Immunomodulatory properties of adipose stem cells in vivo: Preclinical and clinical applications

Abstract Adipose stem cells (ASCs) are an appealing cell population for clinical use compared with other stem cell types owing to their ease of harvest, high proliferative capability, genetic stability, potent antiinflammatory and immunosuppressive effects, and ability to evade immune responses. Specifically, ASC immunomodulatory properties have been fervently investigated in multiple applications both in vitro and in vivo. In this chapter, two of the overarching mechanisms used by ASCs to regulate the immune system, direct cell-to-cell contact and paracrine-mediated indirect communication, are discussed. Further, investigations into the use of ASCs to reduce inflammation and induce tolerance in patients undergoing solid organ transplantation or vascularized composite allotransplantation are presented. Numerous preclinical studies and clinical trials focusing on the immunomodulatory effects and their outcomes are also included, which overwhelmingly suggest that ASCs are a therapeutic solution for a wide range of previously untreatable clinical problems, such as inflammatory bowel disease (IBD), graft versus host disease (GvHD), multiple sclerosis (MS), diabetes mellitus, rheumatoid arthritis (RA), or progressive lung disorders. However, the process of obtaining and utilizing ASCs lacks standardization owing to complexity in patient differences, cell isolation and characterization, and regulatory concerns. Understanding the mechanisms through which ASCs receive and respond to information within the microenvironment, especially immune cells, will aid in the standardization of their use and clinical translation.