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Current Cardiology Reports May 2023Heart failure leads to high mortality. The failing myocardium cannot often be rescued as heart regeneration is mostly compromised by disease progress. Stem cell therapy... (Review)
Review
PURPOSE OF REVIEW
Heart failure leads to high mortality. The failing myocardium cannot often be rescued as heart regeneration is mostly compromised by disease progress. Stem cell therapy is a strategy under development to replace the impaired myocardium for recovery after heart injury.
RECENT FINDINGS
Many studies have provided evidence of the beneficial effects of pluripotent stem cell-derived cardiomyocyte (CM) implantation into diseased rodent hearts, but there are still many challenges and limitations to replicating the same effects in large animal models for preclinical validation. In this review, we summarize progress in the use of pluripotent stem cell-derived CMs in large animal models based on three key parameters: species selection, cell source, and delivery. Most importantly, we discuss the current limitations and challenges that need to be solved to advance this technology to the translational stage.
Topics: Animals; Humans; Myocytes, Cardiac; Induced Pluripotent Stem Cells; Pluripotent Stem Cells; Models, Animal; Regeneration; Cell Differentiation; Disease Models, Animal
PubMed: 37074564
DOI: 10.1007/s11886-023-01857-y -
Results and Problems in Cell... 2024All somatic cells develop from the epiblast, which occupies the upper layer of two-layered embryos and in most mammals is formed after the implantation stage but before...
All somatic cells develop from the epiblast, which occupies the upper layer of two-layered embryos and in most mammals is formed after the implantation stage but before gastrulation initiates. Once the epiblast is established, the epiblast cells begin to develop into various somatic cells via large-scale cell reorganization, namely, gastrulation. Different pluripotent stem cell lines representing distinct stages of embryogenesis have been established: mouse embryonic stem cells (mESCs), human embryonic stem cells (hESCs), and mouse epiblast stem cells (EpiSCs), which represent the preimplantation stage inner cell mass, an early post-implantation stage epiblast, and a later-stage epiblast, respectively. Together, these cell lines provide excellent in vitro models of cell regulation before somatic cells develop. This chapter addresses these early developmental stages.
Topics: Animals; Mice; Humans; Embryonic Stem Cells; Cell Differentiation; Pluripotent Stem Cells; Germ Layers; Cell Line; Mammals
PubMed: 38509249
DOI: 10.1007/978-3-031-39027-2_1 -
International Journal of Hematology Apr 2010Embryonic stem cells (ESCs) can differentiate into various types of hematopoietic cells (HPCs) when placed in an appropriate environment. Various methods for the... (Review)
Review
Embryonic stem cells (ESCs) can differentiate into various types of hematopoietic cells (HPCs) when placed in an appropriate environment. Various methods for the differentiation of ESCs into specific HPC lineages have been developed using mouse ESCs. These ESC-differentiation methods have been utilized also as an in vitro model to investigate hematopoiesis in embryos and they provided critical perceptions into it. These methods have been adapted for use with human ESCs, which have the possibility of being employed in regenerative medicine; further improvement of these methods may lead to the efficient production of HPCs for use in transfusions. The generation of transplantable hematopoietic stem cells is a medical goal that is still difficult to achieve. Recently, induced pluripotent stem (iPS) cells have been established from differentiated cells. Thereby, iPS cells have expanded further possibilities of the use of pluripotent stem cell lines in clinical application. Indeed, iPS cells have been established from cells with disease genes and those which have undergone reprogramming and targeting have generated phenotypically normal HPCs. Here, we mainly summarize the recent progress in research on hematopoiesis conducted with ESCs and iPS cells.
Topics: Animals; Cell Lineage; Hematopoiesis; Humans; Pluripotent Stem Cells; Regeneration
PubMed: 20169427
DOI: 10.1007/s12185-010-0519-7 -
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 -
Annual Review of Cell and Developmental... 2013In the past decade, significant progress has been made in understanding both microRNA function and cellular pluripotency. Here we review the intersection of these two... (Review)
Review
In the past decade, significant progress has been made in understanding both microRNA function and cellular pluripotency. Here we review the intersection of these two exciting fields. While microRNAs are not required for the establishment and maintenance of pluripotency in early development and cell culture, respectively, they are critically important in the regulation of the cell cycle structure of pluripotent stem cells as well as the silencing of the pluripotency program upon differentiation. Pluripotent cells, both in vivo and in vitro, dominantly express a single family of microRNAs, which can promote the reprogramming of a somatic cell back to a pluripotent state. Here, we review the known mechanisms by which these and other microRNAs regulate the different aspects of the pluripotent stem cell program in both mouse and human.
Topics: Animals; Cell Culture Techniques; Cell Differentiation; Embryonic Stem Cells; Humans; Mice; MicroRNAs; Pluripotent Stem Cells
PubMed: 23875649
DOI: 10.1146/annurev-cellbio-101512-122343 -
CNS & Neurological Disorders Drug... Dec 2013A critical step in the development of effective therapeutics to treat Parkinson's disease (PD) is the identification of molecular pathogenic mechanisms underlying this... (Review)
Review
A critical step in the development of effective therapeutics to treat Parkinson's disease (PD) is the identification of molecular pathogenic mechanisms underlying this chronically progressive neurodegenerative disease. However, while animal models have provided valuable information about the molecular basis of PD, the lack of faithful cellular and animal models that recapitulate human pathophysiology is delaying the development of new therapeutics. The reprogramming of somatic cells to induced pluripotent stem cells (iPSC) using delivery of defined combinations of transcription factors is a groundbreaking discovery that opens great opportunities for modeling human diseases, including PD, since iPSC can be generated from patients and differentiated into disease-relevant cell types, which would capture the patients' genetic complexity. Furthermore, human iPSC-derived neuronal models offer unprecedented access to early stages of the disease, allowing the investigation of the events that initiate the pathologic process in PD. Recently, human iPSC-derived neurons from patients with familial and sporadic PD have been generated and importantly they recapitulate some PD-related cell phenotypes, including abnormal α-synuclein accumulation in vitro, and alterations in the autophagy machinery. This review highlights the current PD iPSC-based models and discusses the potential future research directions of this field.
Topics: Animals; Humans; Induced Pluripotent Stem Cells; Neural Stem Cells; Parkinson Disease; Pluripotent Stem Cells; Stem Cell Transplantation
PubMed: 24040813
DOI: No ID Found -
The Journal of Experimental Medicine Dec 2010The era of induced pluripotent stem (iPS) cells carries with it the promise of virtually unlimited sources of autologous cells for regenerative medicine. However,... (Review)
Review
The era of induced pluripotent stem (iPS) cells carries with it the promise of virtually unlimited sources of autologous cells for regenerative medicine. However, efficiently differentiating iPS cells into fully functional mature cell types remains challenging. A new study reporting the formation of fully functional platelets from human iPS (hiPS) cells improves upon recent efforts to generate this enucleated cell type, which remains in high demand for therapeutic transfusions. Notably, their lack of nucleus renders platelets unable to retain the pluripotent or tumorigenic properties of iPS cells.
Topics: Animals; Blood Platelets; Cell Differentiation; Gene Expression Regulation; Humans; Induced Pluripotent Stem Cells; Platelet Transfusion; Pluripotent Stem Cells; Proto-Oncogene Proteins c-myc; Thrombocytopenia
PubMed: 21173109
DOI: 10.1084/jem.20102428 -
Circulation Research Jan 2014The discovery of human pluripotent stem cells (hPSCs), including both human embryonic stem cells and human-induced pluripotent stem cells, has opened up novel paths for... (Review)
Review
The discovery of human pluripotent stem cells (hPSCs), including both human embryonic stem cells and human-induced pluripotent stem cells, has opened up novel paths for a wide range of scientific studies. The capability to direct the differentiation of hPSCs into functional cardiomyocytes has provided a platform for regenerative medicine, development, tissue engineering, disease modeling, and drug toxicity testing. Despite exciting progress, achieving the optimal benefits has been hampered by the immature nature of these cardiomyocytes. Cardiac maturation has long been studied in vivo using animal models; however, finding ways to mature hPSC cardiomyocytes is only in its initial stages. In this review, we discuss progress in promoting the maturation of the hPSC cardiomyocytes, in the context of our current knowledge of developmental cardiac maturation and in relation to in vitro model systems such as rodent ventricular myocytes. Promising approaches that have begun to be examined in hPSC cardiomyocytes include long-term culturing, 3-dimensional tissue engineering, mechanical loading, electric stimulation, modulation of substrate stiffness, and treatment with neurohormonal factors. Future studies will benefit from the combinatorial use of different approaches that more closely mimic nature's diverse cues, which may result in broader changes in structure, function, and therapeutic applicability.
Topics: Animals; Cell Differentiation; Cell Engineering; Cells, Cultured; Genetic Engineering; Humans; Induced Pluripotent Stem Cells; Models, Animal; Myocytes, Cardiac; Pluripotent Stem Cells; Time Factors
PubMed: 24481842
DOI: 10.1161/CIRCRESAHA.114.300558 -
Stem Cells (Dayton, Ohio) Mar 2020As new applications for human pluripotent stem cell-derived organoids in drug screenings and tissue replacement therapies emerge, there is a need to examine the... (Review)
Review
As new applications for human pluripotent stem cell-derived organoids in drug screenings and tissue replacement therapies emerge, there is a need to examine the mechanisms of tissue injury and repair recently reported for various organoid models. In most cases, organoids contain the main cell types and tissues present in human organs, spatially arranged in a manner that largely resembles the architecture of the organ. Depending on the differentiation protocol used, variations may exist in cell type ratios relative to the organ of reference, and certain tissues, including some parenchymal components and the endothelium, might be poorly represented, or lacking altogether. Despite those caveats, recent studies have shown that organoid tissue injury recapitulates major events and histopathological features of damaged human tissues. In particular, major mechanisms of parenchyma cell damage and interstitial fibrosis can be reproduced with remarkable faithfulness. Although further validation remains to be done in order to establish the relevance of using organoid for either mechanistic studies or drug assays, this technology is becoming a promising tool for the study of human tissue homeostasis, injury, and repair.
Topics: Cell Differentiation; Fibrosis; Humans; Organoids; Pluripotent Stem Cells
PubMed: 31778256
DOI: 10.1002/stem.3131 -
Advanced Drug Delivery Reviews Jan 2016Regenerative medicine, including preclinical studies in large animal models and tissue engineering approaches as well as innovative assays for drug discovery, will... (Review)
Review
Regenerative medicine, including preclinical studies in large animal models and tissue engineering approaches as well as innovative assays for drug discovery, will require the constant supply of hPSC-derived cardiomyocytes and other functional progenies. Respective cell production processes must be robust, economically viable and ultimately GMP-compliant. Recent research has enabled transition of lab scale protocols for hPSC expansion and cardiomyogenic differentiation towards more controlled processing in industry-compatible culture platforms. Here, advanced strategies for the cultivation and differentiation of hPSCs will be reviewed by focusing on stirred bioreactor-based techniques for process upscaling. We will discuss how cardiomyocyte mass production might benefit from recent findings such as cell expansion at the cardiovascular progenitor state. Finally, remaining challenges will be highlighted, specifically regarding three dimensional (3D) hPSC suspension culture and critical safety issues ahead of clinical translation.
Topics: Animals; Cell Culture Techniques; Cell Differentiation; Humans; Myocytes, Cardiac; Pluripotent Stem Cells; Stem Cell Research; Tissue Engineering; Wnt Signaling Pathway
PubMed: 26658242
DOI: 10.1016/j.addr.2015.11.016