Novel Strategy to Engineer Trachea Cartilage Graft With Marrow Mesenchymal Stem Cell Macroaggregate and Hydrolyzable Scaffold

Mesenchymal stem cell- (MSC-) based therapy is a novel strategy in regenerative medicine. The functional and regenerative capacities of MSCs decline with senescence. Nonetheless, the potential mechanisms that underlie their senescence are not fully understood. This study was aimed at exploring the potential mechanisms of fibroblast growth factor 21 (FGF21) in the regulation of MSC senescence. The senescence of MSCs was determined by senescence-associated β-galactosidase (SA-β-gal) staining. The morphology and the level of mitochondrial reactive oxygen species (ROS) of MSCs were assessed by MitoTracker and Mito-Sox staining, respectively. The expression of FGF21 and mitochondrial dynamics-related proteins was detected by Western blotting. As MSCs were expanded in vitro, the expression of FGF21 decreased. Depletion of FGF21 enhanced production of mitochondrial reactive oxidative species (ROS) and increased the senescence of early-passage MSCs whereas inhibition of ROS abolished these effects. The senescent MSCs exhibited increased mitochondrial fusion and decreased mitochondrial fission. Treatment of early-passage MSCs with FGF21 siRNA enhanced mitochondrial fusion and reduced mitochondrial fission. Moreover, treatment of mitofusin2- (Mfn2-) siRNA inhibited depletion of FGF21-induced MSC senescence. Furthermore, we demonstrated that depletion of FGF21-induced mitochondrial fusion was regulated by the AMPK signaling pathway. Treatment with an AMPK activator, AICAR, abrogated the depletion of FGF21-induced senescence of MSCs by inhibiting mitochondrial fusion. Compared with MSCs isolated from young donors, those derived from aged donors showed a lower level of FGF21 and a higher level of senescent activity. Furthermore, overexpression of FGF21 in aged MSCs inhibited senescence. Our study shows that FGF21, via the AMPK signaling pathway, regulates the senescence of MSCs by mediating mitochondrial dynamics. Targeting FGF21 might represent a novel strategy to improve the quality and quantity of MSCs.

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A Novel Strategy to Enhance Mesenchymal Stem Cell Migration Capacity and Promote Tissue Repair in an Injury Specific Fashion

Cell Transplantation ◽

10.3727/096368912x653246 ◽

2013 ◽

Vol 22 (3) ◽

pp. 423-436 ◽

Cited By ~ 74

Author(s):

C. Xinaris ◽

M. Morigi ◽

V. Benedetti ◽

B. Imberti ◽

A. S. Fabricio ◽

...

Keyword(s):

Stem Cell ◽

Cell Migration ◽

Mesenchymal Stem Cell ◽

Tissue Repair ◽

Stem Cell Migration ◽

Novel Strategy ◽

Migration Capacity

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Adult mesenchymal stem cell ageing interplays with depressed mitochondrial Ndufs6

Cell Death and Disease ◽

10.1038/s41419-020-03289-w ◽

2020 ◽

Vol 11 (12) ◽

Author(s):

Yuelin Zhang ◽

Liyan Guo ◽

Shuo Han ◽

Ling Chen ◽

Cheng Li ◽

...

Keyword(s):

Stem Cell ◽

Mesenchymal Stem Cell ◽

Adult Stem Cells ◽

Adult Stem Cell ◽

Mitochondrial Ros ◽

Ros Accumulation ◽

Sulfur Protein ◽

Aged State ◽

Novel Strategy ◽

Underlying Mechanisms

AbstractMesenchymal stem cell (MSC)-based therapy has emerged as a novel strategy to treat many degenerative diseases. Accumulating evidence shows that the function of MSCs declines with age, thus limiting their regenerative capacity. Nonetheless, the underlying mechanisms that control MSC ageing are not well understood. We show that compared with bone marrow-MSCs (BM-MSCs) isolated from young and aged samples, NADH dehydrogenase (ubiquinone) iron-sulfur protein 6 (Ndufs6) is depressed in aged MSCs. Similar to that of Ndufs6 knockout (Ndufs6−/−) mice, MSCs exhibited a reduced self-renewal and differentiation capacity with a tendency to senescence in the presence of an increased p53/p21 level. Downregulation of Ndufs6 by siRNA also accelerated progression of wild-type BM-MSCs to an aged state. In contrast, replenishment of Ndufs6 in Ndufs6−/−-BM-MSCs significantly rejuvenated senescent cells and restored their proliferative ability. Compared with BM-MSCs, Ndufs6−/−-BM-MSCs displayed increased intracellular and mitochondrial reactive oxygen species (ROS), and decreased mitochondrial membrane potential. Treatment of Ndufs6−/−-BM-MSCs with mitochondrial ROS inhibitor Mito-TEMPO notably reversed the cellular senescence and reduced the increased p53/p21 level. We provide direct evidence that impairment of mitochondrial Ndufs6 is a putative accelerator of adult stem cell ageing that is associated with excessive ROS accumulation and upregulation of p53/p21. It also indicates that manipulation of mitochondrial function is critical and can effectively protect adult stem cells against senescence.

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Combining mesenchymal stem cell sheets with platelet-rich plasma gel/calcium phosphate particles: a novel strategy to promote bone regeneration

Stem Cell Research & Therapy ◽

10.1186/s13287-015-0256-1 ◽

2015 ◽

Vol 6 (1) ◽

Cited By ~ 29

Author(s):

Yiying Qi ◽

Lie Niu ◽

Tengfei Zhao ◽

Zhongli Shi ◽

Tuoyu Di ◽

...

Keyword(s):

Stem Cell ◽

Calcium Phosphate ◽

Mesenchymal Stem Cell ◽

Bone Regeneration ◽

Platelet Rich Plasma ◽

Cell Sheets ◽

Calcium Phosphate Particles ◽

Novel Strategy

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Mesenchymal Stem Cell-Based Therapy for Stroke: Current Understanding and Challenges

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.628940 ◽

2021 ◽

Vol 15 ◽

Author(s):

Weifeng Li ◽

Linli Shi ◽

Bei Hu ◽

Yimei Hong ◽

Hao Zhang ◽

...

Keyword(s):

Stem Cell ◽

Mesenchymal Stem Cell ◽

Scientific Data ◽

Functional Rehabilitation ◽

Differentiation Potential ◽

Cell Based Therapy ◽

Multipotent Differentiation ◽

Novel Strategy ◽

Therapy Treatment

Stroke, the most prevalent cerebrovascular disease, causes serious loss of neurological function and is the leading cause of morbidity and mortality worldwide. Despite advances in pharmacological and surgical therapy, treatment for functional rehabilitation following stroke is limited with a consequent serious impact on quality of life. Over the past decades, mesenchymal stem cell (MSCs)-based therapy has emerged as a novel strategy for various diseases including stroke due to their unique properties that include easy isolation, multipotent differentiation potential and strong paracrine capacity. Although MSCs have shown promising results in the treatment of stroke, there remain many challenges to overcome prior to their therapeutic application. In this review, we focus on the following issues: the scientific data from preclinical studies and clinical trials of MSCs in the treatment of stroke; the potential mechanisms underlying MSC-based therapy for stroke; the challenges related to the timing and delivery of MSCs and MSC senescence.

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