The SDF-1/CXCR4 axis regulates migration of transplanted bone marrow mesenchymal stem cells towards the pancreas in rats with acute pancreatitis

Abstract

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.

Experimental Study on Bone Marrow Mesenchymal Stem Cells for the Treatment of Acute Pancreatitis in Rats

“…The bone marrow derived MSCs were injected into SAP rats via the tail vein, intraperitoneal or tail vein+intraperitoneal respectively. Some studies showed that MSCs could migrate into pancreas during early phase in AP [16,17]. Consistent with recent studies, bmMSCs presented in pancreas on days 1, 2 and 3 when we injected bmMSCs through tail vein or through tail vein + intraperitoneal.…”

“…To date, accumulated evidence from preclinical and linical studies has confirmed that MSCs conferred biological and functional protections in diabetes, myocardium infarction, brain and spinal cord injury etc [15]. In re-sent years some experiment have reported the protective roles of MSCs in AP [16][17][18][19][20] MSCs infusion through tail vein can protect the structural integration of acinar cells, promoted pancreatic angiogenesis, significantly inhibited inflammation and attenuate acinar cell apoptosis. Sun XC found that intraperitoneal injection of MSCs exerted protective effects on pancreas and small intestine injury [21].…”

Effect of Fetal Membrane-Derived Mesenchymal Stem Cell Transplantation in Rats With Acute and Chronic Pancreatitis

“…32,33 Recently, therapeutic effects of human MSCs derived from bone marrow and umbilical cord on acute pancreatitis in rats have been reported. 29,34,35 In our study, rat FM-MSCs led to lower histological scoring and suppressed inflammatory cell infiltration in the acute pancreatitis model.…”

Therapeutic effect of human clonal bone marrow-derived mesenchymal stem cells in severe acute pancreatitis

“…However, the specific mechanisms are still poorly understood. Previous studies have shown that MSCs can migrate into the injured pancreas and repair it (Gong et al 2014;Jung et al 2011). Since it is crucial that systemically delivered MSCs reach the site of injury during stem cell therapy, we used CMDiI, a cell tracker, and identified whether CM-DiI-labeled hcMSCs can migrate into the injured pancreas.…”

“…The overall mortality of SAP patients with MODS and infectious pancreatic necrosis is as high as 47 % (Chan and Leung 2007). Current conservative therapies, including inhibition of pancreatic enzyme synthesis and secretion, use of antibiotics, and nutritional support, are frequently utilized as clinical treatment of SAP (Gong et al 2014). However, there are no effective strategies for the treatment of SAP, thus far.…”