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

Paulina Kasprzycka, Karolina Archacka, Kamil Kowalski, Bartosz Mierzejewski, Małgorzata Zimowska, Iwona Grabowska, Mariusz Piotrowski, Milena Rafałko, Agata Ryżko, Aliksandra Irhashava, Kamil Senderowski, Magdalena Gołabek, Władysława Stremińska, Katarzyna Jańczyk-Ilach, Marta Koblowska, Roksana Iwanicka-Nowicka, Anna Fogtman, Mirosław Janowski, Piotr Walczak, Maria A. CiemerychEdyta Brzoska

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number343
JournalStem Cell Research and Therapy
Volume10
Issue number1
DOIs
StatePublished - Nov 21 2019

Keywords

  • BM-MSC
  • Fusion
  • IGF-1
  • IL-4
  • IL-6
  • Myogenic differentiation
  • SDF-1

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Cell Biology

Fingerprint

Dive into the research topics of 'The factors present in regenerating muscles impact bone marrow-derived mesenchymal stromal/stem cell fusion with myoblasts'. Together they form a unique fingerprint.

Cite this