-
Regenerative Medicine Feb 2021
Topics: Cell Differentiation; Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells
PubMed: 33650442
DOI: 10.2217/rme-2021-0013 -
Cell Proliferation Aug 2022The unlimited proliferative capacity of human pluripotent stem cells (hPSCs) fortifies it as one of the most attractive sources for cell therapy application in diabetes.... (Review)
Review
The unlimited proliferative capacity of human pluripotent stem cells (hPSCs) fortifies it as one of the most attractive sources for cell therapy application in diabetes. In the past two decades, vast research efforts have been invested in developing strategies to differentiate hPSCs into clinically suitable insulin-producing endocrine cells or functional beta cells (β cells). With the end goal being clinical translation, it is critical for hPSCs and insulin-producing β cells to be derived, handled, stored, maintained and expanded with clinical compliance. This review focuses on the key processes and guidelines for clinical translation of human induced pluripotent stem cell (hiPSC)-derived β cells for diabetes cell therapy. Here, we discuss the (1) key considerations of manufacturing clinical-grade hiPSCs, (2) scale-up and differentiation of clinical-grade hiPSCs into β cells in clinically compliant conditions and (3) mandatory quality control and product release criteria necessitated by various regulatory bodies to approve the use of the cell-based products.
Topics: Cell Differentiation; Diabetes Mellitus; Humans; Induced Pluripotent Stem Cells; Insulins; Pluripotent Stem Cells
PubMed: 35474596
DOI: 10.1111/cpr.13232 -
BMB Reports Oct 2021Human pluripotent stem cells (hPSCs) include human embryonic stem cells (hESCs) derived from blastocysts and human induced pluripotent stem cells (hiPSCs) generated from...
Human pluripotent stem cells (hPSCs) include human embryonic stem cells (hESCs) derived from blastocysts and human induced pluripotent stem cells (hiPSCs) generated from somatic cell reprogramming. Due to their self-renewal ability and pluripotent differentiation potential, hPSCs serve as an excellent experimental platform for human development, disease modeling, drug screening, and cell therapy. Traditionally, hPSCs were considered to form a homogenous population. However, recent advances in single cell technologies revealed a high degree of variability between individual cells within a hPSC population. Different types of heterogeneity can arise by genetic and epigenetic abnormalities associated with long-term in vitro culture and somatic cell reprogramming. These variations initially appear in a rare population of cells. However, some cancer-related variations can confer growth advantages to the affected cells and alter cellular phenotypes, which raises significant concerns in hPSC applications. In contrast, other types of heterogeneity are related to intrinsic features of hPSCs such as asynchronous cell cycle and spatial asymmetry in cell adhesion. A growing body of evidence suggests that hPSCs exploit the intrinsic heterogeneity to produce multiple lineages during differentiation. This idea offers a new concept of pluripotency with single cell heterogeneity as an integral element. Collectively, single cell heterogeneity is Janus-faced in hPSC function and application. Harmful heterogeneity has to be minimized by improving culture conditions and screening methods. However, other heterogeneity that is integral for pluripotency can be utilized to control hPSC proliferation and differentiation. [BMB Reports 2021; 54(10): 505-515].
Topics: Cell Culture Techniques; Cell Differentiation; Cell Line; Epigenomics; Genetic Heterogeneity; Genetics; Human Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells; Single-Cell Analysis
PubMed: 34488931
DOI: 10.5483/BMBRep.2021.54.10.094 -
Cells Nov 2020Neurodegenerative diseases are characterized by irreversible cell damage, loss of neuronal cells and limited regeneration potential of the adult nervous system.... (Review)
Review
Neurodegenerative diseases are characterized by irreversible cell damage, loss of neuronal cells and limited regeneration potential of the adult nervous system. Pluripotent stem cells are capable of differentiating into the multitude of cell types that compose the central and peripheral nervous systems and so have become the major focus of cell replacement therapies for the treatment of neurological disorders. Human embryonic stem cell (hESC) and human induced pluripotent stem cell (hiPSC)-derived cells have both been extensively studied as cell therapies in a wide range of neurodegenerative disease models in rodents and non-human primates, including Parkinson's disease, stroke, epilepsy, spinal cord injury, Alzheimer's disease, multiple sclerosis and pain. In this review, we discuss the latest progress made with stem cell therapies targeting these pathologies. We also evaluate the challenges in clinical application of human pluripotent stem cell (hPSC)-based therapies including risk of oncogenesis and tumor formation, immune rejection and difficulty in regeneration of the heterogeneous cell types composing the central nervous system.
Topics: Animals; Cell- and Tissue-Based Therapy; Humans; Neurodegenerative Diseases; Pluripotent Stem Cells; Regenerative Medicine
PubMed: 33233861
DOI: 10.3390/cells9112517 -
Cytometry. Part a : the Journal of the... Jan 2018Pluripotent stem cells have the capacity to grow indefinitely in culture and differentiate into derivatives of the three germ layers. These properties underpin their... (Review)
Review
Pluripotent stem cells have the capacity to grow indefinitely in culture and differentiate into derivatives of the three germ layers. These properties underpin their potential to be used in regenerative medicine. Originally derived from early embryos, pluripotent stem cells can now be derived by reprogramming an adult cell back to a pluripotent state. Companion animals such as horses, dogs, and cats suffer from many injuries and diseases for which regenerative medicine may offer new treatments. As many of the injuries and diseases are similar to conditions in humans the use of companion animals for the experimental and clinical testing of stem cell and regenerative medicine products would provide relevant animal models for the translation of therapies to the human field. In order to fully utilize companion animal pluripotent stem cells robust, standardized methods of characterization must be developed to ensure that safe and effective treatments can be delivered. In this review we discuss the methods that are available for characterizing pluripotent stem cells and the techniques that have been applied in cells from companion animals. We describe characteristics which have been described consistently across reports as well as highlighting discrepant results. Significant steps have been made to define the in vitro culture requirements and drive lineage specific differentiation of pluripotent stem cells in companion animal species. However, additional basic research to compare pluripotent stem cell types and define characteristics of pluripotency in companion animal species is still required. © 2017 International Society for Advancement of Cytometry.
Topics: Animals; Cats; Cell Culture Techniques; Cell Differentiation; Cell Lineage; Disease Models, Animal; Dogs; Embryonic Stem Cells; Horses; Humans; Induced Pluripotent Stem Cells; Models, Animal; Pets; Pluripotent Stem Cells; Regenerative Medicine; Translational Research, Biomedical
PubMed: 28678404
DOI: 10.1002/cyto.a.23163 -
Stem Cell Reviews and Reports Oct 2023With the vast number of chemicals in commerce, higher throughput strategies are needed to inform risk assessment. The field of toxicology is therefore moving away from... (Review)
Review
With the vast number of chemicals in commerce, higher throughput strategies are needed to inform risk assessment. The field of toxicology is therefore moving away from traditional in vivo guideline studies towards in vitro new approach methodologies. There has been a great push for such a shift in the field of developmental neurotoxicity, where there is a particular lack of data. A battery of in vitro new approach methodologies has thus been developed to help fill this gap. Included in this battery are assays for numerous processes critical to neurodevelopment, such as proliferation, migration, and synaptogenesis. The current battery of developmental neurotoxicity new approach methodologies still lacks recapitulation of several critical neurodevelopmental processes, including development of neuronal subtypes. With their pluripotency, alongside other advantages, pluripotent stem cells (PSCs) are uniquely suited to address questions of developmental neurotoxicity, as they can recapitulate the different stages of human in vivo neurodevelopment. Among the various neuronal subtypes, development of dopaminergic neurons (DA) is perhaps the best understood and several approaches exist to differentiate PSCs into DA. Herein we review these approaches and propose utilizing PSCs for screening of the impact of environmental chemicals on development of DA. Related techniques and gaps in knowledge are also addressed.
Topics: Humans; Dopaminergic Neurons; Neural Stem Cells; Induced Pluripotent Stem Cells; Neurotoxicity Syndromes; Pluripotent Stem Cells
PubMed: 37273171
DOI: 10.1007/s12015-023-10555-9 -
International Journal of Molecular... Feb 2015Stem cells are unique pools of cells that are crucial for embryonic development and maintenance of adult tissue homeostasis. The landmark Nobel Prize winning research by... (Review)
Review
Stem cells are unique pools of cells that are crucial for embryonic development and maintenance of adult tissue homeostasis. The landmark Nobel Prize winning research by Yamanaka and colleagues to induce pluripotency in somatic cells has reshaped the field of stem cell research. The complications related to the usage of pluripotent embryonic stem cells (ESCs) in human medicine, particularly ESC isolation and histoincompatibility were bypassed with induced pluripotent stem cell (iPSC) technology. The human iPSCs can be used for studying embryogenesis, disease modeling, drug testing and regenerative medicine. iPSCs can be diverted to different cell lineages using small molecules and growth factors. In this review we have focused on iPSC differentiation towards cardiac and neuronal lineages. Moreover, we deal with the use of iPSCs in regenerative medicine and modeling diseases like myocardial infarction, Timothy syndrome, dilated cardiomyopathy, Parkinson's, Alzheimer's and Huntington's disease. Despite the promising potential of iPSCs, genome contamination and low efficacy of cell reprogramming remain significant challenges.
Topics: Animals; Cell Differentiation; Cellular Reprogramming; Humans; Induced Pluripotent Stem Cells; Myocytes, Cardiac; Neurodegenerative Diseases; Neurons; Regenerative Medicine
PubMed: 25689424
DOI: 10.3390/ijms16024043 -
Stem Cell Reports Jan 2024Driving efficient and pure skeletal muscle cell differentiation from pluripotent stem cells (PSCs) has been challenging. Here, we report an optimized protocol that...
Driving efficient and pure skeletal muscle cell differentiation from pluripotent stem cells (PSCs) has been challenging. Here, we report an optimized protocol that generates skeletal muscle progenitor cells with high efficiency and purity in a short period of time. Human induced PSCs (hiPSCs) and murine embryonic stem cells (mESCs) were specified into the mesodermal myogenic fate using distinct and species-specific protocols. We used a specific maturation medium to promote the terminal differentiation of both human and mouse myoblast populations, and generated myotubes associated with a large pool of cell-cycle arrested PAX7 cells. We also show that myotube maturation is modulated by dish-coating properties, cell density, and percentage of myogenic progenitor cells. Given the high efficiency in the generation of myogenic progenitors and differentiated myofibers, this protocol provides an attractive strategy for tissue engineering, modeling of muscle dystrophies, and evaluation of new therapeutic approaches in vitro.
Topics: Humans; Animals; Mice; Cells, Cultured; Pluripotent Stem Cells; Muscle Fibers, Skeletal; Induced Pluripotent Stem Cells; Cell Differentiation; Muscle Development; Muscle, Skeletal
PubMed: 38101399
DOI: 10.1016/j.stemcr.2023.11.002 -
Cells Dec 2019Heart diseases such as myocardial infarction and myocardial ischemia are paroxysmal and fatal in clinical practice. Cardiomyocytes (CMs) differentiated from human... (Review)
Review
Heart diseases such as myocardial infarction and myocardial ischemia are paroxysmal and fatal in clinical practice. Cardiomyocytes (CMs) differentiated from human pluripotent stem cells provide a promising approach to myocardium regeneration therapy. Identifying the maturity level of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is currently the main challenge for pathophysiology and therapeutics. In this review, we describe current maturity indicators for cardiac microtissue and microdevice cultivation technologies that accelerate cardiac maturation. It may provide insights into regenerative medicine, drug cardiotoxicity testing, and preclinical safety testing.
Topics: Animals; Cell Differentiation; Humans; Myocytes, Cardiac; Pluripotent Stem Cells; Stem Cell Transplantation; Stem Cells; Ventricular Remodeling
PubMed: 31861463
DOI: 10.3390/cells9010009 -
Cell Stem Cell Sep 2019Advances in our understanding of cardiovascular development have provided a roadmap for the directed differentiation of human pluripotent stem cells (hPSCs) to the major... (Review)
Review
Advances in our understanding of cardiovascular development have provided a roadmap for the directed differentiation of human pluripotent stem cells (hPSCs) to the major cell types found in the heart. In this Perspective, we review the state of the field in generating and maturing cardiovascular cells from hPSCs based on our fundamental understanding of heart development. We then highlight their applications for studying human heart development, modeling disease-performing drug screening, and cell replacement therapy. With the advancements highlighted here, the promise that hPSCs will deliver new treatments for degenerative and debilitating diseases may soon be fulfilled.
Topics: Aldehyde Dehydrogenase 1 Family; Cardiovascular Diseases; Cell Culture Techniques; Cell Differentiation; Humans; Induced Pluripotent Stem Cells; Myocytes, Cardiac; Pluripotent Stem Cells; Retinal Dehydrogenase; Stem Cell Transplantation
PubMed: 31491395
DOI: 10.1016/j.stem.2019.07.010