Abstract
BackgroundBone marrow mesenchymal stem cells (BMMSCs) have shown immunosuppressive activity in transplantation. This study was designed to determine whether BMMSCs could improve outcomes of small bowel transplantation in rats.MethodsHeterotopic small bowel transplantation was performed from Brown Norway to Lewis rats, followed by infusion of BMMSCs through the superficial dorsal veins of the penis. Controls included rats infused with normal saline (allogeneic control), isogeneically transplanted rats (BN-BN) and nontransplanted animals. The animals were sacrificed after 1, 5, 7 or 10 days. Small bowel histology and apoptosis, cytokine concentrations in serum and intestinal grafts, and numbers of T regulatory (Treg) cells were assessed at each time point.ResultsAcute cellular rejection occurred soon after transplantation and became aggravated over time in the allogeneic control rats, with increase in apoptosis, inflammatory response, and T helper (Th)1/Th2 and Th17/Treg-related cytokines. BMMSCs significantly attenuated acute cellular rejection, reduced apoptosis and suppressed the concentrations of interleukin (IL)-2, IL-6, IL-17, IL-23, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ while upregulating IL-10 and transforming growth factor (TGF)-β expression and increasing Treg levels.ConclusionBMMSCs improve the outcomes of allogeneic small bowel transplantation by attenuating the inflammatory response and acute cellular rejection. Treatment with BMMSCs may overcome acute cellular rejection in small bowel transplantation.
Highlights
Small bowel transplantation (SBTx) is the sole life-saving treatment for patients with intestinal failure who fail total parenteral nutrition (TPN) or who develop irreversible liver failure due to TPN [1]
The cells isolated from rat bone marrow were confirmed as being Bone marrow mesenchymal stem cells (BMMSCs) based on their spindle-shaped morphology, adherence to plastic and ability to differentiate into chondrocytes, adipocytes, osteocytes, and hepatocytes in vitro doi:10.1371/journal.pone.0114528.g001
Flow cytometry showed that the BMMSCs preparations were .95% pure, and that .98% of these cells were positive for CD29, CD90 and RT1A and negative for CD34, CD45 and RT1B (Fig. 1)
Summary
Small bowel transplantation (SBTx) is the sole life-saving treatment for patients with intestinal failure who fail total parenteral nutrition (TPN) or who develop irreversible liver failure due to TPN [1]. This study was designed to determine whether BMMSCs could improve outcomes of small bowel transplantation in rats. Small bowel histology and apoptosis, cytokine concentrations in serum and intestinal grafts, and numbers of T regulatory (Treg) cells were assessed at each time point. Results: Acute cellular rejection occurred soon after transplantation and became aggravated over time in the allogeneic control rats, with increase in apoptosis, inflammatory response, and T helper (Th)1/Th2 and Th17/Treg-related cytokines. BMMSCs significantly attenuated acute cellular rejection, reduced apoptosis and suppressed the concentrations of interleukin (IL)-2, IL-6, IL-17, IL-23, tumor necrosis factor (TNF)-a, and interferon (IFN)-c while upregulating IL-10 and transforming growth factor (TGF)-b expression and increasing Treg levels. Conclusion: BMMSCs improve the outcomes of allogeneic small bowel transplantation by attenuating the inflammatory response and acute cellular rejection. Treatment with BMMSCs may overcome acute cellular rejection in small bowel transplantation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
