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Cell Stem Cell Apr 2018The liver, lung, pancreas, and digestive tract all originate from the endoderm germ layer, and these vital organs are subject to many life-threatening diseases affecting... (Review)
Review
The liver, lung, pancreas, and digestive tract all originate from the endoderm germ layer, and these vital organs are subject to many life-threatening diseases affecting millions of patients. However, primary cells from endodermal organs are often difficult to grow in vitro. Human pluripotent stem cells thus hold great promise for generating endoderm cells and their derivatives as tools for the development of new therapeutics against a variety of global healthcare challenges. Here we describe recent advances in methods for generating endodermal cell types from human pluripotent stem cells and their use for disease modeling and cell-based therapy.
Topics: Endoderm; Humans; Models, Biological; Pluripotent Stem Cells
PubMed: 29625066
DOI: 10.1016/j.stem.2018.03.016 -
The Thoracic and Cardiovascular Surgeon Jan 2018For more than 20 years, tremendous efforts have been made to develop cell-based therapies for treatment of heart failure. However, the results of clinical trials using... (Review)
Review
For more than 20 years, tremendous efforts have been made to develop cell-based therapies for treatment of heart failure. However, the results of clinical trials using somatic, nonpluripotent stem or progenitor cells have been largely disappointing in both cardiology and cardiac surgery scenarios. Surgical groups were among the pioneers of experimental and clinical myocyte transplantation ("cellular cardiomyoplasty"), but little translational progress was made prior to the development of cellular reprogramming for creation of induced pluripotent stem cells (iPSC). Ever since, protocols have been developed which allow for the derivation of large numbers of autologous cardiomyocytes (CMs) from patient-specific iPSC, moving translational research closer toward clinical pilot trials. However, compared with somatic cell therapy, the technology required for safe and efficacious pluripotent stem cell (PSC)-based therapies is extremely complex and requires tremendous resources and close interactions between basic scientists and clinicians. This review summarizes PSC sources, strategies to derive CMs, current cardiac tissue engineering approaches, concerns regarding immunogenicity and cellular maturity, and highlights the contributions made by surgical groups.
Topics: Animals; Cardiovascular Diseases; Cell Lineage; Cellular Reprogramming; Cellular Reprogramming Techniques; Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Myocardium; Myocytes, Cardiac; Phenotype; Pluripotent Stem Cells; Recovery of Function; Regeneration; Regenerative Medicine; Signal Transduction; Treatment Outcome
PubMed: 29216651
DOI: 10.1055/s-0037-1608761 -
Current Cardiology Reports Jun 2020This review summarizes the important role that metabolism plays in driving maturation of human pluripotent stem cell-derived cardiomyocytes. (Review)
Review
PURPOSE OF REVIEW
This review summarizes the important role that metabolism plays in driving maturation of human pluripotent stem cell-derived cardiomyocytes.
RECENT FINDINGS
Human pluripotent stem cell-derived cardiomyocytes provide a model system for human cardiac biology. However, these models have been unable to fully recapitulate the maturity observed in the adult heart. By simulating the glucose to fatty acid transition observed in neonatal mammals, human pluripotent stem cell-derived cardiomyocytes undergo structural and functional maturation also accompanied by transcriptional changes and cell cycle arrest. The role of metabolism in energy production, signaling, and epigenetic modifications illustrates that metabolism and cellular phenotype are intimately linked. Further understanding of key metabolic factors driving cardiac maturation will facilitate the generation of more mature human pluripotent stem cell-derived cardiomyocyte models. This will increase our understanding of cardiac biology and potentially lead to novel therapeutics to enhance heart function.
Topics: Adult; Animals; Cell Differentiation; Humans; Induced Pluripotent Stem Cells; Myocytes, Cardiac; Pluripotent Stem Cells; Signal Transduction
PubMed: 32594263
DOI: 10.1007/s11886-020-01303-3 -
Current Cardiology Reports May 2022Exciting pre-clinical data presents pluripotent stem cell-derived cardiomyocytes (PSC-CM) as a novel therapeutic prospect following myocardial infarction, and worldwide... (Review)
Review
PURPOSE OF REVIEW
Exciting pre-clinical data presents pluripotent stem cell-derived cardiomyocytes (PSC-CM) as a novel therapeutic prospect following myocardial infarction, and worldwide clinical trials are imminent. However, despite notable advances, several challenges remain. Here, we review PSC-CM pre-clinical studies, identifying key translational hurdles. We further discuss cell production and characterization strategies, identifying markers that may help generate cells which overcome these barriers.
RECENT FINDINGS
PSC-CMs can robustly repopulate infarcted myocardium with functional, force generating cardiomyocytes. However, current differentiation protocols produce immature and heterogenous cardiomyocytes, creating related issues such as arrhythmogenicity, immunogenicity and poor engraftment. Recent efforts have enhanced our understanding of cardiovascular developmental biology. This knowledge may help implement novel differentiation or gene editing strategies that could overcome these limitations. PSC-CMs are an exciting therapeutic prospect. Despite substantial recent advances, limitations of the technology remain. However, with our continued and increasing biological understanding, these issues are addressable, with several worldwide clinical trials anticipated in the coming years.
Topics: Cell Differentiation; Cell- and Tissue-Based Therapy; Humans; Induced Pluripotent Stem Cells; Myocardium; Myocytes, Cardiac; Pluripotent Stem Cells
PubMed: 35275365
DOI: 10.1007/s11886-022-01666-9 -
Experimental Biology and Medicine... Apr 2021The last decade has seen many exciting technological breakthroughs that greatly expanded the toolboxes for biological and biomedical research, yet few have had more... (Review)
Review
The last decade has seen many exciting technological breakthroughs that greatly expanded the toolboxes for biological and biomedical research, yet few have had more impact than induced pluripotent stem cells and modern-day genome editing. These technologies are providing unprecedented opportunities to improve physiological relevance of experimental models, further our understanding of developmental processes, and develop novel therapies. One of the research areas that benefit greatly from these technological advances is the three-dimensional human organoid culture systems that resemble human tissues morphologically and physiologically. Here we summarize the development of human pluripotent stem cells and their differentiation through organoid formation. We further discuss how genetic modifications, genome editing in particular, were applied to answer basic biological and biomedical questions using organoid cultures of both somatic and pluripotent stem cell origins. Finally, we discuss the potential challenges of applying human pluripotent stem cell and organoid technologies for safety and efficiency evaluation of emerging genome editing tools.
Topics: Cell Differentiation; Gene Editing; Genome, Human; Humans; Induced Pluripotent Stem Cells; Organoids; Pluripotent Stem Cells
PubMed: 33467883
DOI: 10.1177/1535370220985808 -
Chinese Medical Journal Apr 2018Since the advent of induced pluripotent stem cell (iPSC) technology a decade ago, enormous progress has been made in stem cell biology and regenerative medicine. Human... (Review)
Review
OBJECTIVE
Since the advent of induced pluripotent stem cell (iPSC) technology a decade ago, enormous progress has been made in stem cell biology and regenerative medicine. Human iPSCs have been widely used for disease modeling, drug discovery, and cell therapy development. In this review, we discuss the progress in applications of iPSC technology that are particularly relevant to drug discovery and regenerative medicine, and consider the remaining challenges and the emerging opportunities in the field.
DATA SOURCES
Articles in this review were searched from PubMed database from January 2014 to December 2017.
STUDY SELECTION
Original articles about iPSCs and cardiovascular diseases were included and analyzed.
RESULTS
iPSC holds great promises for human disease modeling, drug discovery, and stem cell-based therapy, and this potential is only beginning to be realized. However, several important issues remain to be addressed.
CONCLUSIONS
The recent availability of human cardiomyocytes derived from iPSCs opens new opportunities to build in vitro models of cardiac disease, screening for new drugs and patient-specific cardiac therapy.
Topics: Cardiovascular Diseases; Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Regenerative Medicine
PubMed: 29578130
DOI: 10.4103/0366-6999.228231 -
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 -
The EMBO Journal Jan 2015Recent studies link changes in energy metabolism with the fate of pluripotent stem cells (PSCs). Safe use of PSC derivatives in regenerative medicine requires an... (Review)
Review
Recent studies link changes in energy metabolism with the fate of pluripotent stem cells (PSCs). Safe use of PSC derivatives in regenerative medicine requires an enhanced understanding and control of factors that optimize in vitro reprogramming and differentiation protocols. Relative shifts in metabolism from naïve through "primed" pluripotent states to lineage-directed differentiation place variable demands on mitochondrial biogenesis and function for cell types with distinct energetic and biosynthetic requirements. In this context, mitochondrial respiration, network dynamics, TCA cycle function, and turnover all have the potential to influence reprogramming and differentiation outcomes. Shifts in cellular metabolism affect enzymes that control epigenetic configuration, which impacts chromatin reorganization and gene expression changes during reprogramming and differentiation. Induced PSCs (iPSCs) may have utility for modeling metabolic diseases caused by mutations in mitochondrial DNA, for which few disease models exist. Here, we explore key features of PSC energy metabolism research in mice and man and the impact this work is starting to have on our understanding of early development, disease modeling, and potential therapeutic applications.
Topics: Animals; Energy Metabolism; Humans; Mice; Pluripotent Stem Cells
PubMed: 25476451
DOI: 10.15252/embj.201490446 -
Clinical Pharmacology and Therapeutics Aug 2017The ability to generate patient/disease-specific human pluripotent stem cell (hPSC)-derived cardiomyocytes (hPSC-CMs) brings a unique value to the fields of cardiac... (Review)
Review
The ability to generate patient/disease-specific human pluripotent stem cell (hPSC)-derived cardiomyocytes (hPSC-CMs) brings a unique value to the fields of cardiac disease modeling, drug testing, drug discovery, and precision medicine. Further integration of emerging innovative technologies such as developmental-biology inspired differentiation into chamber-specific cardiomyocyte subtypes, genome-editing, tissue-engineering, and novel functional phenotyping methodologies should facilitate even more advanced investigations. Here, we review cornerstone concepts and recent highlights of hPSC-based cardiac disease modeling and drug testing.
Topics: Animals; Cardiovascular Agents; Drug Discovery; Drug Evaluation, Preclinical; Heart Diseases; Humans; Induced Pluripotent Stem Cells; Myocytes, Cardiac; Pluripotent Stem Cells
PubMed: 28718902
DOI: 10.1002/cpt.722 -
Best Practice & Research. Clinical... Dec 2015Although similar, mouse and human pancreatic development and beta cell physiology have significant differences. For this reason, mouse models present shortcomings that... (Review)
Review
Although similar, mouse and human pancreatic development and beta cell physiology have significant differences. For this reason, mouse models present shortcomings that can obscure the understanding of human diabetes pathology. Progress in the field of human pluripotent stem cell (hPSC) differentiation now makes it possible to derive unlimited numbers of human beta cells in vitro. This constitutes an invaluable approach to gain insight into human beta cell development and physiology and to generate improved disease models. Here we summarize the main differences in terms of development and physiology of the pancreatic endocrine cells between mouse and human, and describe the recent progress in modeling diabetes using hPSC. We highlight the need of developing more physiological hPSC-derived beta cell models and anticipate the future prospects of these approaches.
Topics: Animals; Cell Differentiation; Diabetes Mellitus; Gene Editing; Humans; Insulin-Secreting Cells; Islets of Langerhans Transplantation; Pluripotent Stem Cells
PubMed: 26696518
DOI: 10.1016/j.beem.2015.10.012