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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 -
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 -
Progress in Neurobiology Sep 2018Parkinson's disease (PD) is one of the most common neurodegenerative disorders, which affects about 0.3% of the general population. As the population in the developed... (Review)
Review
Parkinson's disease (PD) is one of the most common neurodegenerative disorders, which affects about 0.3% of the general population. As the population in the developed world ages, this creates an escalating burden on society both in economic terms and in quality of life for these patients and for the families that support them. Although currently available pharmacological or surgical treatments may significantly improve the quality of life of many patients with PD, these are symptomatic treatments that do not slow or stop the progressive course of the disease. Because motor impairments in PD largely result from loss of midbrain dopamine neurons in the substantia nigra pars compacta, PD has long been considered to be one of the most promising target diseases for cell-based therapy. Indeed, numerous clinical and preclinical studies using fetal cell transplantation have provided proof of concept that cell replacement therapy may be a viable therapeutic approach for PD. However, the use of human fetal cells as a standardized therapeutic regimen has been fraught with fundamental ethical, practical, and clinical issues, prompting scientists to explore alternative cell sources. Based on groundbreaking establishments of human embryonic stem cells and induced pluripotent stem cells, these human pluripotent stem cells have been the subject of extensive research, leading to tremendous advancement in our understanding of these novel classes of stem cells and promising great potential for regenerative medicine. In this review, we discuss the prospects and challenges of human pluripotent stem cell-based cell therapy for PD.
Topics: Humans; Parkinson Disease; Pluripotent Stem Cells; Stem Cell Transplantation
PubMed: 29653250
DOI: 10.1016/j.pneurobio.2018.04.005 -
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 -
Arteriosclerosis, Thrombosis, and... Nov 2017The emergence of induced pluripotent stem cell (iPSC) technology paves the way to generate large numbers of patient-specific endothelial cells (ECs) that can be... (Review)
Review
The emergence of induced pluripotent stem cell (iPSC) technology paves the way to generate large numbers of patient-specific endothelial cells (ECs) that can be potentially delivered for regenerative medicine in patients with cardiovascular disease. In the last decade, numerous protocols that differentiate EC from iPSC have been developed by many groups. In this review, we will discuss several common strategies that have been optimized for human iPSC-EC differentiation and subsequent studies that have evaluated the potential of human iPSC-EC as a cell therapy or as a tool in disease modeling. In addition, we will emphasize the importance of using in vivo vessel-forming ability and in vitro clonogenic colony-forming potential as a gold standard with which to evaluate the quality of human iPSC-EC derived from various protocols.
Topics: Animals; Cardiovascular Diseases; Cell Differentiation; Cell Line; Disease Models, Animal; Endothelial Cells; Gene Expression Regulation, Developmental; Humans; Induced Pluripotent Stem Cells; Phenotype; Regenerative Medicine
PubMed: 29025705
DOI: 10.1161/ATVBAHA.117.309962 -
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 -
Cells Jun 2023Red blood cell (RBC) transfusion is a lifesaving medical procedure that can treat patients with anemia and hemoglobin disorders. However, the shortage of blood supply... (Review)
Review
Red blood cell (RBC) transfusion is a lifesaving medical procedure that can treat patients with anemia and hemoglobin disorders. However, the shortage of blood supply and risks of transfusion-transmitted infection and immune incompatibility present a challenge for transfusion. The in vitro generation of RBCs or erythrocytes holds great promise for transfusion medicine and novel cell-based therapies. While hematopoietic stem cells and progenitors derived from peripheral blood, cord blood, and bone marrow can give rise to erythrocytes, the use of human pluripotent stem cells (hPSCs) has also provided an important opportunity to obtain erythrocytes. These hPSCs include both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). As hESCs carry ethical and political controversies, hiPSCs can be a more universal source for RBC generation. In this review, we first discuss the key concepts and mechanisms of erythropoiesis. Thereafter, we summarize different methodologies to differentiate hPSCs into erythrocytes with an emphasis on the key features of human definitive erythroid lineage cells. Finally, we address the current limitations and future directions of clinical applications using hiPSC-derived erythrocytes.
Topics: Humans; Induced Pluripotent Stem Cells; Cell Differentiation; Erythrocytes; Pluripotent Stem Cells; Hematopoietic Stem Cells
PubMed: 37296674
DOI: 10.3390/cells12111554 -
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