Anti-apoptotic Effects of Human Wharton's Jelly-derived Mesenchymal Stem Cells on Skeletal Muscle Cells Mediated via Secretion of XCL1

Kwon, Soojin; Ki, Soo Mi; Park, Sang Eon; Kim, Minjeong; Hyung, Brian; Lee, Na Kyung; Shim, Sangmi; Choi, Byung‐Ok; Na, Duk L.; Lee, Ji Eun; Chang, Jong Wook

doi:10.1038/mt.2016.125

Cited by 43 publications

(43 citation statements)

References 47 publications

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“…The multiple roles of apoptosis in regulating various physiological and pathological functions implicate its significance in disease treatment [198]. Moreover, MSCs can synthesise and secrete B-cell lymphoma 2 (BCL-2), survivin, VEGF, HGF, insulin-like growth factor-I (IGF-I), stanniocalcin-1 (STC1), TGF-β, FGF, and granulocyte-macrophage colonystimulating factor (GM-CSF), which inhibit cellular apoptosis and restore tissue homeostasis [198][199][200][201][202][203]. BCL-2 is a classic inhibitor of apoptosis.…”

Section: Anti-apoptotic Factorsmentioning

confidence: 99%

“…Meanwhile, MSC-conditioned medium could down-regulate Bax, TNF receptor superfamily, member 6 (FAS), and caspase 3 (CASP3) levels in a human normal liver cell line under ischemic conditions, indicating the anti-apoptotic effects of MSC paracrine function [208]. MSC-derived chemokine (C motif) ligand (XCL1) has been reported to inhibit apoptosis in C2C12 cells [198]. However, direct XCL1 treatment showed no anti-apoptotic capacity.…”

Section: Anti-apoptotic Factorsmentioning

confidence: 99%

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Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

Fan

Zhang

et al. 2020

Cell. Mol. Life Sci.

372

282

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Mesenchymal stem cells (MSCs) have been extensively investigated for the treatment of various diseases. The therapeutic potential of MSCs is attributed to complex cellular and molecular mechanisms of action including differentiation into multiple cell lineages and regulation of immune responses via immunomodulation. The plasticity of MSCs in immunomodulation allow these cells to exert different immune effects depending on different diseases. Understanding the biology of MSCs and their role in treatment is critical to determine their potential for various therapeutic applications and for the development of MSC-based regenerative medicine. This review summarizes the recent progress of particular mechanisms underlying the tissue regenerative properties and immunomodulatory effects of MSCs. We focused on discussing the functional roles of paracrine activities, direct cell-cell contact, mitochondrial transfer, and extracellular vesicles related to MSC-mediated effects on immune cell responses, cell survival, and regeneration. This will provide an overview of the current research on the rapid development of MSC-based therapies. Keywords Regenerative potential • Integration of MSCs • Immunomodulation • Soluble factors • Cell-cell contact • Mitochondrial transfer • Extracellular vesicles Abbreviations AHR Airway hyper-responsiveness Alix ALG-2-interacting protein X Ang-1 Angiopoietin-1 ASCs Adipose-derived stem cells BAX BCL-2-associated X protein BCL-2 B-cell lymphoma 2 CASP3 Caspase 3 CX43 Connexin 43 CXCR4 Chemokine receptor type 4 DC Dendritic cell Cellular and Molecular Life Sciences

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Section: Anti-apoptotic Factorsmentioning

confidence: 99%

Section: Anti-apoptotic Factorsmentioning

confidence: 99%

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

Fan

Zhang

et al. 2020

Cell. Mol. Life Sci.

372

282

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“…The mouse cells mirror the biology of human cells well in various aspects (33). Previous studies (34)(35)(36) have also demonstrated that human cells and/or their cM have protective effects in mouse and rat cells. Therefore, c2c12 cells were used in the present study.…”

Section: Introductionmentioning

confidence: 91%

The secretome of human dental pulp stem cells protects myoblasts from hypoxia‑induced injury via the Wnt/β‑catenin pathway

Zhang

Han

et al. 2020

Int J Mol Med

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Human dental pulp stem cells (hdPScs) present several advantages, including their ability to be non-invasively harvested without ethical concern. The secretome of hdPScs can promote the functional recovery of various tissue injuries. However, the protective effects on hypoxia-induced skeletal muscle injury remain to be explored. The present study demonstrated that c2c12 myoblast coculture with hdPScs attenuated cocl 2-induced hypoxic injury compared with c2c12 alone. The hdPSc secretome increased cell viability and differentiation and decreased G2/M cell cycle arrest under hypoxic conditions. These results were further verified using hDPSC-conditioned medium (hDPSC-CM). The present data revealed that the protective effects of hdPSc-cM depend on the concentration ratio of the cM. In terms of the underlying molecular mechanism, hdPSc-cM activated the Wnt/β-catenin pathway, which increased the protein levels of Wnt1, phosphorylated-glycogen synthase kinase-3β and β-catenin and the mRNA levels of Wnt target genes. By contrast, an inhibitor (XAV939) of Wnt/β-catenin diminished the protective effects of hdPSc-cM. Taken together, the findings of the present study demonstrated that the hDPSC secretome alleviated the hypoxia-induced myoblast injury potentially through regulating the Wnt/β-catenin pathway. These findings may provide new insight into a therapeutic alternative using the hdPSc secretome in skeletal muscle hypoxia-related diseases.

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“…Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) were isolated according to the procedure described by Kwon [21]. The WJ-MSCs were cultured according to the standard operating procedures (SOPs) of the Good Manufacturing Practice facility at Samsung Medical Center.…”

Section: Wharton's Jelly-derived Mesenchymal Stem Cell Culturementioning

confidence: 99%

“…At least 10,000 events were acquired on a BD FACSVerse (BD Biosciences, NJ, USA), and the results were analyzed with BD FACSuite software version 10 (BD Biosciences, USA). The differentiation of pre-conditioned WJ-MSCs was analyzed according to the procedure outlined in a previous report [21].…”

Section: Flow-cytometry Analysis For Validating Re-conditioned Wj-mscsmentioning

confidence: 99%

Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic Effects

Park

Kim²,

Kwon³

et al. 2020

Preprint

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BackgroundMesenchymal stem cells (MSCs) have emerged as a promising tool for the treatment of Alzheimer’s disease (AD). Previous studies suggested that the co-culture of human MSCs with AD in an in vitro model reduced the expression of amyloid-beta 42 (Aβ42) in the medium as well as the overexpression of amyloid-beta (Aβ )-degrading enzymes such as neprilysin (NEP).MethodsIn this study, we focused on the role of primed MSCs (human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) exposed to an AD cell line via a co-culture system) in reducing the levels of Aβ and inhibiting cell death. ResultsWe demonstrated that mouse groups treated with naïve MSCs and primed MSCs showed significant reductions in cell death, ubiquitin conjugate levels, and Aβ levels, but the effects were greater in primed MSCs. Also, mRNA sequencing data analysis indicated that high levels of TGF-β induced primed-MSCs. Furthermore, treatment with TGF-β reduced Aβ expression in an AD transgenic mouse model. ConclusionAD environmental preconditioning is a promising strategy to reduce cell death and ubiquitin conjugate levels and maintain the stemness of MSCs. Further, these data suggest that human WJ-MSCs exposed to an AD environment may represent a promising and novel therapy for AD.

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Anti-apoptotic Effects of Human Wharton's Jelly-derived Mesenchymal Stem Cells on Skeletal Muscle Cells Mediated via Secretion of XCL1

Cited by 43 publications

References 47 publications

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

The secretome of human dental pulp stem cells protects myoblasts from hypoxia‑induced injury via the Wnt/β‑catenin pathway

Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic Effects

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