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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 -
Advances in Experimental Medicine and... 2019Pluripotent stem cells (PSCs), including embryonic stem cells and induced pluripotent stem cells, show heterogeneity with respect to their pluripotency, self-renewal... (Review)
Review
Pluripotent stem cells (PSCs), including embryonic stem cells and induced pluripotent stem cells, show heterogeneity with respect to their pluripotency, self-renewal ability, and other traits. PSC heterogeneity may exist among cell lines, among cells within a line, and among temporal states of individual cells. Both genetic and epigenetic factors can cause heterogeneity among cell lines. Heterogeneity among cells within a cell line may arise during long-term culturing even when a PSC cell line is derived from a single cell. Moreover, the expression levels of genes and proteins in PSCs fluctuate continuously at a frequency ranging from a few hours to a few days. Such heterogeneity decreases the reproducibility of research. Thus, methods related to the detection, reduction, and control of heterogeneity in experiments involving human PSCs need to be developed. Further, the presupposition that PSCs are highly heterogeneous should be taken into account by all researchers not only when they plan their own studies but also when they review the studies of other researchers in this field.
Topics: Cell Differentiation; Cell Line; Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells
PubMed: 31016596
DOI: 10.1007/978-3-030-11096-3_6 -
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 -
Trends in Molecular Medicine Sep 2019Pluripotent stem cells (PSCs) represent an attractive cell source for treating muscular dystrophies (MDs) since they easily allow for the generation of large numbers of... (Review)
Review
Pluripotent stem cells (PSCs) represent an attractive cell source for treating muscular dystrophies (MDs) since they easily allow for the generation of large numbers of highly regenerative myogenic progenitors. Using reprogramming technology, patient-specific PSCs have been derived for several types of MDs, and genome editing has allowed correction of mutations, opening the opportunity for their therapeutic application in an autologous transplantation setting. However, there has been limited progress on preclinical studies that validate the therapeutic potential of these gene corrected PSC-derived myogenic progenitors. In this review, we highlight the major research advances, challenges, and future prospects towards the development of PSC-based therapeutics for MDs.
Topics: Animals; Biomarkers; Cell Differentiation; Cell- and Tissue-Based Therapy; Disease Models, Animal; Gene Editing; Genetic Therapy; Humans; Induced Pluripotent Stem Cells; Muscular Dystrophies; Myoblasts, Cardiac; Pluripotent Stem Cells; Regeneration; Stem Cell Transplantation; Transgenes
PubMed: 31473142
DOI: 10.1016/j.molmed.2019.07.004 -
Transgenic Research Aug 2019Rats make an excellent model system for studying xenotransplantation since, like mice pluripotent stem cell lines, such as embryonic stem cells and induced pluripotent... (Review)
Review
Rats make an excellent model system for studying xenotransplantation since, like mice pluripotent stem cell lines, such as embryonic stem cells and induced pluripotent stem cells as well as gene knock-outs are also available for rats, besides rats have larger organs. The emergence of new genome-editing tools combined with stem cell technology, has revolutionized biomedical research including the field of regenerative medicine. The aim of this manuscript is to provide an overview of the recent progresses in stem cell-derived organ regeneration involving "gene knock-out" and "blastocyst complementation" in the rat model system. Knocking-out Pdx1, Foxn1, and Sall1 genes have successfully generated rat models lacking the pancreas, thymus, and kidney, respectively. When allogeneic (rat) or xenogeneic (mouse) pluripotent stem cells were microinjected into blastocyst-stage rat embryos that had been designed to carry a suitable organogenetic niche, devoid of specific organs, the complemented blastocysts were able to develop to full-term chimeric rat offspring containing stem cell-derived functional organs in their respective niches. Thus, organs with a tridimensional structure can be generated with pluripotent stem cells in vivo, accelerating regenerative medical research, which is crucial for organ-based transplantation therapies. However, to address ethical concerns, public consent after informed discussions is essential before production of human organs within domestic animals.
Topics: Animals; Embryonic Stem Cells; Humans; Mice; Organogenesis; Pluripotent Stem Cells; Rats; Stem Cell Transplantation
PubMed: 31254209
DOI: 10.1007/s11248-019-00161-2 -
Development, Growth & Differentiation Feb 2021Mouse embryonic stem cells (mESCs) are pluripotent stem cell populations derived from the preimplantation embryo and are used to study the differentiation of many types... (Review)
Review
Mouse embryonic stem cells (mESCs) are pluripotent stem cell populations derived from the preimplantation embryo and are used to study the differentiation of many types of somatic and germ cells in developing embryos. They are also used to study cell lineages of extraembryonic tissues, such as the trophectoderm (TE) and the primitive endoderm (PrE). mESC cultures are suitable systems for reproducing cellular and molecular events occurring during the differentiation of these cell types, such as changes in gene expression patterns, signaling events, and genome rearrangements although the consistency between the results obtained using mESCs and those of in vivo studies on embryos should be carefully taken into account. Since TE and PrE cells can be induced from mESCs in vitro, mESC cultures are useful systems to study differentiation of these cell lineages during development, if used appropriately. In addition, human pluripotent stem cells (hPSCs), such as human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs), are capable of generating extraembryonic lineages in vitro and are promising tools to study the differentiation of these lineages in the human embryo.
Topics: Animals; Cell Differentiation; Embryo, Mammalian; Humans; Pluripotent Stem Cells
PubMed: 33583019
DOI: 10.1111/dgd.12716 -
Cells May 2023Pluripotent stem cells are endless sources for in vitro engineering human tissues for regenerative medicine. Extensive studies have demonstrated that transcription... (Review)
Review
Pluripotent stem cells are endless sources for in vitro engineering human tissues for regenerative medicine. Extensive studies have demonstrated that transcription factors are the key to stem cell lineage commitment and differentiation efficacy. As the transcription factor profile varies depending on the cell type, global transcriptome analysis through RNA sequencing (RNAseq) has been a powerful tool for measuring and characterizing the success of stem cell differentiation. RNAseq has been utilized to comprehend how gene expression changes as cells differentiate and provide a guide to inducing cellular differentiation based on promoting the expression of specific genes. It has also been utilized to determine the specific cell type. This review highlights RNAseq techniques, tools for RNAseq data interpretation, RNAseq data analytic methods and their utilities, and transcriptomics-enabled human stem cell differentiation. In addition, the review outlines the potential benefits of the transcriptomics-aided discovery of intrinsic factors influencing stem cell lineage commitment, transcriptomics applied to disease physiology studies using patients' induced pluripotent stem cell (iPSC)-derived cells for regenerative medicine, and the future outlook on the technology and its implementation.
Topics: Humans; Regenerative Medicine; Transcriptome; Cell Differentiation; Pluripotent Stem Cells; Induced Pluripotent Stem Cells; Transcription Factors
PubMed: 37408278
DOI: 10.3390/cells12101442 -
Development, Growth & Differentiation Jan 2021Human pluripotent stem cells (PSCs) are used as a platform for therapeutic purposes such as cell transplantation therapy and drug discovery. Another motivation for... (Review)
Review
Human pluripotent stem cells (PSCs) are used as a platform for therapeutic purposes such as cell transplantation therapy and drug discovery. Another motivation for studying PSCs is to understand human embryogenesis and development. All cell types that make up the body tissues develop through defined trajectories during embryogenesis. For example, paraxial mesoderm is considered to differentiate into several cell types including skeletal muscle cells, chondrocytes, osteocytes, dermal fibroblasts, and tenocytes. Tenocytes are fibroblast cells that constitute the tendon. The step-wise narrowing fate decisions of paraxial mesoderm in the embryo have been modeled in vitro using PSCs; however, deriving tenocytes from human-induced PSCs and their application in cell therapy have long been challenging. PSC-derived tenocytes can be used for a source of cell transplantation to treat a damaged or ruptured tendon due to injury, disorder, or aging. In this review, we discuss the latest research findings on the use of PSCs for studying the biology of tenocyte development and their application in therapeutic settings.
Topics: Cell Differentiation; Humans; Pluripotent Stem Cells; Tenocytes
PubMed: 33270251
DOI: 10.1111/dgd.12702 -
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 -
Cell Proliferation Aug 2022The human plutiripotent stem cell registry (hPSCreg) is a global database for human embryonic and induced pluripotent stem cells (hESC, hiPSC). The publicly accessible... (Review)
Review
The human plutiripotent stem cell registry (hPSCreg) is a global database for human embryonic and induced pluripotent stem cells (hESC, hiPSC). The publicly accessible Registry (https://hpscreg.eu) was set up to provide a transparent resource of quality-assessed hPSC lines as well as to increase reproducibility of research and interoperability of data. OBJECTIVES: In this review, we describe the establishment of the Registry and its mission, its development into a knowledgebase for hPSC and the current status of hPSC-focussed databases. The data categories available in hPSCreg are detailed. In addition, sharing and hurdles to data sharing on a global level are described. CONCLUSIONS: An outlook is provided on the establishment of digital representatives of donors using hybrids of data and hPSC-based biological models, and how this can also be used to reposition databases as mediators between donors and researchers.
Topics: Cell Differentiation; Databases, Factual; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells; Registries; Reproducibility of Results
PubMed: 35522426
DOI: 10.1111/cpr.13238