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Future Medicinal Chemistry Jun 2019Most neurodegenerative diseases are characterized by a complex and mostly still unresolved pathology. This fact, together with the lack of reliable disease models, has... (Review)
Review
Most neurodegenerative diseases are characterized by a complex and mostly still unresolved pathology. This fact, together with the lack of reliable disease models, has precluded the development of effective therapies counteracting the disease progression. The advent of human pluripotent stem cells has revolutionized the field allowing the generation of disease-relevant neural cell types that can be used for disease modeling, drug screening and, possibly, cell transplantation purposes. In this Review, we discuss the applications of human pluripotent stem cells, the development of efficient protocols for the derivation of the different neural cells and their applicability for robust disease modeling and drug screening platforms for most common neurodegenerative conditions.
Topics: Animals; CRISPR-Cas Systems; Drug Evaluation, Preclinical; Gene Editing; Humans; Neurodegenerative Diseases; Neurogenesis; Neurons; Pluripotent Stem Cells
PubMed: 31161803
DOI: 10.4155/fmc-2018-0520 -
Current Stem Cell Research & Therapy 2021Liver disease (hepatic disease) adversely affects the normal function of the liver and causes liver problems. Drug-induced liver injury (DILI) can be predicted by... (Review)
Review
Liver disease (hepatic disease) adversely affects the normal function of the liver and causes liver problems. Drug-induced liver injury (DILI) can be predicted by primary human hepatocytes. However, the sources of hepatocytes for large-scale drug toxicity screening are limited. To solve this problem, pluripotent stem cells (PSCs), mesenchymal stem cells (MSCs), and hepatic stem cells (HSCs) have emerged as attractive cell sources for cell-based therapies. Human PSCs, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the ability to undergo self-renewal and differentiate into lineages of ectoderm, mesoderm, and endoderm. Human PSC can be used for the generation of hepatocytes to facilitate the development of novel drugs for the treatment of severe liver diseases. The therapeutic potential of PSC-derived hepatocytes for liver failure have been identified to enhance the development of chemically defined and xenogenic- free 3D culture methods. To date, several hepatic differentiation strategies and various extracellular matrix (ECM) components have been employed to produce hepatocytes or hepatic-like cells (HLCs) in vitro. In this review, we focused on the potential of Matrigel, collagen type 1, Ro- Gel, and laminin as ECM on the differentiation and function of hESC- and hiPSC-derived hepatocytes. The hepatic differentiation of human ESCs and iPSCs would offer an ideal tool for cell therapy and liver diseases.
Topics: Cell Culture Techniques; Cell Differentiation; Embryonic Stem Cells; Extracellular Matrix; Hepatocytes; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells
PubMed: 33371861
DOI: 10.2174/1574888X16666201228144834 -
Wiley Interdisciplinary Reviews.... May 2020Too many choices can be problematic. This is certainly the case for human pluripotent stem cells (hPSCs): they harbor the potential to differentiate into hundreds of... (Review)
Review
Too many choices can be problematic. This is certainly the case for human pluripotent stem cells (hPSCs): they harbor the potential to differentiate into hundreds of cell types; yet it is highly challenging to exclusively differentiate hPSCs into a single desired cell type. This review focuses on unresolved and fundamental questions regarding hPSC differentiation and critiquing the identity and purity of the resultant cell populations. These are timely issues in view of the fact that hPSC-derived cell populations have or are being transplanted into patients in over 30 ongoing clinical trials. While many in vitro differentiation protocols purport to "mimic development," the exact number and identity of intermediate steps that a pluripotent cell takes to differentiate into a given cell type in vivo remains largely unknown. Consequently, most differentiation efforts inevitably generate a heterogeneous cellular population, as revealed by single-cell RNA-sequencing and other analyses. The presence of unwanted cell types in differentiated hPSC populations does not portend well for transplantation therapies. This provides an impetus to precisely control differentiation to desired ends-for instance, by logically blocking the formation of unwanted cell types or by overexpressing lineage-specifying transcription factors-or by harnessing technologies to selectively purify desired cell types. Conversely, approaches to differentiate three-dimensional "organoids" from hPSCs intentionally generate heterogeneous cell populations. While this is intended to mimic the rich cellular diversity of developing tissues, whether all such organoids are spatially organized in a manner akin to native organs (and thus, whether they fully qualify as organoids) remains to be fully resolved. This article is categorized under: Adult Stem Cells > Tissue Renewal > Regeneration: Stem Cell Differentiation and Reversion Gene Expression > Transcriptional Hierarchies: Cellular Differentiation Early Embryonic Development: Gastrulation and Neurulation.
Topics: Cell Differentiation; Cellular Reprogramming Techniques; Humans; Organoids; Pluripotent Stem Cells; Primary Cell Culture
PubMed: 31746148
DOI: 10.1002/wdev.368 -
Theriogenology Nov 2012Pluripotent stem cells have the capacity to divide indefinitely and to differentiate into all somatic cells and tissue lines. They can be genetically manipulated in... (Review)
Review
Pluripotent stem cells have the capacity to divide indefinitely and to differentiate into all somatic cells and tissue lines. They can be genetically manipulated in vitro by knocking genes in or out, and therefore serve as an excellent tool for gene function studies and for the generation of models for some human diseases. Since 1981, when the first mouse embryonic stem cell (ESC) line was generated, many attempts have been made to generate pluripotent stem cell lines from other species. Comparative characterization of ESCs from different species would help us to understand differences and similarities in the signaling pathways involved in the maintenance of pluripotency and the initiation of differentiation, and would reveal whether the fundamental mechanism controlling self-renewal of pluripotent cells is conserved across different species. This report gives an overview of research into embryonic and induced pluripotent stem cells in the rabbit, an important nonrodent species with considerable merits as an animal model for specific diseases. A number of putative rabbit ESC and induced pluripotent stem cell lines have been described. All of them expressed stem cell-associated markers and maintained apparent pluripotency during multiple passages in vitro, but none have been convincingly proven to be fully pluripotent in vivo. Moreover, as in other domestic species, the markers currently used to characterize the putative rabbit ESCs are suboptimal because recent studies have revealed that they are not always specific to the pluripotent inner cell mass. Future validation of rabbit pluripotent stem cells would benefit greatly from a validated panel of molecular markers specific to pluripotent cells of the developing rabbit embryos. Using rabbit-specific pluripotency genes may improve the efficiency of somatic cell reprogramming for generating induced pluripotent stem cells and thereby overcome some of the challenges limiting the potential of this technology.
Topics: Animals; Cell Differentiation; Cell Line; Chimera; Embryonic Stem Cells; Immunohistochemistry; Induced Pluripotent Stem Cells; MicroRNAs; Models, Animal; Nuclear Transfer Techniques; Pluripotent Stem Cells; Rabbits; Transcription Factors
PubMed: 22925641
DOI: 10.1016/j.theriogenology.2012.06.017 -
Methods in Molecular Biology (Clifton,... 2022In this chapter, an efficient feeder-free protocol of differentiating human pluripotent stem cells (hPSCs) toward the epidermal lineage to generate induced epidermal...
In this chapter, an efficient feeder-free protocol of differentiating human pluripotent stem cells (hPSCs) toward the epidermal lineage to generate induced epidermal keratinocytes (iKCs) is described. The iKCs are able to terminally differentiate supra-basally. This hPSC-to-iKC differentiation can serve as a useful model to study epidermal development and disease as well as for therapeutic applications.
Topics: Cell Differentiation; Cell Line; Epithelial Cells; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells
PubMed: 32833130
DOI: 10.1007/7651_2020_301 -
Current Topics in Developmental Biology 2013Embryonic stem cells (ESCs) can self renew and retain the potential to differentiate into each of the cell types within the body. During experimental reprogramming, many... (Review)
Review
Embryonic stem cells (ESCs) can self renew and retain the potential to differentiate into each of the cell types within the body. During experimental reprogramming, many of the features of ESCs can be acquired by differentiated target cells. One of these is the unusual cell division cycle that characterizes ESCs in which the Gap (G) phases are short and DNA Synthesis (S) phase predominates. Growing evidence has suggested that this atypical cell-cycle structure may be important for maintaining pluripotency and for enhancing pluripotent conversion. Here, we review current knowledge of cell-cycle regulation in ESCs and outline how this unique cell-cycle structure might contribute to successful reprogramming.
Topics: Animals; Cell Cycle; Cellular Reprogramming; Chromatin Assembly and Disassembly; DNA; Epigenesis, Genetic; Humans; Pluripotent Stem Cells
PubMed: 23587243
DOI: 10.1016/B978-0-12-416027-9.00007-3 -
Cell Stem Cell Jan 2014Human pluripotent stem cells (hPSCs) provide powerful resources for application in regenerative medicine and pharmaceutical development. In the past decade, various... (Review)
Review
Human pluripotent stem cells (hPSCs) provide powerful resources for application in regenerative medicine and pharmaceutical development. In the past decade, various methods have been developed for large-scale hPSC culture that rely on combined use of multiple growth components, including media containing various growth factors, extracellular matrices, 3D environmental cues, and modes of multicellular association. In this Protocol Review, we dissect these growth components by comparing cell culture methods and identifying the benefits and pitfalls associated with each one. We further provide criteria, considerations, and suggestions to achieve optimal cell growth for hPSC expansion, differentiation, and use in future therapeutic applications.
Topics: Cell Culture Techniques; Cell Differentiation; Humans; Pluripotent Stem Cells
PubMed: 24388173
DOI: 10.1016/j.stem.2013.12.005 -
Trends in Cell Biology Dec 2018The ability to shift between metabolic states and to tightly regulate cellular mechanical properties have been described as crucial events in the achievement of correct... (Review)
Review
The ability to shift between metabolic states and to tightly regulate cellular mechanical properties have been described as crucial events in the achievement of correct embryonic development. Indeed, metabolic and mechanical manipulations in vitro have led to the discovery of new methods to control cell fate. As these two modulators are usually studied separately, in this review article, we describe how cellular mechanics and metabolic characteristics regulate embryonic development in vivo and describe the role of these cues in the regulation of pluripotency and differentiation in vitro. We also pinpoint possible connections between metabolism and mechanotransduction, highlighting recent findings in the Yes-associated protein, phosphoinositide 3-kinase, and AMP-activated protein kinase signaling pathways, and how they may be relevant in modulating cell fate in other contexts.
Topics: Animals; Biomechanical Phenomena; Cell Differentiation; Humans; Pluripotent Stem Cells
PubMed: 30361056
DOI: 10.1016/j.tcb.2018.09.005 -
Journal of Biomedicine & Biotechnology 2011Although there are a number of weaknesses for clinical use, pluripotent stem cells are valuable sources for patient-specific cell therapies against various diseases.... (Review)
Review
Although there are a number of weaknesses for clinical use, pluripotent stem cells are valuable sources for patient-specific cell therapies against various diseases. Backed-up by a huge number of basic researches, neuronal differentiation mechanism is well established and pluripotent stem cell therapies against neurological disorders are getting closer to clinical application. However, there are increasing needs for standardization of the sourcing pluripotent stem cells by establishing stem cell registries and banking. Global harmonization will accelerate practical use of personalized therapies using pluripotent stem cells.
Topics: Cell Differentiation; Cell- and Tissue-Based Therapy; Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Nervous System Diseases; Pluripotent Stem Cells; Stem Cell Transplantation
PubMed: 22203784
DOI: 10.1155/2011/520816 -
The Journal of Biological Chemistry Feb 2014Induced pluripotent stem cells (iPSCs) and their differentiated derivatives can potentially be applied to cell-based therapy for human diseases. The properties of iPSCs... (Review)
Review
Induced pluripotent stem cells (iPSCs) and their differentiated derivatives can potentially be applied to cell-based therapy for human diseases. The properties of iPSCs are being studied intensively both to understand the basic biology of pluripotency and cellular differentiation and to solve problems associated with therapeutic applications. Examples of specific preclinical applications summarized briefly in this minireview include the use of iPSCs to treat diseases of the liver, nervous system, eye, and heart and metabolic conditions such as diabetes. Early stage studies illustrate the potential of iPSC-derived cells and have identified several challenges that must be addressed before moving to clinical trials. These include rigorous quality control and efficient production of required cell populations, improvement of cell survival and engraftment, and development of technologies to monitor transplanted cell behavior for extended periods of time. Problems related to immune rejection, genetic instability, and tumorigenicity must be solved. Testing the efficacy of iPSC-based therapies requires further improvement of animal models precisely recapitulating human disease conditions.
Topics: Animals; Disease Models, Animal; Humans; Induced Pluripotent Stem Cells; Stem Cell Transplantation
PubMed: 24362021
DOI: 10.1074/jbc.R113.463737