Human umbilical cord mesenchymal stem cells-derived exosomes for treating traumatic pancreatitis in rats

Background: The therapeutic and protective efects of human umbilical cord mesenchymal stem cells-exosomes (hucMSC-Exs) on traumatic pancreatitis (TP) remain unknown. Here, we established a rat model of TP and evaluated and compared the therapeutic efects of hucMSC-Exs. Methods: HucMSC-Exs were obtained by ultracentrifugation and identifed using transmission electron microscopy and western blot analysis. TP rats were treated by tail vein injection of hUC-MSCs and hucMSC-Exs. Their homing in rats was observed by performing fuorescence microscopy. Rat pancreatic tissue was subjected to high-throughput sequence to determine transcriptome expression levels. The degree of pancreatic tissue damage was assessed by HE staining, the expression levels of amylase, lipase, and infammatory cytokines were detected by ELISA, apoptosis was detected by TUNEL assay, and the expression levels of various apoptosis-related proteins were detected by western-blot. The expression levels of apoptosis-related molecular markers were detected by RT-qPCR. Results: The colonization of exosomes was observed in pancreatic tissue. Compared to TP group, the histopathological score of pancreas was signifcantly decreased in the TP+hucMSC-Exs group (P<0.05). Compared to TP group, the activity of serum amylase and lipase was signifcantly decreased (P<0.05). The expression levels of IL-6 and TNF-α were signifcantly decreased, while those of IL-10 and TGF-β were signifcantly increased (P<0.05). The apoptosis index of the TP group was signifcantly increased (P<0.05), whereas that of the TP+hucMSC-Exs groups was signifcantly decreased (P<0.05). Compared to TP group, the expression levels of Bax, Bcl-2, and Caspase-3 were signifcantly decreased in the TP+hUC-MSCs group and TP+hucMSC-Exs group (P<0.05). Conclusion: HucMSC-Exs can colonize injured pancreatic tissue, inhibit the apoptosis of acinar cells, and control the systemic infammatory response to facilitate the repair of pancreatic tissue. Six SD rats were randomly divided into three groups, namely the control group (Control group), TP group, and human umbilical cord mesenchymal stem cells-Exosomes group (TP+hucMSC-Exs group). In the control group, rats were fxed after anesthesia and laparotomy was performed. The pancreas was gently turned over several times with sterile cotton swabs and then closed. Approximately 1 ml normal saline was injected via the tail veins of rats. In the TP group, rats were anesthetized and fxed as mentioned above and pancreatic tissues were gently isolated. An animal model of TP was established via controlling the injury area using a self-developed multifunctional impactor. Pancreatic tissue was percussed and squeezed at extrusion parameters of 3 cm2/10 kg. Similarly, approximately 1 ml normal saline was injected via the tail veins of rats in the TP+hUC-MSCs group, and a TP model was established for this group. hUC-MSCs (1× 10^5/100 g) were injected via the tail veins of rats in the TP+hUCMSCs group, and a TP model was established for this group. hucMSC-Exs (10 μg/100 g) were injected via the tail veins of rats in the TP+hucMSC-Exs group (Fig. 1). All rats were sacrificed after 24 h of modeling, and pancreatic tissue were retained for subsequent experiments. The multifunctional animal impact equipment has been authorized patent (self-developed, patent number: ZL 2016 1 0347341.5). hUC-MSCs were provided by the Chengdu KangErmei Biological Cell Preparation Center (Number: G01210001).