2013 - CTS 2013 Congress
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Oral Communications 6
13.1 - Intra BM islet transplantation: modulation of microenvironment to improve engraftment
Presenter: Valeria, Sordi, Milan, Italy
Authors: Valeria Sordi1, Elisa Cantarelli1, Stefania Maniscalco1, Silvia Pellegrini1, Elena Incerti1, Raffaella Melzi1, Lorenzo Piemonti1
Intra BM islet transplantation: modulation of microenvironment to improve engraftment
Valeria Sordi1, Elisa Cantarelli1, Stefania Maniscalco1, Silvia Pellegrini1, Elena Incerti1, Raffaella Melzi1, Lorenzo Piemonti1
1Diabetes Research Institute, San Raffaele Scientific Institute, Milan, Italy
Background. Bone marrow (BM) has been recently proposed as an alternative site for islet transplantation (tx). The BM, for its structure and anatomical position, offers the possibility to modulate microenvironment by local interventions.
Aim.The aim of our study was to investigate whether local irradiation and/or mesenchymal stem cell (MSC) co-tx in mouse are able to improve islet engraftment and prevent rejection in BM.
Methods. A model of BM local irradiation was set up: we established irradiation conditions (932 rad), verified selective cell depletion and chose the time point for tx (3 days after treatment). MSCs from bone marrow (BM-MSCs) or pancreatic tissue (pMSCs) were isolated and characterized for biological and immunomodulatory properties to choose the best candidate for in vivo co-tx. Gain of normoglycaemia and time to rejection were evaluated in a fully MHC mismatched model of intra BM islet tx (400 C57BL/6 IEQ in BALB/c). Islets with or without 300,000 syngeneic MSCs were alternatively infused into irradiated or control femur.
Results. Islet tx into locally irradiated BM had better outcome compared to not irradiated recipients in terms of capacity to gain normoglycaemia (100% vs 55% in irradiated vs not irradiated mice, P=0,069). Glycaemia in the first two weeks after tx was significantly lower in the group of irradiated mice (P=0,047) while time of rejection was not different among the two groups. Pancreatic MSCs showed morphology, phenotype and plasticity comparable to BM-MSC and strong immunomodulatory properties in vitro, resulting the best candidate for co-tx. Preliminary results showed that co-tx of pMSCs and islets in irradiated recipients improved the probability to gain normoglycaemia (100% vs 33% in islets+pMSCs vs islet alone group, respectively) and delays the time of rejection (10,2±4,3 vs 4,0±0 days in islets+pMSCs vs islet alone group, respectively).
Conclusion.Local irradiation of the site of implant and co-tx of pancreas-derived MSCs and pancreatic islets in the BM are promising strategies which can be combined together for the modulation of islet engraftment and survival.
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