Enhanced migration and immunoregulatory capacity of BMSCs mediated by overexpression of CXCR4 and IL-35

Mol Immunol. 2022 Oct:150:1-8. doi: 10.1016/j.molimm.2022.07.005. Epub 2022 Jul 28.

Abstract

Bone marrow-derived mesenchymal stem cells (BMSCs) have been widely studied for their applications in immunoregulation and tissue repair. However, the therapeutic effects of BMSCs in the body are limited, partly due to the low homing efficiency of BMSCs to affected parts. The stromal cell-derived factor 1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) axis is well known to play an essential role in the homing of BMSCs. Interleukin 35 (IL-35) is a newly discovered cytokine confirmed to inhibit overactivated immune function and have a good therapeutic effect on autoimmune diseases. In this study, we innovatively developed dual gene modification of BMSCs by transducing CXCR4 and IL-35 and found that the migration and immunomodulatory activity of genetically engineered BMSCs were significantly enhanced compared to their natural counterparts. These results suggest that BMSCs modified by dual overexpression of CXCR4 and IL-35 may provide a potential treatment strategy for autoimmune diseases.

Keywords: BMSCs; CXCR4; Homing; IL-35; Immunoregulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmune Diseases*
  • Bone Marrow Cells
  • Cell Movement / genetics
  • Chemokine CXCL12
  • Humans
  • Immunity
  • Interleukins / pharmacology
  • Mesenchymal Stem Cell Transplantation* / methods
  • Receptors, CXCR4 / genetics
  • Stem Cells

Substances

  • CXCR4 protein, human
  • Chemokine CXCL12
  • Interleukins
  • Receptors, CXCR4