The CD45⁺ fraction in murine adipose tissue derived stromal cells harbors immune‐inhibitory inflammatory cells

Abstract

Stromal cells in adipose tissue are useful for repair/regenerative therapy as they harbor a substantial number of mesenchymal stem cells; therefore, freshly isolated autologous uncultured adipose tissue derived stromal cells (u-ADSCs) are useful for regenerative therapy, and obviate the need for mesenchymal stem cells. We evaluated the therapeutic effect of murine u-ADSCs and sorted subsets of u-ADSCs in a concanavalin A (ConA) induced murine model of hepatitis, as well as their characteristics. We found that 10-20% of u-ADSCs expressed the CD45 leukocyte-related antigen. CD68, which is a marker of macrophages (MΦs), was expressed by 50% of CD45 u-ADSCs. About 90% of CD68 CD45 cells expressed CD206 antigen, which is a marker of inhibitory M2-type MΦs. Genes related to M2-type MUs were especially more highly expressed by CD45 CD206 u-ADSCs than by CD45 u-ADSCs. CD45 u-ADSCs inhibited the expression of cytokines/chemokines and suppressed the proliferation of splenocytes stimulated with ConA. We observed that not only whole u-ADSCs, but also the CD45 subset of u-ADSCs ameliorated the ConA-induced hepatitis in mice. In conclusion, we show that freshly isolated murine u-ADSCs were effective against acute hepatitis, and CD45 u-ADSCs acting phenotypically and functionally like M2-type MΦs, contributed to the repair of liver tissue undergoing inflammation.

Adipose tissue‐derived stem cells prevent fibrosis in murine steatohepatitis by suppressing IL‐17‐mediated inflammation

“…Inguinal subcutaneous adipose tissues were obtained from C57BL/6J mice and digested with collagenase I (Worthington Biochemical Corp., Lakewood, NJ, USA) to obtain fresh stromal cells, as described previously. 13,[15][16][17] The cells were expanded in culture with Dulbecco's modified Eagle's medium: nutrient mixture F-12 supplemented with 20% heat-inactivated fetal bovine serum (Life Technologies, Carlsbad, CA, USA). The IMS/N murine immortalized hepatic stellate cell line 18 (a kind gift from Dr. Miura) was cultured in the same medium.…”

Distinct chemotherapy‐associated anti‐cancer immunity by myeloid cells inhibition in murine pancreatic cancer models

“…The qRT‐PCR was performed as previously described with modifications: the reaction was conducted with the cDNA mixed with qPCR MasterMix Plus ® (Eurogentec, Seraing, Belgium) and the following hydrolysed Taqman ® Gene Expression Assay probes: Adam8 , Amica1 , Trem1 , Trem3 , Bnip3 l , Bpgm , Cln3 , Fbxo9 , Fech , Hemgn , Hp , Mmp8 , Mmp9 . Relative expression levels were calculated with Gapdh as a reference gene using the 2 −∆∆Ct method.…”

Human Wharton's jelly-derived mesenchymal stem cells alleviate concanavalin A-induced fulminant hepatitis by repressing NF-κB signaling and glycolysis

“…Concanavalin A (Con A)-induced fulminant liver injury is a well-documented murine model closely resembling the pathological process of human viral hepatitis and autoimmune liver disease [20][21][22][23]. Previous studies showed that bone marrow-derived MSCs [19,[24][25][26][27][28][29][30], tonsil-derived MSCs [31], and adipose tissue-derived MSCs [32][33][34][35] effectively protect mice from Con A-induced liver injury. However, the source of MSCs in all these tissues is quite limited, and isolating MSCs from these tissues is invasive.…”