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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 -
Nature Cell Biology Sep 2019Cyclins, cyclin-dependent kinases and other components of the core cell cycle machinery drive cell division. Growing evidence indicates that this machinery operates in a... (Review)
Review
Cyclins, cyclin-dependent kinases and other components of the core cell cycle machinery drive cell division. Growing evidence indicates that this machinery operates in a distinct fashion in some mammalian stem cell types, such as pluripotent embryonic stem cells. In this Review, we discuss our current knowledge of how cell cycle proteins mechanistically link cell proliferation, pluripotency and cell fate specification. We focus on embryonic stem cells, induced pluripotent stem cells and embryonic neural stem/progenitor cells.
Topics: Animals; Cell Cycle; Cell Differentiation; Cell Proliferation; Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells
PubMed: 31481793
DOI: 10.1038/s41556-019-0384-4 -
Cell May 2021Since establishment of the first embryonic stem cells (ESCs), in vitro culture of totipotent cells functionally and molecularly comparable with in vivo blastomeres...
Since establishment of the first embryonic stem cells (ESCs), in vitro culture of totipotent cells functionally and molecularly comparable with in vivo blastomeres with embryonic and extraembryonic developmental potential has been a challenge. Here we report that spliceosomal repression in mouse ESCs drives a pluripotent-to-totipotent state transition. Using the splicing inhibitor pladienolide B, we achieve stable in vitro culture of totipotent ESCs comparable at molecular levels with 2- and 4-cell blastomeres, which we call totipotent blastomere-like cells (TBLCs). Mouse chimeric assays combined with single-cell RNA sequencing (scRNA-seq) demonstrate that TBLCs have a robust bidirectional developmental capability to generate multiple embryonic and extraembryonic cell lineages. Mechanically, spliceosomal repression causes widespread splicing inhibition of pluripotent genes, whereas totipotent genes, which contain few short introns, are efficiently spliced and transcriptionally activated. Our study provides a means for capturing and maintaining totipotent stem cells.
Topics: Animals; Blastomeres; Cell Differentiation; Cell Line; Cell Lineage; Embryo, Mammalian; Embryonic Stem Cells; Female; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Mouse Embryonic Stem Cells; Totipotent Stem Cells
PubMed: 33991488
DOI: 10.1016/j.cell.2021.04.020 -
International Journal of Molecular... Feb 2020Adipose tissue derived stem cells (ADSCs) are mesenchymal stem cells identified within subcutaneous tissue at the base of the hair follicle (dermal papilla cells), in... (Review)
Review
Adipose tissue derived stem cells (ADSCs) are mesenchymal stem cells identified within subcutaneous tissue at the base of the hair follicle (dermal papilla cells), in the dermal sheets (dermal sheet cells), in interfollicular dermis, and in the hypodermis tissue. These cells are expected to play a major role in regulating skin regeneration and aging-associated morphologic disgraces and structural deficits. ADSCs are known to proliferate and differentiate into skin cells to repair damaged or dead cells, but also act by an autocrine and paracrine pathway to activate cell regeneration and the healing process. During wound healing, ADSCs have a great ability in migration to be recruited rapidly into wounded sites added to their differentiation towards dermal fibroblasts (DF), endothelial cells, and keratinocytes. Additionally, ADSCs and DFs are the major sources of the extracellular matrix (ECM) proteins involved in maintaining skin structure and function. Their interactions with skin cells are involved in regulating skin homeostasis and during healing. The evidence suggests that their secretomes ensure: (i) The change in macrophages inflammatory phenotype implicated in the inflammatory phase, (ii) the formation of new blood vessels, thus promoting angiogenesis by increasing endothelial cell differentiation and cell migration, and (iii) the formation of granulation tissues, skin cells, and ECM production, whereby proliferation and remodeling phases occur. These characteristics would be beneficial to therapeutic strategies in wound healing and skin aging and have driven more insights in many clinical investigations. Additionally, it was recently presented as the tool key in the new free-cell therapy in regenerative medicine. Nevertheless, ADSCs fulfill the general accepted criteria for cell-based therapies, but still need further investigations into their efficiency, taking into consideration the host-environment and patient-associated factors.
Topics: Adipose Tissue; Cell- and Tissue-Based Therapy; Humans; Mesenchymal Stem Cells; Regenerative Medicine; Skin Aging; Skin Diseases; Stem Cell Transplantation; Stem Cells; Wound Healing
PubMed: 32075181
DOI: 10.3390/ijms21041306 -
Signal Transduction and Targeted Therapy Jan 2024Although stem cell-based therapy has demonstrated considerable potential to manage certain diseases more successfully than conventional surgery, it nevertheless comes... (Review)
Review
Although stem cell-based therapy has demonstrated considerable potential to manage certain diseases more successfully than conventional surgery, it nevertheless comes with inescapable drawbacks that might limit its clinical translation. Compared to stem cells, stem cell-derived exosomes possess numerous advantages, such as non-immunogenicity, non-infusion toxicity, easy access, effortless preservation, and freedom from tumorigenic potential and ethical issues. Exosomes can inherit similar therapeutic effects from their parental cells such as embryonic stem cells and adult stem cells through vertical delivery of their pluripotency or multipotency. After a thorough search and meticulous dissection of relevant literature from the last five years, we present this comprehensive, up-to-date, specialty-specific and disease-oriented review to highlight the surgical application and potential of stem cell-derived exosomes. Exosomes derived from stem cells (e.g., embryonic, induced pluripotent, hematopoietic, mesenchymal, neural, and endothelial stem cells) are capable of treating numerous diseases encountered in orthopedic surgery, neurosurgery, plastic surgery, general surgery, cardiothoracic surgery, urology, head and neck surgery, ophthalmology, and obstetrics and gynecology. The diverse therapeutic effects of stem cells-derived exosomes are a hierarchical translation through tissue-specific responses, and cell-specific molecular signaling pathways. In this review, we highlight stem cell-derived exosomes as a viable and potent alternative to stem cell-based therapy in managing various surgical conditions. We recommend that future research combines wisdoms from surgeons, nanomedicine practitioners, and stem cell researchers in this relevant and intriguing research area.
Topics: Exosomes; Mesenchymal Stem Cells; Induced Pluripotent Stem Cells; Embryonic Stem Cells
PubMed: 38212307
DOI: 10.1038/s41392-023-01704-0 -
Cells Mar 2021The main difficulty of radiotherapy is to destroy cancer cells without depletion of healthy tissue [...].
The main difficulty of radiotherapy is to destroy cancer cells without depletion of healthy tissue [...].
Topics: Adult Stem Cells; Cell- and Tissue-Based Therapy; Homeostasis; Humans; Neoplastic Stem Cells; Organoids; Radiation; Stem Cells
PubMed: 33808269
DOI: 10.3390/cells10040760 -
Cell Reports Oct 2022Stem cells play central roles in tissue development, homeostasis, and regeneration. Decades of scientific research have uncovered processes of stem cell decline in... (Review)
Review
Stem cells play central roles in tissue development, homeostasis, and regeneration. Decades of scientific research have uncovered processes of stem cell decline in tissue and organismal aging, and more recently, pioneering technologies permit the dissection of its underlying mechanisms and inform therapeutic development for aging and aging-associated disorders. In this review, we elucidate aging-related features across different somatic stem cell types, with a specific focus on epigenetic changes, loss of protein homeostasis, and systemic influencing factors, including chronic inflammation, circadian rhythm dysregulation, and metabolic disorder. Our survey of organismal stem cell aging summarizes its underlying biological implications, points to potential biomarkers of stem cell aging, and discusses stem cell-based therapeutic strategies with the potential for promoting healthy aging and combating aging and age-related diseases.
Topics: Cellular Senescence; Stem Cells; Proteostasis; Adult Stem Cells
PubMed: 36261013
DOI: 10.1016/j.celrep.2022.111451 -
Neuron Dec 2019Neural stem cells in the adult mammalian brain are the source of new neurons that contribute to complex sensory and cognitive functions. Most adult neural stem cells are... (Review)
Review
Neural stem cells in the adult mammalian brain are the source of new neurons that contribute to complex sensory and cognitive functions. Most adult neural stem cells are maintained in a state of reversible cell cycle arrest, also called quiescence. Quiescent neural stem cells present a low rate of metabolic activity and a high sensitivity to their local signaling environment, and they can be activated by diverse physiological stimuli. The balance between stem cell quiescence and activity determines not only the rate of neurogenesis but also the long-term maintenance of the stem cell pool and the neurogenic capacity of the aging brain. In recent years, significant progress has been made in characterizing quiescent stem cells thanks to the introduction of new genomic and imaging techniques. We discuss in this review our current understanding of neural stem cell quiescence and its regulation by intrinsic and systemic factors.
Topics: Adult Stem Cells; Animals; Humans; Neural Stem Cells; Neurogenesis
PubMed: 31805262
DOI: 10.1016/j.neuron.2019.09.026 -
Stem Cell Research & Therapy Aug 2019The injured spinal cord is difficult to repair and regenerate. Traditional treatments are not effective. Stem cells are a type of cells that have the potential to... (Review)
Review
The injured spinal cord is difficult to repair and regenerate. Traditional treatments are not effective. Stem cells are a type of cells that have the potential to differentiate into various cells, including neurons. They exert a therapeutic effect by safely and effectively differentiating into neurons or replacing damaged cells, secreting neurotrophic factors, and inhibiting the inflammatory response. Many types of stem cells have been used for transplantation, and each has its own advantages and disadvantages. This review discusses the possible mechanisms of stem cell therapy for spinal cord injury, and the types of stem cells commonly used in experiments, to provide a reference for basic and clinical research on stem cell therapy for spinal cord injury.
Topics: Animals; Cell- and Tissue-Based Therapy; Embryonic Stem Cells; Induced Pluripotent Stem Cells; Mesenchymal Stem Cells; Nerve Regeneration; Neural Stem Cells; Spinal Cord Injuries; Stem Cell Transplantation; Stem Cells
PubMed: 31387621
DOI: 10.1186/s13287-019-1357-z -
Cell Stem Cell Sep 2022Quiescence regulation is essential for adult stem cell maintenance and sustained regeneration. Our studies uncovered that physiological changes in mitochondrial shape...
Quiescence regulation is essential for adult stem cell maintenance and sustained regeneration. Our studies uncovered that physiological changes in mitochondrial shape regulate the quiescent state of adult muscle stem cells (MuSCs). We show that MuSC mitochondria rapidly fragment upon an activation stimulus, via systemic HGF/mTOR, to drive the exit from deep quiescence. Deletion of the mitochondrial fusion protein OPA1 and mitochondrial fragmentation transitions MuSCs into G-alert quiescence, causing premature activation and depletion upon a stimulus. OPA1 loss activates a glutathione (GSH)-redox signaling pathway promoting cell-cycle progression, myogenic gene expression, and commitment. MuSCs with chronic OPA1 loss, leading to mitochondrial dysfunction, continue to reside in G-alert but acquire severe cell-cycle defects. Additionally, we provide evidence that OPA1 decline and impaired mitochondrial dynamics contribute to age-related MuSC dysfunction. These findings reveal a fundamental role for OPA1 and mitochondrial dynamics in establishing the quiescent state and activation potential of adult stem cells.
Topics: Adult Stem Cells; Mitochondrial Dynamics; Mitochondrial Proteins; Muscles; Myoblasts
PubMed: 35998642
DOI: 10.1016/j.stem.2022.07.010