cell- and Tissue-Based Therapy; Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells; Stem Cell Transplantation
PubMed: 33007237
DOI: 10.1016/j.stem.2020.09.014 -
Cells Feb 2020The liver is a very complex organ that ensures numerous functions; it is thus susceptible to multiple types of damage and dysfunction. Since 1983, orthotopic liver... (Review)
Review
The liver is a very complex organ that ensures numerous functions; it is thus susceptible to multiple types of damage and dysfunction. Since 1983, orthotopic liver transplantation (OLT) has been considered the only medical solution available to patients when most of their liver function is lost. Unfortunately, the number of patients waiting for OLT is worryingly increasing, and extracorporeal liver support devices are not yet able to counteract the problem. In this review, the current and expected methodologies in liver regeneration are briefly analyzed. In particular, human pluripotent stem cells (hPSCs) as a source of hepatic cells for liver therapy and regeneration are discussed. Principles of hPSC differentiation into hepatocytes are explored, along with the current limitations that have led to the development of 3D culture systems and organoid production. Expected applications of these organoids are discussed with particular attention paid to bio artificial liver (BAL) devices and liver bio-fabrication.
Topics: Cell Differentiation; Cell- and Tissue-Based Therapy; Hepatocytes; Humans; Liver; Liver Diseases; Liver, Artificial; Organoids; Pluripotent Stem Cells; Regeneration
PubMed: 32059501
DOI: 10.3390/cells9020420 -
Philosophical Transactions of the Royal... Oct 2015Growing old is our destiny. However, the mature differentiated cells making up our body can be rejuvenated to an embryo-like fate called pluripotency which is an ability... (Review)
Review
Growing old is our destiny. However, the mature differentiated cells making up our body can be rejuvenated to an embryo-like fate called pluripotency which is an ability to differentiate into all cell types by enforced expression of defined transcription factors. The discovery of this induced pluripotent stem cell (iPSC) technology has opened up unprecedented opportunities in regenerative medicine, disease modelling and drug discovery. In this review, we introduce the applications and future perspectives of human iPSCs and we also show how iPSC technology has evolved along the way.
Topics: Animals; Cell Differentiation; Cell Transplantation; Cell- and Tissue-Based Therapy; Cellular Reprogramming; Drug Evaluation, Preclinical; Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Models, Biological; Regenerative Medicine
PubMed: 26416678
DOI: 10.1098/rstb.2014.0367 -
Circulation Research Apr 2020Maturation is the last phase of heart development that prepares the organ for strong, efficient, and persistent pumping throughout the mammal's lifespan. This process is... (Review)
Review
Maturation is the last phase of heart development that prepares the organ for strong, efficient, and persistent pumping throughout the mammal's lifespan. This process is characterized by structural, gene expression, metabolic, and functional specializations in cardiomyocytes as the heart transits from fetal to adult states. Cardiomyocyte maturation gained increased attention recently due to the maturation defects in pluripotent stem cell-derived cardiomyocyte, its antagonistic effect on myocardial regeneration, and its potential contribution to cardiac disease. Here, we review the major hallmarks of ventricular cardiomyocyte maturation and summarize key regulatory mechanisms that promote and coordinate these cellular events. With advances in the technical platforms used for cardiomyocyte maturation research, we expect significant progress in the future that will deepen our understanding of this process and lead to better maturation of pluripotent stem cell-derived cardiomyocyte and novel therapeutic strategies for heart disease.
Topics: Animals; Cell Differentiation; Heart Diseases; Humans; Myocytes, Cardiac; Pluripotent Stem Cells
PubMed: 32271675
DOI: 10.1161/CIRCRESAHA.119.315862 -
Stem Cell Reports Aug 2023
Topics: Pluripotent Stem Cells; Induced Pluripotent Stem Cells; Cell Differentiation; Cell- and Tissue-Based Therapy; Stem Cell Transplantation
PubMed: 37557071
DOI: 10.1016/j.stemcr.2023.06.010 -
Stem Cell Research & Therapy Dec 2014Heart disease remains the number one cause of death in developed countries. Loss of cardiomyocytes (CMs) due to aging or pathophysiological conditions (for example,...
Heart disease remains the number one cause of death in developed countries. Loss of cardiomyocytes (CMs) due to aging or pathophysiological conditions (for example, myocardial infarction) is generally considered irreversible, and can lead to lethal conditions from cardiac arrhythmias to heart failure. Human pluripotent stem cells (PSCs), including embryonic stem cells and induced pluripotent stem cells (iPSCs), can self-renew while maintaining their pluripotency to differentiate into all cell types, including CMs. As such, PSCs represent an unprecedented unlimited ex vivo cell source. In the present thematic series, we have solicited seven review articles to discuss the current state-of-the-art PSC-based approaches for such applications as disease modeling, discovery of novel drugs and therapeutics, cardiotoxicity screening and cell-based myocardial repair, as well as the associated hurdles and potential solutions.
Topics: Animals; Cardiovascular Physiological Phenomena; Humans; Pluripotent Stem Cells; Regeneration
PubMed: 25689157
DOI: 10.1186/scrt531 -
ELife Mar 2015Recent breakthroughs in 3-dimensional (3D) organoid cultures for many organ systems have led to new physiologically complex in vitro models to study human development...
Recent breakthroughs in 3-dimensional (3D) organoid cultures for many organ systems have led to new physiologically complex in vitro models to study human development and disease. Here, we report the step-wise differentiation of human pluripotent stem cells (hPSCs) (embryonic and induced) into lung organoids. By manipulating developmental signaling pathways hPSCs generate ventral-anterior foregut spheroids, which are then expanded into human lung organoids (HLOs). HLOs consist of epithelial and mesenchymal compartments of the lung, organized with structural features similar to the native lung. HLOs possess upper airway-like epithelium with basal cells and immature ciliated cells surrounded by smooth muscle and myofibroblasts as well as an alveolar-like domain with appropriate cell types. Using RNA-sequencing, we show that HLOs are remarkably similar to human fetal lung based on global transcriptional profiles, suggesting that HLOs are an excellent model to study human lung development, maturation and disease.
Topics: Cell Culture Techniques; Cell Differentiation; Cell Line; Cells, Cultured; Embryonic Stem Cells; Endoderm; Gene Expression Profiling; Humans; Induced Pluripotent Stem Cells; Lung; Microscopy, Confocal; Microscopy, Electron, Transmission; Organogenesis; Organoids; Pluripotent Stem Cells; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Spheroids, Cellular; Tissue Engineering
PubMed: 25803487
DOI: 10.7554/eLife.05098 -
Regenerative Medicine Oct 2018Use of clinical-grade human induced pluripotent stem cell (iPSC) lines as a starting material for the generation of cellular therapeutics requires demonstration of...
Use of clinical-grade human induced pluripotent stem cell (iPSC) lines as a starting material for the generation of cellular therapeutics requires demonstration of comparability of lines derived from different individuals and in different facilities. This requires agreement on the critical quality attributes of such lines and the assays that should be used. Working from established recommendations and guidance from the International Stem Cell Banking Initiative for human embryonic stem cell banking, and concentrating on those issues more relevant to iPSCs, a series of consensus workshops has made initial recommendations on the minimum dataset required to consider an iPSC line of clinical grade, which are outlined in this report. Continued evolution of this field will likely lead to revision of these guidelines on a regular basis.
Topics: Cell Line; Cell- and Tissue-Based Therapy; Humans; Induced Pluripotent Stem Cells; Practice Guidelines as Topic; Quality Control
PubMed: 30205750
DOI: 10.2217/rme-2018-0095 -
Cell Stem Cell Dec 2017Organogenesis generates higher-order structures containing functional subunits, connective components, and progenitor niches. Despite recent advances in organoid-based...
Organogenesis generates higher-order structures containing functional subunits, connective components, and progenitor niches. Despite recent advances in organoid-based modeling of tissue development, recapitulating these complex configurations from pluripotent stem cells (PSCs) has remained challenging. In this study, we report assembly of kidney organoids that recapitulate embryonic branching morphogenesis. By studying the distinct origins and developmental processes of the ureteric bud, which contains epithelial kidney progenitors that undergo branching morphogenesis and thereby plays a central role in orchestrating organ geometry, and neighboring mesenchymal nephron progenitors, we established a protocol for differential induction of each lineage from mouse and human PSCs. Importantly, reassembled organoids developed the inherent architectures of the embryonic kidney, including the peripheral progenitor niche and internally differentiated nephrons that were interconnected by a ramified ureteric epithelium. This selective induction and reassembly strategy will be a powerful approach to recapitulate organotypic architecture in PSC-derived organoids.
Topics: Animals; Cells, Cultured; Humans; Kidney; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Organogenesis; Pluripotent Stem Cells
PubMed: 29129523
DOI: 10.1016/j.stem.2017.10.011 -
Cell Apr 2021Interspecies chimera formation with human pluripotent stem cells (hPSCs) represents a necessary alternative to evaluate hPSC pluripotency in vivo and might constitute a...
Interspecies chimera formation with human pluripotent stem cells (hPSCs) represents a necessary alternative to evaluate hPSC pluripotency in vivo and might constitute a promising strategy for various regenerative medicine applications, including the generation of organs and tissues for transplantation. Studies using mouse and pig embryos suggest that hPSCs do not robustly contribute to chimera formation in species evolutionarily distant to humans. We studied the chimeric competency of human extended pluripotent stem cells (hEPSCs) in cynomolgus monkey (Macaca fascicularis) embryos cultured ex vivo. We demonstrate that hEPSCs survived, proliferated, and generated several peri- and early post-implantation cell lineages inside monkey embryos. We also uncovered signaling events underlying interspecific crosstalk that may help shape the unique developmental trajectories of human and monkey cells within chimeric embryos. These results may help to better understand early human development and primate evolution and develop strategies to improve human chimerism in evolutionarily distant species.
Topics: Animals; Blastocyst; Cell Differentiation; Cell Lineage; Cells, Cultured; Chimerism; Embryo, Mammalian; Female; Humans; Macaca fascicularis; Pluripotent Stem Cells; RNA-Seq; Single-Cell Analysis; Transcriptome
PubMed: 33861963
DOI: 10.1016/j.cell.2021.03.020