Platelets Promote Pro-Angiogenic Activity of Mesenchymal Stem Cells Via Mitochondrial Transfer and Metabolic Reprogramming

2020 ◽  
Author(s):  
Jennyfer Levoux ◽  
Alexandre Prola ◽  
Peggy Lafuste ◽  
Marianne Gervais ◽  
Laura Braud ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Metabolic Reprogramming ◽  
Angiogenic Activity ◽  
Mitochondrial Transfer

scholarly journals Platelets facilitate the wound-healing capability of mesenchymal stem cells by mitochondrial transfer and metabolic reprogramming

2021 ◽  
Vol 33 (3) ◽  
pp. 688-690
Author(s):  
Jennyfer Levoux ◽  
Alexandre Prola ◽  
Peggy Lafuste ◽  
Marianne Gervais ◽  
Nathalie Chevallier ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Metabolic Reprogramming ◽  
Mitochondrial Transfer

scholarly journals CD157 in bone marrow mesenchymal stem cells mediates mitochondrial production and transfer to improve neuronal apoptosis and functional recovery after spinal cord injury

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Li ◽  
Heyangzi Li ◽  
Simin Cai ◽  
Shi Bai ◽  
Huabo Cai ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Motor Neurons ◽  
Functional Recovery ◽  
Mitochondrial Transfer ◽  
Cord Injury ◽  
Marrow Mesenchymal Stem Cells

Abstract Background Recent studies demonstrated that autologous mitochondria derived from bone marrow mesenchymal stem cells (BMSCs) might be valuable in the treatment of spinal cord injury (SCI). However, the mechanisms of mitochondrial transfer from BMSCs to injured neurons are not fully understood. Methods We modified BMSCs by CD157, a cell surface molecule as a potential regulator mitochondria transfer, then transplanted to SCI rats and co-cultured with OGD injured VSC4.1 motor neuron. We detected extracellular mitochondrial particles derived from BMSCs by transmission electron microscope and measured the CD157/cyclic ADP-ribose signaling pathway-related protein expression by immunohistochemistry and Western blotting assay. The CD157 ADPR-cyclase activity and Fluo-4 AM was used to detect the Ca2+ signal. All data were expressed as mean ± SEM. Statistical analysis was analyzed by GraphPad Prism 6 software. Unpaired t-test was used for the analysis of two groups. Multiple comparisons were evaluated by one-way ANOVA or two-way ANOVA. Results CD157 on BMSCs was upregulated when co-cultured with injured VSC4.1 motor neurons. Upregulation of CD157 on BMSCs could raise the transfer extracellular mitochondria particles to VSC4.1 motor neurons, gradually regenerate the axon of VSC4.1 motor neuron and reduce the cell apoptosis. Transplantation of CD157-modified BMSCs at the injured sites could significantly improve the functional recovery, axon regeneration, and neuron apoptosis in SCI rats. The level of Ca2+ in CD157-modified BMSCs dramatically increased when objected to high concentration cADPR, ATP content, and MMP of BMSCs also increased. Conclusion The present results suggested that CD157 can regulate the production and transfer of BMSC-derived extracellular mitochondrial particles, enriching the mechanism of the extracellular mitochondrial transfer in BMSCs transplantation and providing a novel strategy to improve the stem cell treatment on SCI.

Role of psoriatic keratinocytes in the metabolic reprogramming of dermal mesenchymal stem cells

2021 ◽  
Author(s):  
Yue Cao ◽  
Nan‐Nan Liang ◽  
Wen‐Juan Chang ◽  
Jun‐Qin Li ◽  
Juan‐Juan Jiao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Metabolic Reprogramming

scholarly journals VCAM-1+ placenta chorionic villi-derived mesenchymal stem cells display potent pro-angiogenic activity

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Wenjing Du ◽  
Xue Li ◽  
Ying Chi ◽  
Fengxia Ma ◽  
Zongjin Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Chorionic Villi ◽  
Angiogenic Activity

scholarly journals Mesenchymal stem cells and their mitochondrial transfer: a double-edged sword

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Cheng Li ◽  
Marco K.H. Cheung ◽  
Shuo Han ◽  
Zhao Zhang ◽  
Ling Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Tissue Repair ◽  
Cancer Metastasis ◽  
Cell Injury ◽  
Tissue Degeneration ◽  
Cell Based Therapy ◽  
Mitochondrial Transfer

Abstract Mitochondrial dysfunction has been linked to many diseases including organ degeneration and cancer. Mesenchymal stem cells/stromal cells (MSCs) provide a valuable source for stem cell-based therapy and represent an emerging therapeutic approach for tissue regeneration. Increasing evidence suggests that MSCs can directly donate mitochondria to recover from cell injury and rescue mitochondrial damage-provoked tissue degeneration. Meanwhile, cancer cells and cancer stromal cells also cross-talk through mitochondrial exchange to regulate cancer metastasis. This review summarizes the research on MSCs and their mitochondrial transfer. It provides an overview of the biology, function, niches and signaling that play a role in tissue repair. It also highlights the pathologies of cancer growth and metastasis linked to mitochondrial exchange between cancer cells and surrounding stromal cells. It becomes evident that the function of MSC mitochondrial transfer is a double-edged sword. MSC mitochondrial transfer may be a pharmaceutical target for tissue repair and cancer therapy.

Improving of survival, angiogenic activity and efficiency of mesenchymal stem cells by melatonin injected in infarcted heart

2008 ◽  
Vol 44 (4) ◽  
pp. 712
Author(s):  
Céline Mias ◽  
Marie-Hélène Seguelas ◽  
Olivier Lairez ◽  
Elodie Trouche ◽  
Françoise Dignat-George ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Angiogenic Activity ◽  
Infarcted Heart

scholarly journals CD157 mediates mitochondrial production and transfer from bone marrow mesenchymal stem cells (BMSCs) to improve neuronal apoptosis and functional recovery after spinal cord injury

2020 ◽  
Author(s):  
Jing Li ◽  
Heyangzi Li ◽  
Simin Cai ◽  
Shi Bai ◽  
Huabo Cai ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Motor Neurons ◽  
Functional Recovery ◽  
Mitochondrial Transfer ◽  
Cord Injury ◽  
Marrow Mesenchymal Stem Cells

Abstract Background: Recent studies demonstrated that autologous mitochondria derived from bone marrow mesenchymal stem cells (BMSCs) might be valuable in the treatment of spinal cord injury (SCI). However, the mechanisms of mitochondrial transfer from BMSCs to injured neurons are not fully understood. Methods: We modified BMSCs by CD-157, a cell surface molecule as a potential regulator mitochondria transfer, then transplanted to SCI rats and co-cultured with OGD injured VSC4.1 motor neuron. We detected extracellular mitochondrial particles derived from BMSCs by transmission electron microscope and measured the CD157/cyclic ADP-ribose signaling pathway related protein expression by immunohistochemistry and Western blotting assay. The CD157 ADPR-cyclase activity and Fluo-4 AM was used to detect the Ca2+ signal. All data were expressed as mean ± SEM. Statistical analysis was analyzed by GraphPad Prism 6 software. Unpaired t-test was used for the analysis of two groups. Multiple comparisons were evaluated by one-way ANOVA or two-way ANOVA.Results: CD157 on BMSCs was upregulated when co-cultured with injured VSC4.1 motor neurons. Upregulation of CD157 on BMSCs could raise the transfer extracellular mitochondria particles to VSC4.1 motor neurons, gradually regenerate the axon of VSC4.1 motor neuron and reduce the cell apoptosis. Transplantation of CD157 modified BMSCs at the injured sites could significantly improve the functional recovery, axon regeneration and neuron apoptosis in SCI rats. The level of Ca2+ in CD157 modified BMSCs dramatically increased and when objected to high concentration cADPR, ATP content and MMP of BMSCs also increased.Conclusion: This study evidences that CD157 can regulate the produce and transfer of BMSCs-derived extracellular mitochondrial particles, enriching the mechanism of the extracellular mitochondrial transfer in BMSCs transplantation and providing a novel strategy to improve the stem cell treatment on SCI.

scholarly journals Succinate Supplement Elicited “Pseudohypoxia” Condition to Promote Proliferation, Migration, and Osteogenesis of Periodontal Ligament Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Huimin Mao ◽  
Andi Yang ◽  
Yunhe Zhao ◽  
Lang Lei ◽  
Houxuan Li
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Oxidative Phosphorylation ◽  
Periodontal Ligament ◽  
Cell Metabolism ◽  
Tca Cycle ◽  
Metabolic Reprogramming ◽  
Periodontal Ligament Cells ◽  
Low Oxygen

Most mesenchymal stem cells reside in a niche of low oxygen tension. Iron-chelating agents such as CoCl2 and deferoxamine have been utilized to mimic hypoxia and promote cell growth. The purpose of the present study was to explore whether a supplement of succinate, a natural metabolite of the tricarboxylic acid (TCA) cycle, can mimic hypoxia condition to promote human periodontal ligament cells (hPDLCs). Culturing hPDLCs in hypoxia condition promoted cell proliferation, migration, and osteogenic differentiation; moreover, hypoxia shifted cell metabolism from oxidative phosphorylation to glycolysis with accumulation of succinate in the cytosol and its release into culture supernatants. The succinate supplement enhanced hPDLC proliferation, migration, and osteogenesis with decreased succinate dehydrogenase (SDH) expression and activity, as well as increased hexokinase 2 (HK2) and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), suggesting metabolic reprogramming from oxidative phosphorylation to glycolysis in a normal oxygen condition. The succinate supplement in cell cultures promoted intracellular succinate accumulation while stabilizing hypoxia inducible factor-1α (HIF-1α), leading to a state of pseudohypoxia. Moreover, we demonstrate that hypoxia-induced proliferation was G-protein-coupled receptor 91- (GPR91-) dependent, while exogenous succinate-elicited proliferation involved the GPR91-dependent and GPR91-independent pathway. In conclusion, the succinate supplement altered cell metabolism in hPDLCs, induced a pseudohypoxia condition, and enhanced proliferation, migration, and osteogenesis of mesenchymal stem cells in vitro.

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