Role of Interleukin-10 Overexpressing Mesenchymal Stem Cells in Promoting Bone Marrow Functional Recovery in Aplastic...

Mesenchymal stem cells (MSCs) are multipotent, nonhematopoietic progenitors capable of supporting hematopoiesis and regulating immunity. Clinical studies have shown that MSCs can aid hematopoietic recovery and balance T helper 17 (Th17) and Treg cells in some aplastic anemia (AA) patients refractory to immunosuppressive therapy (IST). However, full clinical efficacy remains unachieved. To enhance MSC immune regulation while ensuring safety, previous research found interleukin-10 (IL-10), an immunosuppressive factor, can boost MSC function. In this study, we used lentiviral transduction to induce IL-10 gene overexpression in human umbilical cord-derived MSCs and validated their efficacy and safety in AA mouse models.

MSCs were isolated from umbilical cords and genetically modified via lentiviral transduction to overexpress IL-10, generating OEIL10-MSCs. Empty vector plasmids (pCDH-CMV-MCS-EF1-copGFP) were transduced into MSC to create PCDH-MSCs. Both in vitro and in vivo experiments were conducted to investigate their functional changes and mechanisms. Mouse models of nonsevere AA (NSAA) and severe AA (SAA) were established and treated with OEIL10-MSCs or control PCDH-MSCs. The therapeutic efficacy of OEIL10-MSCs in AA was evaluated by assessing blood cell counts, Th17/Treg ratios, and bone marrow histopathology in an AA mouse model. Safety was assessed through liver and kidney function tests.

In vitro experiments verified that OEIL10-MSCs exhibited enhanced proliferation capacity, improved anti-inflammatory ability, and reduced oxidative stress levels. In NSAA mouse models, OEIL10-MSCs were more effective in restoring hematopoietic function and elevating Treg cell proportions. In contrast, in SAA mouse models, OEIL10-MSCs demonstrated superior efficacy in elevating red blood cell (RBC) levels and reducing DNA damage compared to PCDH-MSCs.

Overexpression of IL-10 may enhance the efficacy of MSCs in treating AA, presenting a promising therapeutic strategy for the clinical application of MSCs.