Abstract
BackgroundData available on the immunomodulatory properties of neural stem/precursor cells (NPC) support their possible use as modulators for immune-mediated process. The aim of this study was to define whether NPC administered in combination with pancreatic islets prevents rejection in a fully mismatched allograft model.Methodology/Principal FindingDiabetic Balb/c mice were co-transplanted under the kidney capsule with pancreatic islets and GFP+ NPC from fully mismatched C57BL/6 mice. The following 4 groups of recipients were used: mice receiving islets alone; mice receiving islets alone and treated with standard immunosuppression (IL-2Rα chain mAbs + FK506 + Rapamycin); mice receiving a mixed islet/NPC graft under the same kidney capsule (Co-NPC-Tx); mice receiving the islet graft under the left kidney capsule and the NPC graft under the right kidney capsule (NPC-Tx). Our results demonstrate that only the co-transplantation and co-localization of NPC and islets (Co-NPC-Tx) induce stable long-term graft function in the absence of immunosuppression. This condition is associated with an expansion of CD4+CD25+FoxP3+ T regulatory cells in the spleen. Unfortunately, stable graft function was accompanied by constant and reproducible development of NPC-derived cancer mainly sustained by insulin secretion.ConclusionThese data demonstrate that the use of NPC in combination with islets prevents graft rejection in a fully mismatched model. However, the development of NPC-derived cancer raises serious doubts about the safety of using adult stem cells in combination with insulin-producing cells outside the original microenvironment.
Highlights
Adult multipotent neural stem/precursor cells (NPC) are broadly proposed as an alternative cell source to repair brain damage upon transplantation and NPC-driven brain repair has variably been shown in several pre-clinical models of neurological disorders [1,2]
Diabetic Balb/c mice were transplanted with pancreatic islets (350 EI) and/or NPC (1000 neurospheres, green fluorescent protein (GFP)+) from fully mismatched C57BL/6 mice
In the Islet-Tx group, the allograft was lost at a median survival time (MST) of 1563 days and 16.7% (2/12) of allografts survived without evidence of rejection for 100 days
Summary
Adult multipotent neural stem/precursor cells (NPC) are broadly proposed as an alternative cell source to repair brain damage upon transplantation and NPC-driven brain repair has variably been shown in several pre-clinical models of neurological disorders [1,2]. In vitro NPC directly inhibit T-cell activation and proliferation [3,10,11]. These evidences support the concept that the ‘‘therapeutic plasticity’’ [1] and in particular the immunomodulatory activity is a true functional signature of NPC. Data available on the immunomodulatory properties of neural stem/precursor cells (NPC) support their possible use as modulators for immune-mediated process. The aim of this study was to define whether NPC administered in combination with pancreatic islets prevents rejection in a fully mismatched allograft model
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.
