Hypoxia preconditioned bone marrow-derived mesenchymal stromal/stem cells enhance myoblast fusion and skeletal muscle regeneration

Archacka, Karolina; Grabowska, Iwona; Mierzejewski, Bartosz; Graffstein, Joanna; Górzyńska, Alicja; Krawczyk, Marta; Różycka, Anna M; Kalaszczyńska, Ilona; Muras, Gabriela; Stremińska, Władysława; Jańczyk-Ilach, Katarzyna; Walczak, Piotr; Janowski, Mirosław; Ciemerych, Maria A.; Brzóska, Edyta

doi:10.1186/s13287-021-02530-3

Cited by 35 publications

(24 citation statements)

References 106 publications

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“…Transplantation of hypoxia-preconditioned BMSCs into the damaged muscles in in vivo models improved the cell engraftment performance via the formation of new vessels. Among the molecules fundamental for better engraftment and angiogenesis, SDF-1 and VEGF-A secreted by the MSCs in question have been identified [4]. Fang Wang et al reported that 5% hypoxia exposure increased the differentiation of adipose tissue-derived MSCs into smooth muscle cells.…”

Section: Hypoxia and Stem Cellsmentioning

confidence: 99%

Hypoxia: molecular pathophysiological mechanisms in human diseases

et al. 2022

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Hypoxia, a low O2 tension, is a fundamental feature that occurs in physiological events as well as pathophysiological conditions, especially mentioned for its role in the mechanism of angiogenesis, glucose metabolism, and cell proliferation/survival. The hypoxic state through the activation of specific mechanisms is an aggravating circumstance commonly noticed in multiple sclerosis, cancer, heart disease, kidney disease, liver disease, lung disease, and in inflammatory bowel disease. On the other hand, hypoxia could play a key role in tissue regeneration and repair of damaged tissues, especially by acting on specific tissue stem cells, but their features may result as a disadvantage when it is concerned for neoplastic stem cells. Furthermore, hypoxia could also have a potential role in tissue engineering and regenerative medicine due to its capacity to improve the performance of biomaterials. The current review aims to highlight the hypoxic molecular mechanisms reported in different pathological conditions to provide an overview of hypoxia as a therapeutic agent in regenerative and molecular therapy. Graphical abstract

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Section: Hypoxia and Stem Cellsmentioning

confidence: 99%

Hypoxia: molecular pathophysiological mechanisms in human diseases

et al. 2022

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“…In cocultures they rarely fused with myoblasts. We previously showed that BMSC fusion with myoblasts is possible - hypoxic condition increased this process [ 53 ]. In the present study, we documented that the presence of miR151 or miR5100 transfected mouse BMSCs also increased human myoblast fusion.…”

Section: Discussionmentioning

confidence: 99%

The miR151 and miR5100 Transfected Bone Marrow Stromal Cells Increase Myoblast Fusion in IGFBP2 Dependent Manner

Mierzejewski

Michalska

Jackowski

et al. 2022

Stem Cell Rev and Rep

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Background Bone marrow stromal cells (BMSCs) form a perivascular cell population in the bone marrow. These cells do not present naïve myogenic potential. However, their myogenic identity could be induced experimentally in vitro or in vivo. In vivo, after transplantation into injured muscle, BMSCs rarely fused with myofibers. However, BMSC participation in myofiber reconstruction increased if they were modified by NICD or PAX3 overexpression. Nevertheless, BMSCs paracrine function could play a positive role in skeletal muscle regeneration. Previously, we showed that SDF-1 treatment and coculture with myofibers increased BMSC ability to reconstruct myofibers. We also noticed that SDF-1 treatment changed selected miRNAs expression, including miR151 and miR5100. Methods Mouse BMSCs were transfected with miR151 and miR5100 mimics and their proliferation, myogenic differentiation, and fusion with myoblasts were analyzed. Results We showed that miR151 and miR5100 played an important role in the regulation of BMSC proliferation and migration. Moreover, the presence of miR151 and miR5100 transfected BMSCs in co-cultures with human myoblasts increased their fusion. This effect was achieved in an IGFBP2 dependent manner. Conclusions Mouse BMSCs did not present naïve myogenic potential but secreted proteins could impact myogenic cell differentiation. miR151 and miR5100 transfection changed BMSC migration and IGFBP2 and MMP12 expression in BMSCs. miR151 and miR5100 transfected BMSCs increased myoblast fusion in vitro. Graphical abstract

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“…However, a previous study demonstrated that lifelong reduction of satellite cells neither accelerated nor exacerbated sarcopenia and that satellite cells did not contribute to the maintenance of muscle size or fiber type composition during aging, but that their loss may contribute to age-related muscle fibrosis [ 48 ]. On the other hand, recent accumulating evidence indicates that bone marrow- (BM-) derived cells participate in skeletal muscle regeneration in several animal models [ 13 – 15 ]. In recent experiments, we found that transplantation of BM cells from GFP + green mice to senescence-accelerated mouse prone 10 (SAMP10) mice provided direct evidence that BM-derived MuSCs also contribute to aged muscle regeneration (unpublished data), suggesting that the beneficial muscle effects of rPLF-1 are likely attributable, at least in part, to amelioration of BM-derived muscle stem cell regeneration capacity and muscle dysfunction in our experimental model.…”

Section: Discussionmentioning

confidence: 99%

Proliferin-1 Ameliorates Cardiotoxin-Related Skeletal Muscle Repair in Mice

Goto

Inoue

Piao

et al. 2021

Stem Cells International

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Background. We recently demonstrated that proliferin-1 (PLF-1) functions as an apoptotic cell-derived growth factor and plays an important role in vascular pathobiology. We therefore investigated its role in muscle regeneration in response to cardiotoxin injury. Methods and Results. To determine the effects of PLF-1 on muscle regeneration, we used a CTX-induced skeletal muscle injury model in 9-week-old male mice that were administered with the recombinant PLF-1 (rPLF-1) or neutralizing PLF-1 antibody. The injured muscles exhibited increased levels of PLF-1 gene expression in a time-dependent manner. On day 14 after injury, rPLF-1 supplementation ameliorated CTX-induced alterations in muscle fiber size, interstitial fibrosis, muscle regeneration capacity, and muscle performance. On day 3 postinjury, rPLF-1 increased the levels of proteins or genes for p-Akt, p-mTOR, p-GSK3α/β, p-Erk1/2, p-p38MAPK, interleukin-10, Pax7, MyoD, and Cyclin B1, and it increased the numbers of CD34+/integrin-α7+ muscle stem cells and proliferating cells in the muscles and/or bone marrow of CTX mice. An enzyme-linked immunosorbent assay revealed that rPLF-1 suppressed the levels of plasma tumor necrosis factor-α and interleukin-1β in CTX mice. PLF-1 blocking accelerated CTX-related muscle damage and dysfunction. In C2C12 myoblasts, rPLF-1 increased the levels of proteins for p-Akt, p-mTOR, p-GSK3α/β, p-Erk1/2, and p-p38MAPK as well as cellular functions; and these effects were diminished by the depletion of PLF-1 or silencing of its mannose-6-phosphate receptor. Conclusions. These findings demonstrated that PLF-1 can improve skeletal muscle repair in response to injury, possibly via the modulation of inflammation and proliferation and regeneration, suggesting a novel therapeutic strategy for the management of skeletal muscle diseases.

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Hypoxia preconditioned bone marrow-derived mesenchymal stromal/stem cells enhance myoblast fusion and skeletal muscle regeneration

Cited by 35 publications

References 106 publications

Hypoxia: molecular pathophysiological mechanisms in human diseases

Hypoxia: molecular pathophysiological mechanisms in human diseases

The miR151 and miR5100 Transfected Bone Marrow Stromal Cells Increase Myoblast Fusion in IGFBP2 Dependent Manner

Proliferin-1 Ameliorates Cardiotoxin-Related Skeletal Muscle Repair in Mice

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