Mesenchymal Stem Cells from Mouse Hair Follicles Inhibit the Development of Type 1 Diabetes

Abstract

Mesenchymal stem cells (MSCs) are known for their immunosuppressive properties. Based on the demonstrated anti-inflammatory effect of mouse MSCs from hair follicles (moMSCORS) in a murine wound closure model, this study evaluates their potential for preventing type 1 diabetes (T1D) in C57BL/6 mice. T1D was induced in C57BL/6 mice by repeated low doses of streptozotocin. moMSCORS were injected intravenously on weekly basis. moMSCORS reduced T1D incidence, the insulitis stage, and preserved insulin production in treated animals. moMSCORS primarily exerted immunomodulatory effects by inhibiting CD4+ T cell proliferation and activation. Ex vivo analysis indicated that moMSCORS modified the cellular immune profile within pancreatic lymph nodes and pancreatic infiltrates by reducing the numbers of M1 pro-inflammatory macrophages and T helper 17 cells and upscaling the immunosuppressive T regulatory cells. The proportion of pathogenic insulin-specific CD4+ T cells was down-scaled in the lymph nodes, likely via soluble factors. The moMSCORS detected in the pancreatic infiltrates of treated mice presumably exerted the observed suppressive effect on CD4+ through direct contact. moMSCORS alleviated T1D symptoms in the mouse, qualifying as a candidate for therapeutic products by multiple advantages: non-invasive sampling by epilation, easy access, permanent availability, scalability, and benefits of auto-transplantation.

Keywords

• MSC therapy
• autoimmunity
• immunomodulation
• streptozotocin
• mouse model
• insulin expression