-
Current Opinion in Organ Transplantation Dec 2015In this review, we summarize the current status of clinical trials using therapeutic cells produced from human embryonic stem cells (hESCs) and human induced pluripotent... (Review)
Review
PURPOSE OF REVIEW
In this review, we summarize the current status of clinical trials using therapeutic cells produced from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). We also discuss combined cell and gene therapy via correction of defined mutations in human pluripotent stem cells and provide commentary on key obstacles facing widescale clinical adoption of pluripotent stem cell-based therapy.
RECENT FINDINGS
Initial data suggest that hESC/hiPSC-derived cell products used for retinal repair and spinal cord injury are safe for human use. Early-stage studies for treatment of cardiac injury and diabetes are also in progress. However, there remain key concerns regarding the safety and efficacy of these cells that need to be addressed in additional well designed clinical trials. Advances using the clustered regulatory interspaced short palindromic repeats (CRISPR)/Cas9 gene-editing system offer an improved tool for more rapid and on-target gene correction of genetic diseases. Combined gene and cell therapy using human pluripotent stem cells may provide an additional curative approach for disabling or lethal genetic and degenerative diseases wherein there are currently limited therapeutic opportunities.
SUMMARY
Human pluripotent stem cells are emerging as a promising tool to produce cells and tissues suitable for regenerative therapy for a variety of genetic and degenerative diseases.
Topics: Animals; Clinical Trials as Topic; Genetic Therapy; Human Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Regenerative Medicine; Stem Cell Transplantation
PubMed: 26536430
DOI: 10.1097/MOT.0000000000000244 -
Stem Cell Reports Aug 2023The Human Pluripotent Stem Cell Registry established a database of clinical studies using human pluripotent stem cells (PSCs) as starting material for cell therapies.... (Review)
Review
The Human Pluripotent Stem Cell Registry established a database of clinical studies using human pluripotent stem cells (PSCs) as starting material for cell therapies. Since 2018, we have observed a switch toward human induced pluripotent stem cells (iPSCs) from human embryonic stem cells. However, rather than using iPSCs for personalized medicines, allogeneic approaches dominate. Most treatments target ophthalmopathies, and genetically modified iPSCs are used to generate tailored cells. We observe a lack of standardization and transparency about the PSCs lines used, characterization of the PSC-derived cells, and the preclinical models and assays applied to show efficacy and safety.
Topics: Humans; Induced Pluripotent Stem Cells; Cell Differentiation; Pluripotent Stem Cells; Human Embryonic Stem Cells; Cell- and Tissue-Based Therapy
PubMed: 37028422
DOI: 10.1016/j.stemcr.2023.03.005 -
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 -
Stem Cell Research May 2021The Korea National Stem Cell Bank has been banking pluripotent stem cell (PSC) lines since 2012. Quality-controlled and ethically sourced cell lines were developed for...
The Korea National Stem Cell Bank has been banking pluripotent stem cell (PSC) lines since 2012. Quality-controlled and ethically sourced cell lines were developed for distribution. Currently (as of 2020), among the 69 deposited lines, 4 research-grade human embryonic stem cell (hESC) lines and 19 induced pluripotent stem cell (iPSC) lines have been distributed. Good manufacturing practices (GMP)-compliant homozygous iPSC lines for regenerative medicine with homozygous HLA haplotypes that cover 51% of the Korean population have been deposited as well. To ensure the quality of the cell lines, we performed eighteen different quality tests on the identity, sterility, consistency, stability and safety of the cell lines. Regarding genetic stability, we are collecting SNPchip, WES, Methyl-seq, and RNA-seq data, which are open to the public.
Topics: Cell Line; Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells; Republic of Korea
PubMed: 33714852
DOI: 10.1016/j.scr.2021.102270 -
Journal of Cardiology Nov 2020Pluripotent stem cells (PSCs), which include embryonic and induced pluripotent stem cells (ESCs and iPSCs, respectively), have great potential in regenerative medicine... (Review)
Review
Pluripotent stem cells (PSCs), which include embryonic and induced pluripotent stem cells (ESCs and iPSCs, respectively), have great potential in regenerative medicine for heart diseases due to their virtually unlimited cardiogenic capacity. Many preclinical studies have described the functional benefits after transplantation of PSC-derived cardiomyocytes (PSC-CMs). However, transient ventricular arrhythmias were detected after injection into non-human primates and swine ischemic hearts; as engrafted PSC-CMs form an electrical coupling between host and graft, the immature characteristics of PSC-CMs may serve as an ectopic pacemaker. We are entering a critical time in the development of novel therapies using PSC-CMs, with the recent first clinical trial using human iPSC-CMs (hiPSC-CMs) being launched in Japan. In this review, we summarize the updated knowledge, perspectives, and limitations of PSC-CMs for heart regeneration.
Topics: Animals; Cell Differentiation; Heart; Humans; Myocytes, Cardiac; Pluripotent Stem Cells; Regeneration
PubMed: 32690435
DOI: 10.1016/j.jjcc.2020.03.013 -
Trends in Cell Biology May 2017The advent of human pluripotent stem cell (hPSC) biology has opened unprecedented opportunities for the use of tissue engineering to generate human cardiac tissue for in... (Review)
Review
The advent of human pluripotent stem cell (hPSC) biology has opened unprecedented opportunities for the use of tissue engineering to generate human cardiac tissue for in vitro study. Engineering cardiac constructs that recapitulate human development and disease requires faithful recreation of the cardiac niche in vitro. Here we discuss recent progress in translating the in vivo cardiac microenvironment into PSC models of the human heart. We review three key physiologic features required to recreate the cardiac niche and facilitate normal cardiac differentiation and maturation: the biochemical, biophysical, and bioelectrical signaling cues. Finally, we discuss key barriers that must be overcome to fulfill the promise of stem cell biology in preclinical applications and ultimately in clinical practice.
Topics: Cellular Microenvironment; Disease; Humans; Models, Biological; Physiological Phenomena; Pluripotent Stem Cells
PubMed: 28007424
DOI: 10.1016/j.tcb.2016.11.010 -
International Journal of Molecular... Jan 2021For obvious reasons, such as, e.g., ethical concerns or sample accessibility, model systems are of highest importance to study the underlying molecular mechanisms of... (Review)
Review
For obvious reasons, such as, e.g., ethical concerns or sample accessibility, model systems are of highest importance to study the underlying molecular mechanisms of human maladies with the aim to develop innovative and effective therapeutic strategies. Since many years, animal models and highly proliferative transformed cell lines are successfully used for disease modelling, drug discovery, target validation, and preclinical testing. Still, species-specific differences regarding genetics and physiology and the limited suitability of immortalized cell lines to draw conclusions on normal human cells or specific cell types, are undeniable shortcomings. The progress in human pluripotent stem cell research now allows the growth of a virtually limitless supply of normal and DNA-edited human cells, which can be differentiated into various specific cell types. However, cells in the human body never fulfill their functions in mono-lineage isolation and diseases always develop in complex multicellular ecosystems. The recent advances in stem cell-based 3D organoid technologies allow a more accurate in vitro recapitulation of human pathologies. Embryoids are a specific type of such multicellular structures that do not only mimic a single organ or tissue, but the entire human conceptus or at least relevant components of it. Here we briefly describe the currently existing in vitro human embryo models and discuss their putative future relevance for disease modelling and drug discovery.
Topics: Animals; Cell Culture Techniques; Cell Differentiation; Cells, Cultured; Drug Discovery; Embryo, Mammalian; Embryonic Development; Human Embryonic Stem Cells; Humans; Models, Animal; Organoids; Pluripotent Stem Cells
PubMed: 33440617
DOI: 10.3390/ijms22020637 -
Integrative Biology : Quantitative... Dec 2013Geometric factors including the size, shape, density, and spacing of pluripotent stem cell colonies play a significant role in the maintenance of pluripotency and in...
Geometric factors including the size, shape, density, and spacing of pluripotent stem cell colonies play a significant role in the maintenance of pluripotency and in cell fate determination. These factors are impossible to control using standard tissue culture methods. As such, there can be substantial batch-to-batch variability in cell line maintenance and differentiation yield. Here, we demonstrate a simple, robust technique for pluripotent stem cell expansion and cardiomyocyte differentiation by patterning cell colonies with a silicone stencil. We have observed that patterning human induced pluripotent stem cell (hiPSC) colonies improves the uniformity and repeatability of their size, density, and shape. Uniformity of colony geometry leads to improved homogeneity in the expression of pluripotency markers SSEA4 and Nanog as compared with conventional clump passaging. Patterned cell colonies are capable of undergoing directed differentiation into spontaneously beating cardiomyocyte clusters with improved yield and repeatability over unpatterned cultures seeded either as cell clumps or uniform single cell suspensions. Circular patterns result in a highly repeatable 3D ring-shaped band of cardiomyocytes which electrically couple and lead to propagating contraction waves around the ring. Because of these advantages, geometrically patterning stem cells using stencils may offer greater repeatability from batch-to-batch and person-to-person, an increase in differentiation yield, a faster experimental workflow, and a simpler protocol to communicate and follow. Furthermore, the ability to control where cardiomyocytes arise across a culture well during differentiation could greatly aid the design of electrophysiological assays for drug-screening.
Topics: Cell Culture Techniques; Cell Differentiation; Homeodomain Proteins; Humans; Microscopy, Fluorescence; Myocytes, Cardiac; Nanog Homeobox Protein; Pluripotent Stem Cells; Stage-Specific Embryonic Antigens
PubMed: 24141327
DOI: 10.1039/c2ib20191g -
Cell Stem Cell Mar 2022Human naive pluripotent stem cells have the remarkable ability to generate blastoids comprising trophectoderm, epiblast, and hypoblast-like cells. In this issue,...
Human naive pluripotent stem cells have the remarkable ability to generate blastoids comprising trophectoderm, epiblast, and hypoblast-like cells. In this issue, Taubenschmid-Stowers et al. (2022) show that human naive pluripotent stem cell cultures contain cells that resemble the 8-cell human embryo, providing a model to study zygotic genome activation.
Topics: Embryo, Mammalian; Germ Layers; Humans; Pluripotent Stem Cells
PubMed: 35245463
DOI: 10.1016/j.stem.2022.01.015 -
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