scholarly journals Mitochondrial Dynamics: Biogenesis, Fission, Fusion, and Mitophagy in the Regulation of Stem Cell Behaviors

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Wenyan Fu ◽  
Yang Liu ◽  
Hang Yin
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Therapeutic Potential ◽  
Mitochondrial Dynamics ◽  
Research Progress ◽  
Extrinsic Factors ◽  
Self Renewal ◽  
Cell Behaviors ◽  
Cell Based Therapy ◽  
Proliferation And Differentiation

Stem cells have the unique capacity to differentiate into many cell types during embryonic development and postnatal growth. Through coordinated cellular behaviors (self-renewal, proliferation, and differentiation), stem cells are also pivotal to the homeostasis, repair, and regeneration of many adult tissues/organs and thus of great importance in regenerative medicine. Emerging evidence indicates that mitochondria are actively involved in the regulation of stem cell behaviors. Mitochondria undergo specific dynamics (biogenesis, fission, fusion, and mitophagy) during stem cell self-renewal, proliferation, and differentiation. The alteration of mitochondrial dynamics, fine-tuned by stem cell niche factors and stress signaling, has considerable impacts on stem cell behaviors. Here, we summarize the recent research progress on (1) how mitochondrial dynamics controls stem cell behaviors, (2) intrinsic and extrinsic factors that regulate mitochondrial dynamics, and (3) pharmacological regulators of mitochondrial dynamics and their therapeutic potential. This review emphasizes the metabolic control of stemness and differentiation and may shed light on potential new applications in stem cell-based therapy.

scholarly journals Effect of Astragaloside IV on Neural Stem Cell Transplantation in Alzheimer’s Disease Rat Models

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Hu Haiyan ◽  
Yang Rensong ◽  
Jin Guoqin ◽  
Zhang Xueli ◽  
Xia Huaying ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Stem Cell ◽  
Learning And Memory ◽  
High Dose ◽  
Astragaloside Iv ◽  
Cell Based Therapy ◽  
Proliferation And Differentiation

Stem cell-based therapy is a promising treatment strategy for neurodegenerative diseases such as Alzheimer’s disease (AD). However, the mechanism underlying the maintenance of renewal and replacement capabilities of endogenous progenitor cells or engrafted stem cells in a pathological environment remains elusive. To investigate the effect of astragaloside IV (ASI) on the proliferation and differentiation of the engrafted neural stem cells (NSCs), we cultured NSCs from the hippocampus of E14 rat embryos, treated the cells with ASI, and then transplanted the cells into the hippocampus of rat AD models.In vitroexperimentation showed that 10−5 M ASI induced NSCs to differentiate intoβ-tubulin III+and GFAP+cells. NSCs transplantation into rat AD models resulted in improvements in learning and memory, especially in the ASI-treated groups. ASI treatment resulted in an increase in the number ofβ-tubulin III+cells in the hippocampus. Further investigation showed that ASI inhibited PS1 expressionin vitroandin vivo. The high-dose ASI downregulated the Notch intracellular domain, whereas the low-dose ASI increased Notch-1 and NICD. In conclusion, ASI treatment resulted in improvements in learning and memory of AD models by promoting NSC proliferation and differentiation partly through the Notch signal pathway.

scholarly journals Dynamic heterogeneity as a strategy of stem cell self-renewal

2016 ◽  
Vol 113 (27) ◽  
pp. 7509-7514 ◽  
Author(s):  
Philip Greulich ◽  
Benjamin D. Simons
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Lineage Tracing ◽  
Stem Cell Population ◽  
Dynamic Heterogeneity ◽  
Self Renewal ◽  
Proliferation And Differentiation ◽  
Epithelial Layers ◽  
Viable Mechanism ◽  
Reversible Transfer

To maintain cycling adult tissue in homeostasis the balance between proliferation and differentiation of stem cells needs to be precisely regulated. To investigate how stem cells achieve perfect self-renewal, emphasis has been placed on models in which stem cells progress sequentially through a one-way proliferative hierarchy. However, investigations of tissue regeneration have revealed a surprising degree of flexibility, with cells normally committed to differentiation able to recover stem cell competence following injury. Here, we investigate whether the reversible transfer of cells between states poised for proliferation or differentiation may provide a viable mechanism for a heterogeneous stem cell population to maintain homeostasis even under normal physiological conditions. By addressing the clonal dynamics, we show that such models of “dynamic heterogeneity” may be equally capable of describing the results of recent lineage tracing assays involving epithelial tissues. Moreover, together with competition for limited niche access, such models may provide a mechanism to render tissue homeostasis robust. In particular, in 2D epithelial layers, we show that the mechanism of dynamic heterogeneity avoids some pathological dependencies that undermine models based on a hierarchical stem/progenitor organization.

scholarly journals Identification of small juvenile stem cells in aged bone marrow and their therapeutic potential for repair of the ischemic heart

2013 ◽  
Vol 305 (9) ◽  
pp. H1354-H1362 ◽  
Author(s):  
Koichi Igura ◽  
Motoi Okada ◽  
Ha Won Kim ◽  
Muhammad Ashraf
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Therapeutic Potential ◽  
Left Ventricular ◽  
Stem Cell Markers ◽  
Differentiation Potential ◽  
Small Juvenile ◽  
Cardiomyogenic Differentiation ◽  
Proliferation And Differentiation

Stem cell-mediated cardiac regeneration is impaired with age. In this study, we identified a novel subpopulation of small juvenile stem cells (SJSCs) isolated from aged bone marrow-derived stem cells (BMSCs) with high proliferation and differentiation potential. SJSCs expressed mesenchymal stem cell markers, CD29+/CD44+/CD59+/CD90+, but were negative for CD45−/CD117− as examined by flow cytometry analysis. SJSCs showed higher proliferation, colony formation, and differentiation abilities compared with BMSCs. We also observed that SJSCs significantly expressed cardiac lineage markers (Gata-4 and myocyte-specific enhancer factor 2C) and pluripotency markers (octamer-binding transcription factor 4, sex-determining region Y box 2, stage-specific embryonic antigen 1, and Nanog) as well as antiaging factors such as telomerase reverse transcriptase and sirtuin 1. Interestingly, SJSCs either from young or aged animals showed significantly longer telomere length as well as lower senescence-associated β-galactosidase expression, suggesting that SJSCs possess antiaging properties, whereas aged BMSCs have limited potential for proliferation and differentiation. Furthermore, transplantation of aged SJSCs into the infarcted rat heart significantly reduced the infarction size and improved left ventricular function, whereas transplantation of aged BMSCs was less effective. Moreover, neovascularization as well as cardiomyogenic differentiation in the peri-infarcted area were significantly increased in the SJSC-transplanted group compared with the BMSC-transplated group, as evaluated by immunohistochemical analysis. Taken together, these findings demonstrate that SJSCs possess characteristics of antiaging, pluripotency, and high proliferation and differentiation rates, and, therefore, these cells offer great therapeutic potential for repair of the injured myocardium.

scholarly journals Circular RNAs in Stem Cells: from Basic Research to Clinical Implications

2021 ◽  
Author(s):  
Hui-Juan Lu ◽  
Juan Li ◽  
Guodong Yang ◽  
Cun-Jian Yi ◽  
Daping Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Basic Research ◽  
Cell Types ◽  
Circular Rnas ◽  
Diagnostic Significance ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Cell Based Therapy

Circular RNAs (circRNAs) are a special class of endogenous RNAs with a wide variety of pathophysiological functions via diverse mechanisms, including transcription, miRNA sponge, protein sponge/decoy, and translation. Stem cells are pluripotent cells with unique properties of self-renewal and differentiation. Dysregulated circRNAs identified in various stem cell types can affect stem cell self-renewal and differentiation potential by manipulating stemness. However, the emerging roles of circRNAs in stem cells remain largely unknown. This review summarizes the major functions and mechanisms of action of circRNAs in stem cell biology and disease progression. We also highlight circRNAs-mediated common pathways in diverse stem cell types and discuss their diagnostic significance with respect to stem cell-based therapy.

scholarly journals Cell-Based Therapy for Stroke

Stroke ◽  
2020 ◽  
Vol 51 (9) ◽  
pp. 2854-2862 ◽  
Author(s):  
You Jeong Park ◽  
Kuniyasu Niizuma ◽  
Maxim Mokin ◽  
Mari Dezawa ◽  
Cesar V. Borlongan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Cell Therapy ◽  
Therapeutic Potential ◽  
Host Tissue ◽  
In Vivo Models ◽  
Cell Based Therapy ◽  
Muse Cells

Stem cell-based regenerative therapies may rescue the central nervous system following ischemic stroke. Mesenchymal stem cells exhibit promising regenerative capacity in in vitro studies but display little to no incorporation in host tissue after transplantation in in vivo models of stroke. Despite these limitations, clinical trials using mesenchymal stem cells have produced some functional benefits ascribed to their ability to modulate the host’s inflammatory response coupled with their robust safety profile. Regeneration of ischemic brain tissue using stem cells, however, remains elusive in humans. Multilineage-differentiating stress-enduring (Muse) cells are a distinct subset of mesenchymal stem cells found sporadically in connective tissue of nearly every organ. Since their discovery in 2010, these endogenous reparative stem cells have been investigated for their therapeutic potential against a variety of diseases, including acute myocardial infarction, stroke, chronic kidney disease, and liver disease. Preclinical studies have exemplified Muse cells’ unique ability mobilize, differentiate, and engraft into damaged host tissue. Intravenously transplanted Muse cells in mouse lacunar stroke models afforded functional recovery and long-term engraftment into the host neural network. This mini-review article highlights these biological properties that make Muse cells an exceptional candidate donor source for cell therapy in ischemic stroke. Elucidating the mechanism behind the therapeutic potential of Muse cells will undoubtedly help optimize stem cell therapy for stroke and advance the field of regenerative medicine.

scholarly journals Effects of Neuropeptide Y on Stem Cells and Their Potential Applications in Disease Therapy

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Song Peng ◽  
You-li Zhou ◽  
Zhi-yuan Song ◽  
Shu Lin
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neuropeptide Y ◽  
Therapeutic Potential ◽  
Peripheral Tissues ◽  
Amino Acid Peptide ◽  
Cell Based Therapy ◽  
Disease Therapy ◽  
Potential Applications ◽  
Regulatory Effects

Neuropeptide Y (NPY), a 36-amino acid peptide, is widely distributed in the central and peripheral nervous systems and other peripheral tissues. It takes part in regulating various biological processes including food intake, circadian rhythm, energy metabolism, and neuroendocrine secretion. Increasing evidence indicates that NPY exerts multiple regulatory effects on stem cells. As a kind of primitive and undifferentiated cells, stem cells have the therapeutic potential to replace damaged cells, secret paracrine molecules, promote angiogenesis, and modulate immunity. Stem cell-based therapy has been demonstrated effective and considered as one of the most promising treatments for specific diseases. However, several limitations still hamper its application, such as poor survival and low differentiation and integration rates of transplanted stem cells. The regulatory effects of NPY on stem cell survival, proliferation, and differentiation may be helpful to overcome these limitations and facilitate the application of stem cell-based therapy. In this review, we summarized the regulatory effects of NPY on stem cells and discussed their potential applications in disease therapy.

scholarly journals Bioinformatics Analysis of Transcriptomic Data Reveals Refined Functional Networks for the Self-Renewal of Mouse Spermatogonial Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Min Wang ◽  
Wene Zhao ◽  
Fuqiang Wang ◽  
Xiufeng Ling ◽  
Daozhen Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathways ◽  
Bioinformatics Analysis ◽  
Cell Types ◽  
Spermatogonial Stem Cells ◽  
Expression Index ◽  
Extrinsic Factors ◽  
Self Renewal ◽  
Proliferation And Differentiation ◽  
Disease Associations

Spermatogonial stem cells (SSCs) are exquisitely regulated to reach a balance between proliferation and differentiation in the niche of seminiferous epithelium. Several extrinsic factors such as GDNF are reported to switch the transition, activating various intrinsic signaling pathways. Transcriptomics analysis could provide a comprehensive landscape of gene expression and regulation. Here, we reanalyzed a previously published transcriptome of two cell types (standing for self-renewing and differentiating SSCs correspondingly). First, we proposed a new parameter, the expression index, to sort the genes considering both absolute and relative expression levels. Using a dynamic statistical model, we identified a list of 1119 candidate genes for SSC self-renewal with the best enrichment of canonical markers. Finally, based on interaction relations, we further optimized the list and constructed a refined network containing integrated information of interactions, expression alternations, biological functions, and disease associations. Further annotation of the 521 refined genes involved in the network revealed an enrichment of well-studied signaling pathways. We believe that the refined network could help us better understand the regulation of SSCs’ fates, as well as find novel regulators or targets for SSC self-renewal or preservation of male fertility.

scholarly journals Commercial Production of Autologous Stem Cells and Their Therapeutic Potential for Liver Cirrhosis

2017 ◽  
Vol 26 (3) ◽  
pp. 449-460 ◽  
Author(s):  
Yi-Chun Lin ◽  
Horng-Jyh Harn ◽  
Po-Cheng Lin ◽  
Ming-Hsi Chuang ◽  
Chun-Hung Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Cirrhosis ◽  
Stem Cell ◽  
Therapeutic Potential ◽  
Dose Range ◽  
Tumor Development ◽  
Commercial Production ◽  
Production Program ◽  
Cell Based Therapy ◽  
Promising Source

Human adipose-derived stem cells (hADSCs) are a promising source of autologous stem cells for personalized cell-based therapies. Culture expansion of ADSCs provides an attractive opportunity for liver cirrhosis patients. However, safety and stability issues can pose big challenges for personalized autologous stem cell products. In the present study, we addressed whether the commercial production program could provide a consistent product for liver cirrhosis therapy. We collected adipose tissue from three human donors by lipoaspirate and isolated ADSCs, which were expanded in culture to reach 1 × 10 8 cells (an approximately 1,000-fold expansion) within four passages. We then examined their morphology, chromosome stability, surface markers, and differentiation ability after culture. Next, we explored their therapeutic potential using a rat model of thioacetamide-induced liver cirrhosis. Culture-expanded ADSCs were injected intrahepatically, and their biodistribution was tracked by immunohistochemistry using an antibody against human mitochondria. Finally, we tested for tumor development by subcutaneously injecting a 100-fold dose range of cultured ADSCs into immunocompromised mice. Taken together, we find that culture expansion of autologous ADSCs is a potentially suitable stem cell product for personalized cell-based therapy for patients with liver cirrhosis.

scholarly journals Interaction Between Mesenchymal Stem Cells and Retinal Degenerative Microenvironment

2021 ◽  
Vol 14 ◽  
Author(s):  
Yu Lin ◽  
Xiang Ren ◽  
Yongjiang Chen ◽  
Danian Chen
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Vision Loss ◽  
Therapeutic Potential ◽  
Clinical Stage ◽  
Retinal Disease ◽  
Tumor Formation ◽  
Cell Based Therapy ◽  
Retinal Degenerative Diseases ◽  
Stromal Stem Cells

Retinal degenerative diseases (RDDs) are a group of diseases contributing to irreversible vision loss with yet limited therapies. Stem cell-based therapy is a promising novel therapeutic approach in RDD treatment. Mesenchymal stromal/stem cells (MSCs) have emerged as a leading cell source due to their neurotrophic and immunomodulatory capabilities, limited ethical concerns, and low risk of tumor formation. Several pre-clinical studies have shown that MSCs have the potential to delay retinal degeneration, and recent clinical trials have demonstrated promising safety profiles for the application of MSCs in retinal disease. However, some of the clinical-stage MSC therapies have been unable to meet primary efficacy end points, and severe side effects were reported in some retinal “stem cell” clinics. In this review, we provide an update of the interaction between MSCs and the RDD microenvironment and discuss how to balance the therapeutic potential and safety concerns of MSCs' ocular application.

scholarly journals New insights into mitophagy and stem cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qingyin Lin ◽  
Jiaqi Chen ◽  
Lifang Gu ◽  
Xingang Dan ◽  
Cheng Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Nutrient Deficiency ◽  
Metabolic Stress ◽  
Future Research ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Proliferation And Differentiation ◽  
Tissue Aging ◽  
Stress Damage

AbstractMitophagy is a specific autophagic phenomenon in which damaged or redundant mitochondria are selectively cleared by autophagic lysosomes. A decrease in mitophagy can accelerate the aging process. Mitophagy is related to health and longevity and is the key to protecting stem cells from metabolic stress damage. Mitophagy decreases the metabolic level of stem cells by clearing active mitochondria, so mitophagy is becoming increasingly necessary to maintain the regenerative capacity of old stem cells. Stem cell senescence is the core problem of tissue aging, and tissue aging occurs not only in stem cells but also in transport amplifying cell chambers and the stem cell environment. The loss of the autophagic ability of stem cells can cause the accumulation of mitochondria and the activation of the metabolic state as well as damage the self-renewal ability and regeneration potential of stem cells. However, the claim remains controversial. Mitophagy is an important survival strategy against nutrient deficiency and starvation, and mitochondrial function and integrity may affect the viability, proliferation and differentiation potential, and longevity of normal stem cells. Mitophagy can affect the health and longevity of the human body, so the number of studies in this field has increased, but the mechanism by which mitophagy participates in stem cell development is still not fully understood. This review describes the potential significance of mitophagy in stem cell developmental processes, such as self-renewal, differentiation and aging. Through this work, we discovered the role and mechanism of mitophagy in different types of stem cells, identified novel targets for killing cancer stem cells and curing cancer, and provided new insights for future research in this field.

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