Stromal cell-derived factor-1 (SDF-1) and its receptor, CXC chemokine receptor-4 (CXCR4), are important regulators in the migration of bone marrow mesenchymal stem cells (BMSCs). However, the mechanisms underlying this effect in acute pancreatitis (AP) have not been investigated. In this study, BMSCs were identified by specific cell surface markers and differentiation potentials, and labeled with chloromethylbenzamido-1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (CM-Dil) for in vivo cell tracking. AP was induced by retrograde infusion of sodium taurocholate into the common bile duct in rats. The expression of SDF-1 in the injured pancreas was determined by immunohistochemistry and western blot analysis. BMSCs were incubated with or without anti-CXCR4 antibody and the contribution of SDF-1 to the migration of BMSCs was investigated. Our results demonstrated that the expression of SDF-1 was significantly increased in the injured pancreas, and that these levels peaked on days 5–7 and began to decrease on day 10. SDF-1 induced a dose-dependent migration of BMSCs in an in vitro transwell migration assay, which was almost completely blocked by AMD3100 (CXCR4-specific antagonist) or anti-CXCR4 antibody. In addition, by encouraging the migration of CM-Dil-labeled BMSCs, the SDF-1/CXCR4 axis facilitated the repair of the injured pancreas. This effect was inhibited by the anti-CXCR4 antibody. Taken together, these results indicate that the interaction of locally produced SDF-1 with CXCR4 on BMSCs, has an important regulatory role in the migration of BMSCs towards the injured pancreas in AP.
We have identified the most appropriate method of isolating human umbilical cord matrix-derived mesenchymal stem cells (UCM-MSCs) and compared morphological, phenotypic, proliferative, and differentiation characteristics of UCM-MSCs with bone marrow-derived MSCs (BM-MSCs) and umbilical cord blood-derived MSCs (UCB-MSCs). Three explant culture methods and 3 enzymatic methods were compared with regards to time for primary culture, cell number, cell morphology, immune phenotype, and differentiation potential. Morphological, phenotypic, proliferative, and differentiation characteristics of UCM-MSCs, BM-MSCs, and UCB-MSCs were also compared. UCM-MSCs isolated using the 10 mm size tissue explant method led to shorter primary culture time, higher numbers of isolated cells, and higher proliferation rates compared with other isolation methods. Immune phenotype and multilineage differentiation capacity did not differ significantly among 6 groups. UCM-MSCs had similar characteristics as BM-MSCs and UCB-MSCs, including fibroblastic morphology, typical immunophenotypic markers, and multilineage differentiation capacity. In comparison with UCB-MSCs and BM-MSCs, UCM-MSCs have higher proliferative capacity, higher rate of chondrogenic differentiation, and higher expression of CD 146. The results suggest that the 10 mm size tissue culture method is the optimal protocol for the isolation of UCM-MSCs. Given the distinct advantages of UC, such as accessibility, painless acquisition, and abundance of cells obtained, we propose that UC be considered an alternative to BM and UCB as a source of MSCs for cell therapy.
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