The factors present in regenerating muscles impact bone marrow-derived mesenchymal stromal/stem cell fusion with myoblasts

Stem Cell Research & Therapy

Paulina Kasprzycka¹  Maria A. Ciemerych¹  Mariusz Piotrowski¹  Bartosz Mierzejewski¹  Małgorzata Zimowska¹  Władysława Stremińska¹  Magdalena Gołąbek¹  Agata Ryżko¹  Katarzyna Jańczyk-Ilach¹  Aliksandra Irhashava¹  Karolina Archacka¹  Milena Rafałko¹  Kamil Kowalski¹  Iwona Grabowska¹  Kamil Senderowski¹  Edyta Brzoska¹  Anna Fogtman²  Roksana Iwanicka-Nowicka³  Marta Koblowska³  Piotr Walczak⁴  Mirosław Janowski⁴ 

[1] Department of Cytology, Faculty of Biology, University of Warsaw;Laboratory of Microarray Analysis, Institute of Biochemistry and Biophysics, Polish Academy of Sciences;Laboratory of Systems Biology, Faculty of Biology, University of Warsaw;Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine;

关键词: BM-MSC;    Fusion;    IGF-1;    IL-4;    IL-6;    Myogenic differentiation;   

DOI  :  10.1186/s13287-019-1444-1

来源: DOAJ

【 摘 要 】

Abstract Background Satellite cells, a population of unipotent stem cells attached to muscle fibers, determine the excellent regenerative capability of injured skeletal muscles. Myogenic potential is also exhibited by other cell populations, which exist in the skeletal muscles or come from other niches. Mesenchymal stromal/stem cells inhabiting the bone marrow do not spontaneously differentiate into muscle cells, but there is some evidence that they are capable to follow the myogenic program and/or fuse with myoblasts. Methods In the present study we analyzed whether IGF-1, IL-4, IL-6, and SDF-1 could impact human and porcine bone marrow-derived mesenchymal stromal/stem cells (hBM-MSCs and pBM-MSCs) and induce expression of myogenic regulatory factors, skeletal muscle-specific structural, and adhesion proteins. Moreover, we investigated whether these factors could induce both types of BM-MSCs to fuse with myoblasts. IGF-1, IL-4, IL-6, and SDF-1 were selected on the basis of their role in embryonic myogenesis as well as skeletal muscle regeneration. Results We found that hBM-MSCs and pBM-MSCs cultured in vitro in the presence of IGF-1, IL-4, IL-6, or SDF-1 did not upregulate myogenic regulatory factors. Consequently, we confirmed the lack of their naïve myogenic potential. However, we noticed that IL-4 and IL-6 impacted proliferation and IL-4, IL-6, and SDF-1 improved migration of hBM-MSCs. IL-4 treatment resulted in the significant increase in the level of mRNA encoding CD9, NCAM, VCAM, and m-cadherin, i.e., proteins engaged in cell fusion during myotube formation. Additionally, the CD9 expression level was also driven by IGF-1 treatment. Furthermore, the pre-treatment of hBM-MSCs either with IGF-1, IL-4, or SDF-1 and treatment of pBM-MSCs either with IGF-1 or IL-4 increased the efficacy of hybrid myotube formation between these cells and C2C12 myoblasts. Conclusions To conclude, our study revealed that treatment with IGF-1, IL-4, IL-6, or SDF-1 affects BM-MSC interaction with myoblasts; however, it does not directly promote myogenic differentiation of these cells.

【 授权许可】

Unknown