Human adipose‐derived stem cells attenuate cigarette smoke induced bone marrow hypoplasia via secretion of anti‐inflammatory cytokine TSG‐6

Abstract

IntroductionWe have previously observed bone marrow hypoplasia in a murine model of chronic smoking, which was ameliorated by murine adipose‐derived stromal cells (ASC). This study was designed to test the hypothesis that ASC exert their marrow protective effects through key paracrine factors.MethodsMice (NSG) were exposed to cigarette smoke (CS) for 1 day to 6 months. Human ASC or ASC conditioned media were administered through intravenous (i.v.) or intraperitoneal (i.p.) injections. Expression of TSG‐6 in ASC were knocked down by siRNA and confirmed by real‐time PCR and ELISA. BM hematopoietic progenitor subsets were quantified by colony forming‐unit assays. Possible engrafted human ASC in mouse BM were examined by anti‐human nuclei staining.ResultsCS (6 mos) significantly reduced BM hematopoietic progenitors (vs. nonsmoker, 50.7%, p<0.01), which was restored by human ASC i.p. (110.6%, p>0.05) and i.v. (70.9%; p>0.05). Such damage occurred acutely after one‐day exposure (61.6 %, p<0.01), and could be ameliorated with either ASC (111.0%, p>0.05) or ASC conditioned media (105.7%, p>0.05). Knocking down TSG‐6 (>90%) abolished the protective effect of ASC. No human cells were detected in recipient mouse bone marrow.ConclusionsThe protective effects of ASC against smoking‐induced myelosuppression are mediated by paracrine factor TSG‐6 rather than cell engraftment or differentiation.Research supported by American Heart Association