The Influence of Inflammation on the Characteristics of Adipose-derived Mesenchymal Stem Cells (ADMSCs)

Abstract Background: Mesenchymal stem cells (MSCs) are adult stem cells with self-renewal and multi-directional differentiation potential, and possess the functions of immunomodulation, regulation of cell growth, and repair of damage. Over recent years, MSCs have been found to regulate the secretion of inflammatory factors and to exert regulatory effects on various lymphocytes in inflammatory states, and on the subsequent repair of tissue damage caused by inflammation. In the present study, we analyzed the effects of tissue inflammation on the characteristics ofMSCs. Methods: Human fat derived from the infrapatellar fat pad (IPFP) of knees with differing degrees of inflammation were extracted from specimens derived from total knee arthroplasties. HE and immunohistochemical staining was performed to directly observe the evidence and degree of inflammation in human infrapatellar fat pad tissue in order to classify MSCs cells, by their origin, into highly inflamed and lowly inflamed groups, and to study the effect of tissue inflammation on cell acquisition rates via cellular counting data. Flow cytometry assays were performed to investigate the effect of tissue inflammation on MSC surface marker expression. Trilineage differentiation, including osteogenesis, adipogenesis, and chondrogenesis was performed to assess the effect of tissue inflammation on the ability of MSCs to undergo directed differentiation. The effect of tissue inflammation on the ability of MSCs to proliferate was investigated via clone formation studies. RNA-sequencing was performed to evaluate the transcriptomes of MSCs derived from different areas of inflammation. The effect of tissue inflammation on tissue repair capacity and safety of MSCs were investigated via a murine model of acute liver injury. Results: The results of cell count data indicate that a high degree of tissue inflammation significantly decreases the acquisition rate of MSCs, and the proportion of CD34+ and CD146+ cells. The results of our trilineage differentiation assay shows that a higher degree of inflammation decreases osteogenic differentiation, and enhances adipogenic and chondrogenic differentiation of MSCs. Clone formation assays indicates that a higher degree of tissue inflammation at the MSC source increases the proliferative ability of MSCs. The transcriptomes of MSCs remain relatively stable in fat pad tissues derived from both highly and lowly inflamed samples. The results of acute liver injury investigations in mice indicate that MSCs of low inflammatory tissue origin have an enhanced tissue repair capability. Conclusions: High tissue inflammation at the source of MSCs reduces the acquisition rate of MSCs, increases the proliferative capacity of MSCs, inhibits osteogenic differentiation, and enhances adipogenic and chondrogenic differentiation. A higher degree of tissue inflammation reduces the tissue repair capacity of MSCs; however, MSCs obtained from differing source degrees of inflammation retain stable and similar genetic transcriptomic information, and have good tissue repair capability.