Systemic infusion of bone marrow-derived mesenchymal stem cells for treatment of experimental colitis in mice
Xiao-Wen He1, Xiao-Sheng He, Lei Lian
1Department of Colorectal and Anal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Rd, Guangzhou, 510655, Guangdong Province, People's Republic of China. hexiaowen7003@126.com
Background And Aims:
The anti-inflammatory and reparative properties of mesenchymal stem cells (MSCs) make them a promising tool for treating immune-mediated and inflammatory disorders. However, whether MSCs can be used for treatment of inflammatory bowel disease (IBD) still remains unclear. In this study, a dextran sulfate sodium (DSS)-induced mouse colitis model was used to test the hypothesis that infused bone marrow-derived MSCs could exert anti-inflammatory effects against experimental colitis.
Methods:
DSS-induced colitis mice were injected with 1 × 10(6) MSCs [in phosphate-buffered saline (PBS)] via the tail vein. Control colitis mice received PBS alone. To trace the injected cells in vivo, MSCs were labeled with chloromethyl-benzamidodialkylcarbocyanine (CM-DiI). On day 15 of the experiment, the colon was sectioned and examined for histopathological changes. Pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β] in the inflamed colon were analyzed by real-time reverse-transcription polymerase chain reaction (RT-PCR). Serum values of TNF-α in mice were evaluated quantitatively by enzyme-linked immunosorbent assay (ELISA) analysis.
Results:
DSS-induced colitis showed symptoms similar to ulcerative colitis in humans, including body weight loss, bloody diarrhea, mucosal ulceration, and shortening of the colon. Bone marrow-derived MSCs significantly ameliorated the clinical and histopathologic severity of DSS colitis compared with non-MSC control. Pro-inflammatory cytokines in both the inflamed colon (TNF-α, IL-1β) and serum (TNF-α) were downregulated in MSC-treated mice in contrast to control. CM-DiI-labeled MSCs accumulated in inflamed regions of the colon, mainly in the submucosa.
Conclusions:
Systemic infusion of bone marrow-derived MSCs may exert therapeutic efficacy on acute DSS-induced colitis in mice through their anti-inflammatory effects, which demonstrates the feasibility of using bone marrow-derived MSCs to treat IBD.
