Effects of Human Adipose-Tissue Derived Stem Cell Infusion on the Immunological Consequences in Skin Allograft Mice / 대한이식학회지

ABSTRACT

BACKGROUND: Many in vitro experiments have demonstrated the immunosuppressive properties of mesenchymal stem cells (MSCs). However, such properties have not yet been fully established in an in vivo setting. The purpose of this study was to determine immunosuppressive and anti-inflammatory properties of MSCs in a preclinical animal model in order to pave the way for replacement of conventional immunosuppressive therapy. METHODS: Male C57BL/6 mice and male BALB/c mice were chosen as skin graft donors and recipients, respectively. After performance of full-thickness skin transplantation on the back of mice, adipose tissue derived stem cells (1.0x10(6)/0.1 mL) stained with 4, 6-diamidino-2-phenylindole were transplanted into adipose tissue derived stem cell (ASC)-infused mice and phosphate buffered saline (PBS; 0.1 mL) was infused into PBS-infused mice. Immunological properties and graft survival were accessed and compared. RESULTS: The serum levels of proinflammatory interleukin (IL)-6 showed a decrease in ASC-infused mice compared to PBS-infused mice (P<0.005). In addition, interferon-lambda, IL-10, and tumor necrosis factor-alpha mRNA levels in the skin graft showed a decrease in ASC-infused mice, although without statistical significance. In ASC-infused mice, donor specific hyporesponsiveness was identified in a mixed lymphocyte reaction assay at 30 days after transplantation. In addition, ASC-infusion resulted in markedly prolonged skin allograft survival compared with PBS-infusion (P<0.001). CONCLUSIONS: Administration of ASC not only induced anti-inflammation and immunosuppression, but also resulted in prolonged graft survival, suggestive of their potent immunosuppressive properties. Therefore, conduct of further and more exquisite studies will be required in order to determine the role of MSC in the solid organ transplantation field in order to avoid adverse effects and toxicities caused by chemical immunosuppressive regimens.