Aging of mesenchymal stem cells: Implication in regenerative medicine

Yang, Yueh Hsun

doi:10.1016/j.reth.2018.09.002

Cited by 76 publications

(59 citation statements)

References 44 publications

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“…Human mesenchymal stem cells (hMSCs) support the maintenance of other cell populations in the body and have the potential to differentiate into diverse cell lineages, such as chondrocytes, osteoblasts, and adipocytes (Uccelli et al, 2008;Dimarino et al, 2013;Obeid et al, 2013). Not entirely surprisingly, progressive exhaustion of the hMSC pool has been causally linked to aging-associated tissue malfunction and degenerative diseases (Zhou et al, 2008;Zhang et al, 2011;Yang, 2018). In premature aging diseases like Hutchinson-Gilford progeria syndrome (HGPS), the hMSC population also undergoes accelerated decay with features of classic cellular senescence (Stenderup et al, 2003;Kudlow et al, 2007;Liu et al, 2011;Kubben et al, 2016;Wu et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer

Liu

et al. 2020

Protein Cell

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SIRT7, a sirtuin family member implicated in aging and disease, is a regulator of metabolism and stress responses. It remains elusive how human somatic stem cell populations might be impacted by SIRT7. Here, we found that SIRT7 expression declines during human mesenchymal stem cell (hMSC) aging and that SIRT7 deficiency accelerates senescence. Mechanistically, SIRT7 forms a complex with nuclear lamina proteins and heterochromatin proteins, thus maintaining the repressive state of heterochromatin at nuclear periphery. Accordingly, deficiency of SIRT7 results in loss of heterochromatin, de-repression of the LINE1 retrotransposon (LINE1), and activation of innate immune signaling via the cGAS-STING pathway. These agingassociated cellular defects were reversed by overexpression of heterochromatin proteins or treatment with a LINE1 targeted reverse-transcriptase inhibitor. Together, these findings highlight how SIRT7 safeguards chromatin architecture to control innate immune regulation and ensure geroprotection during stem cell aging.

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Section: Introductionmentioning

confidence: 99%

SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer

Liu

et al. 2020

Protein Cell

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“…While MSCs have become an increasingly utilized novel therapeutic for the treatment of perianal stulizing CD, there are several limitations of cell-based therapy including cost and scalability of manufacturing, short shelf life, and cell-to-cell variability in e cacy which can all lead to prohibitive costs and low reproducibility. (40,41) Thus, there has been signi cant consideration for how to overcome these limitations of cell-based therapy. One area of increasing interest is acellular therapy, which includes the microparticles secreted by MSCs termed extracellular vesicles (EVs).…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells and Acelluar Products Attenuate Murine Induced Colitis

Altemus

Lightner

2020

Preprint

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Background: Mesenchymal stem cells (MSCs) are a well-established immunosuppressive agent which can also promote tissue repair and regeneration. Recent studies have demonstrated MSCs as a novel therapeutic for inflammatory bowel disease (IBD), a chronic idiopathic inflammatory disorder of the gastrointestinal tract. However, the precise role of MSCs in regulating immune-responses is controversial, and its significance in the pathogenesis of IBD uncertain. In addition, MSCs’ acellular product, extracellular vesicles (EVs), may also play an important role in the armamentarium of therapeutics, but how EVs compare to MSCs remains undefined due to the lack of side-by-side comparative investigation. We herein compared MSCs and their associated EVs side-by-side using a DSS-induced colitis model. Methods: A DSS-induced colitis model was used. At Day 4, mice received adipose derived MSCs, MSC derived EVs, or placebo. Weight loss, stool consistency and hematochezia was charted. At day 8, murine colons were harvested, histologic analysis performed, and serum/tissue cytokine analysis conducted. Results: MSCs and EVs demonstrated equivalent immunosuppressive functions with DSS-treated mice through decreased colonic lymphocyte infiltration and attenuated disease severity after both MSC and EV treatment. Furthermore, both MSCs and EVs have an equivalent ability to inhibit inflammation in the DSS colitis model. Conclusions: These results suggest that (i) both MSCs and EVs are effective therapeutic candidates for a DSS-induced mouse colitis model, (ii) MSCs and EVs have similar immunosuppressive and anti-inflammatory functions, and (iii) EVs may present a novel future therapeutic for the treatment of IBD.

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“…While MSCs have become an increasingly utilized novel therapeutic for the treatment of perianal stulizing CD, there are several limitations of cell-based therapy including cost and scalability of manufacturing, short shelf life, and cell-to-cell variability in e cacy which can all lead to prohibitive costs and low reproducibility. (48,49) Thus, there has been signi cant consideration for how to overcome these limitations of cell-based therapy. One area of increasing interest is acellular therapy, which includes the microparticles secreted by MSCs termed extracellular vesicles (EVs).…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells and Acelluar Products Attenuate Murine Induced Colitis

Altemus

Lightner

2020

Preprint

View full text Add to dashboard Cite

Background: Mesenchymal stem cells (MSCs) are a well-established immunomodulatory agent which can also promote tissue repair and regeneration. Recent studies have demonstrated MSCs as a novel therapeutic for inflammatory bowel disease (IBD), a chronic idiopathic inflammatory disorder of the gastrointestinal tract. However, the precise role of MSCs in regulating immune responses is controversial, and its significance in the pathogenesis remains IBD undefined. In addition, MSCs’ acellular product, extracellular vesicles (EVs), may also play an important role in the armamentarium of therapeutics, but how EVs compare to MSCs remains unknown due to the lack of side-by-side comparative investigation. We herein compared MSCs and MSC-derived EVs for the treatment of IBD using a DSS-induced colitis model. Methods: A DSS-induced colitis model was used. At Day 4, mice received adipose derived MSCs, MSC-derived EVs, or placebo. Weight loss, stool consistency and hematochezia was charted. At day 8, murine colons were harvested, histologic analysis performed, and serum/tissue cytokine analysis conducted. Results: MSCs and EVs demonstrated equivalent immunosuppressive function in DSS-treated mice through decreased colonic lymphocyte infiltration and attenuated disease severity after both MSC and EV treatment. Importantly, the ability to inhibit inflammation in the DSS colitis model was equivalent for both MSCs and MSC-derived EVs. Conclusions: These results suggest that (i) both MSCs and EVs are effective therapeutic candidates for a DSS-induced mouse colitis model, (ii) MSCs and EVs have similar immunosuppressive and anti-inflammatory functions, and (iii) EVs may present a novel future therapeutic for the treatment of IBD.

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Aging of mesenchymal stem cells: Implication in regenerative medicine

Cited by 76 publications

References 44 publications

SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer

SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer

Mesenchymal Stem Cells and Acelluar Products Attenuate Murine Induced Colitis

Mesenchymal Stem Cells and Acelluar Products Attenuate Murine Induced Colitis

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