-
International Journal of Molecular... May 2021Stem cell research is essential not only for the research and treatment of human diseases, but also for the genetic preservation and improvement of animals. Since... (Review)
Review
Stem cell research is essential not only for the research and treatment of human diseases, but also for the genetic preservation and improvement of animals. Since embryonic stem cells (ESCs) were established in mice, substantial efforts have been made to establish true ESCs in many species. Although various culture conditions were used to establish ESCs in cattle, the capturing of true bovine ESCs (bESCs) has not been achieved. In this review, the difficulty of establishing bESCs with various culture conditions is described, and the characteristics of proprietary induced pluripotent stem cells and extended pluripotent stem cells are introduced. We conclude with a suggestion of a strategy for establishing true bESCs.
Topics: Animals; Biomarkers; Cattle; Cell Culture Techniques; Cell Differentiation; Cell- and Tissue-Based Therapy; Cells, Cultured; Cellular Reprogramming; Cellular Reprogramming Techniques; Embryonic Stem Cells; Genetic Engineering; Immunophenotyping; Induced Pluripotent Stem Cells; Pluripotent Stem Cells
PubMed: 34065074
DOI: 10.3390/ijms22095011 -
International Journal of Molecular... Jul 2021The blood-brain barrier (BBB) regulates the delivery of oxygen and important nutrients to the brain through active and passive transport and prevents neurotoxins from... (Review)
Review
The blood-brain barrier (BBB) regulates the delivery of oxygen and important nutrients to the brain through active and passive transport and prevents neurotoxins from entering the brain. It also has a clearance function and removes carbon dioxide and toxic metabolites from the central nervous system (CNS). Several drugs are unable to cross the BBB and enter the CNS, adding complexity to drug screens targeting brain disorders. A well-functioning BBB is essential for maintaining healthy brain tissue, and a malfunction of the BBB, linked to its permeability, results in toxins and immune cells entering the CNS. This impairment is associated with a variety of neurological diseases, including Alzheimer's disease and Parkinson's disease. Here, we summarize current knowledge about the BBB in neurodegenerative diseases. Furthermore, we focus on recent progress of using human-induced pluripotent stem cell (iPSC)-derived models to study the BBB. We review the potential of novel stem cell-based platforms in modeling the BBB and address advances and key challenges of using stem cell technology in modeling the human BBB. Finally, we highlight future directions in this area.
Topics: Animals; Blood-Brain Barrier; Brain; Cerebrovascular Circulation; Humans; Induced Pluripotent Stem Cells; Models, Biological; Neurodegenerative Diseases
PubMed: 34299328
DOI: 10.3390/ijms22147710 -
Stem Cell Reports Jun 2017Embryonic stem cells (ESCs) are a unique tool for genetic perturbation of mammalian cellular and organismal processes additionally in humans offer unprecedented... (Review)
Review
Embryonic stem cells (ESCs) are a unique tool for genetic perturbation of mammalian cellular and organismal processes additionally in humans offer unprecedented opportunities for disease modeling and cell therapy. Furthermore, ESCs are a powerful system for exploring the fundamental biology of pluripotency. Indeed understanding the control of self-renewal and differentiation is key to realizing the potential of ESCs. Building on previous observations, we found that mouse ESCs can be derived and maintained with high efficiency through insulation from differentiation cues combined with consolidation of an innate cell proliferation program. This finding of a pluripotent ground state has led to conceptual and practical advances, including the establishment of germline-competent ESCs from recalcitrant mouse strains and for the first time from the rat. Here, we summarize historical and recent progress in defining the signaling environment that supports self-renewal. We compare the contrasting requirements of two types of pluripotent stem cell, naive ESCs and primed post-implantation epiblast stem cells (EpiSCs), and consider the outstanding challenge of generating naive pluripotent stem cells from different mammals.
Topics: Animals; Cell Differentiation; Cell Self Renewal; Embryonic Stem Cells; Glycogen Synthase Kinase 3; Humans; Leukemia Inhibitory Factor; Pluripotent Stem Cells; Signal Transduction; Transcription Factors
PubMed: 28591647
DOI: 10.1016/j.stemcr.2017.05.020 -
BMC Developmental Biology Jun 2017Pluripotency defines the propensity of a cell to differentiate into, and generate, all somatic, as well as germ cells. The epiblast of the early mammalian embryo is the... (Review)
Review
Pluripotency defines the propensity of a cell to differentiate into, and generate, all somatic, as well as germ cells. The epiblast of the early mammalian embryo is the founder population of all germ layer derivatives and thus represents the bona fide in vivo pluripotent cell population. The so-called pluripotent state spans several days of development and is lost during gastrulation as epiblast cells make fate decisions towards a mesoderm, endoderm or ectoderm identity. It is now widely recognized that the features of the pluripotent population evolve as development proceeds from the pre- to post-implantation period, marked by distinct transcriptional and epigenetic signatures. During this period of time epiblast cells mature through a continuum of pluripotent states with unique properties. Aspects of this pluripotent continuum can be captured in vitro in the form of stable pluripotent stem cell types. In this review we discuss the continuum of pluripotency existing within the mammalian embryo, using the mouse as a model, and the cognate stem cell types that can be derived and propagated in vitro. Furthermore, we speculate on embryonic stage-specific characteristics that could be utilized to identify novel, developmentally relevant, pluripotent states.
Topics: Animals; Blastocyst; Cell Differentiation; Gastrulation; Germ Layers; Pluripotent Stem Cells; Signal Transduction
PubMed: 28610558
DOI: 10.1186/s12861-017-0150-4 -
Journal of Biomedical Science Apr 2021A brain organoid is a self-organizing three-dimensional tissue derived from human embryonic stem cells or pluripotent stem cells and is able to simulate the architecture... (Review)
Review
A brain organoid is a self-organizing three-dimensional tissue derived from human embryonic stem cells or pluripotent stem cells and is able to simulate the architecture and functionality of the human brain. Brain organoid generation methods are abundant and continue to improve, and now, an in vivo vascularized brain organoid has been encouragingly reported. The combination of brain organoids with immune-staining and single-cell sequencing technology facilitates our understanding of brain organoids, including the structural organization and the diversity of cell types. Recent publications have reported that brain organoids can mimic the dynamic spatiotemporal process of early brain development, model various human brain disorders, and serve as an effective preclinical platform to test and guide personalized treatment. In this review, we introduce the current state of brain organoid differentiation strategies, summarize current progress and applications in the medical domain, and discuss the challenges and prospects of this promising technology.
Topics: Brain; Cell Differentiation; Embryonic Stem Cells; Humans; Organoids; Pluripotent Stem Cells
PubMed: 33888112
DOI: 10.1186/s12929-021-00728-4 -
Protein & Cell Jun 2021Dedifferentiation of cell identity to a progenitor-like or stem cell-like state with increased cellular plasticity is frequently observed in cancer formation. During... (Review)
Review
Dedifferentiation of cell identity to a progenitor-like or stem cell-like state with increased cellular plasticity is frequently observed in cancer formation. During this process, a subpopulation of cells in tumours acquires a stem cell-like state partially resembling to naturally occurring pluripotent stem cells that are temporarily present during early embryogenesis. Such characteristics allow these cancer stem cells (CSCs) to give rise to the whole tumour with its entire cellular heterogeneity and thereby support metastases formation while being resistant to current cancer therapeutics. Cancer development and progression are demarcated by transcriptional dysregulation. In this article, we explore the epigenetic mechanisms shaping gene expression during tumorigenesis and cancer stem cell formation, with an emphasis on 3D chromatin architecture. Comparing the pluripotent stem cell state and epigenetic reprogramming to dedifferentiation in cellular transformation provides intriguing insight to chromatin dynamics. We suggest that the 3D chromatin architecture could be used as a target for re-sensitizing cancer stem cells to therapeutics.
Topics: Animals; Carcinogenesis; Cellular Reprogramming; Chromatin; Chromatin Assembly and Disassembly; Epigenesis, Genetic; Humans; Neoplasms; Neoplastic Stem Cells; Pluripotent Stem Cells
PubMed: 33453053
DOI: 10.1007/s13238-020-00819-2 -
Cells Apr 2024The human respiratory system is susceptible to a variety of diseases, ranging from chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis to acute... (Review)
Review
The human respiratory system is susceptible to a variety of diseases, ranging from chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis to acute respiratory distress syndrome (ARDS). Today, lung diseases represent one of the major challenges to the health care sector and represent one of the leading causes of death worldwide. Current treatment options often focus on managing symptoms rather than addressing the underlying cause of the disease. The limitations of conventional therapies highlight the urgent clinical need for innovative solutions capable of repairing damaged lung tissue at a fundamental level. Pluripotent stem cell technologies have now reached clinical maturity and hold immense potential to revolutionize the landscape of lung repair and regenerative medicine. Meanwhile, human embryonic (HESCs) and human-induced pluripotent stem cells (hiPSCs) can be coaxed to differentiate into lung-specific cell types such as bronchial and alveolar epithelial cells, or pulmonary endothelial cells. This holds the promise of regenerating damaged lung tissue and restoring normal respiratory function. While methods for targeted genetic engineering of hPSCs and lung cell differentiation have substantially advanced, the required GMP-grade clinical-scale production technologies as well as the development of suitable preclinical animal models and cell application strategies are less advanced. This review provides an overview of current perspectives on PSC-based therapies for lung repair, explores key advances, and envisions future directions in this dynamic field.
Topics: Animals; Humans; Endothelial Cells; Pluripotent Stem Cells; Induced Pluripotent Stem Cells; Lung; Pulmonary Fibrosis
PubMed: 38607074
DOI: 10.3390/cells13070635 -
Experimental Cell Research Apr 2020Both embryo-derived (ESC) and induced pluripotent stem cell (iPSC) lines have been established in rabbit. They exhibit the essential characteristics of primed... (Review)
Review
Both embryo-derived (ESC) and induced pluripotent stem cell (iPSC) lines have been established in rabbit. They exhibit the essential characteristics of primed pluripotency. In this review, we described their characteristic features at both molecular and functional levels. We also described the attempts to reprogram rabbit pluripotent stem cells (rbPSCs) toward the naive state of pluripotency using methods established previously to capture this state in rodents and primates. In the last section, we described and discussed our current knowledge of rabbit embryo development pertaining to the mechanisms of early lineage segregation. We argued that the molecular signature of naive-state pluripotency differs between mice and rabbits. We finally discussed some of the key issues to be addressed for capturing the naive state in rbPSCs, including the generation of embryo/PSC chimeras.
Topics: Animals; Cell Differentiation; Chimera; Embryo, Mammalian; Embryonic Development; Embryonic Stem Cells; Gene Expression Regulation, Developmental; Induced Pluripotent Stem Cells; Rabbits
PubMed: 32057751
DOI: 10.1016/j.yexcr.2020.111908 -
Acta Biochimica Et Biophysica Sinica Jul 2020Diabetes mellitus is characterized by chronic high blood glucose levels resulted from deficiency and/or dysfunction of insulin-producing pancreatic β cells. Generation... (Review)
Review
Diabetes mellitus is characterized by chronic high blood glucose levels resulted from deficiency and/or dysfunction of insulin-producing pancreatic β cells. Generation of large amounts of functional pancreatic β cells is critical for the study of pancreatic biology and treatment of diabetes. Recent advances in directed differentiation of pancreatic β-like cells from human pluripotent stem cells (hPSCs) can provide patient-specific and disease-relevant target cells. With the improved differentiation protocols, it is now possible to generate large amounts of functional human pancreatic β-like cells that can response to high level of glucose both in vitro and in vivo. Combined with precise genomic editing, biomedical engineering, high throughput profiling, bioinformatics, and high throughput genetic and chemical screening, these hPSC-derived pancreatic β-like cells will hold great potentials in disease modeling, drug discovery, and cell-based therapies. In this review, we summarize the recent progress in human pancreatic β-like cells derived from hPSCs and discuss their potential applications.
Topics: Animals; Cell Differentiation; Diabetes Mellitus; Gene Editing; Humans; Insulin-Secreting Cells; Models, Biological; Pluripotent Stem Cells
PubMed: 32445468
DOI: 10.1093/abbs/gmaa047 -
Molecules and Cells Mar 2019Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been used as promising tools for regenerative medicine, disease modeling, and drug screening.... (Review)
Review
Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been used as promising tools for regenerative medicine, disease modeling, and drug screening. Traditional and common strategies for pluripotent stem cell (PSC) differentiation toward disease-relevant cell types depend on sequential treatment of signaling molecules identified based on knowledge of developmental biology. However, these strategies suffer from low purity, inefficiency, and time-consuming culture conditions. A growing body of recent research has shown efficient cell fate reprogramming by forced expression of single or multiple transcription factors. Here, we review transcription factor-directed differentiation methods of PSCs toward neural, muscle, liver, and pancreatic endocrine cells. Potential applications and limitations are also discussed in order to establish future directions of this technique for therapeutic purposes.
Topics: Animals; Cell Differentiation; Hepatocytes; Humans; Insulin-Secreting Cells; Neurons; Pluripotent Stem Cells; Transcription Factors
PubMed: 30884942
DOI: 10.14348/molcells.2019.2439