Transplantation of mesenchymal stem cells into the skeletal muscle induces cytokine generation

Cytokine. 2013 Oct;64(1):243-50. doi: 10.1016/j.cyto.2013.06.314. Epub 2013 Jul 13.

Abstract

Mesenchymal stem cells due to the high proliferative potential, capacity of multilineage differentiation became a hope of regenerative medicine. However, the organism's response to the transplantation of MSCs is not fully elucidated. The aim of the present study was to evaluate the acute local tissue response to syngeneic MSCs administration into the muscle. Rat syngeneic MSCs were transplanted into the skeletal muscle and the tissue surrounding the injection site was collected after 24h. Analogous samples from untreated and PBS treated muscles served as controls. The analysis of genes expression using real-time PCR revealed significant up-regulation of proinflammatory cytokines: IL-1α, IL-1β, IL-6 in MSCs treated muscles in comparison to the PBS group. The evaluation of protein concentration (ELISA) in collected samples showed that injection of MSCs caused significant elevation of IL-1β. Immunofluorescent assessment of the tissue revealed infiltration of leukocytes and macrophages. Quantitative analysis of the samples immunostained for CD68 and CD43 antigens revealed that the number of phagocytes was significantly higher in MSC treated muscle when compared to the samples from PBS group. To conclude, the administration of mesenchymal stem cells into the muscle in syngeneic model induces the features of acute inflammation that affects cell engraftment.

Keywords: Cytokines; Inflammation; Mesenchymal stem cells; Transplantation.

MeSH terms

  • Adipogenesis / physiology
  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Cell Differentiation
  • Inflammation / immunology
  • Interleukin-1alpha / biosynthesis*
  • Interleukin-1alpha / metabolism
  • Interleukin-1beta / biosynthesis*
  • Interleukin-1beta / metabolism
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / metabolism
  • Leukocyte Count
  • Leukocytes / cytology
  • Leukosialin / metabolism
  • Macrophages / cytology
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / metabolism*
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism
  • Osteogenesis / physiology
  • Rats
  • Rats, Inbred Lew
  • Up-Regulation

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 protein, rat
  • Interleukin-1alpha
  • Interleukin-1beta
  • Interleukin-6
  • Leukosialin