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Engraftment, function and beta cell regulation in the adrenal transplant model

Subject Area Endocrinology, Diabetology, Metabolism
Term from 2011 to 2018
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 189897882
 
Diabetes mellitus represents a major threat being the only non-infective disease reaching epidemic dimensions. Although enormous effort is made in developing prevention programmes and increasingly effective pharmacological means for diabetes exist, they do not adequately protect from its numerous and severe complications and the need of new strategies for diabetes therapy is urgent. Currently, pancreata and isolated islets represent the only means to supply new beta cells to type 1 diabetes patients. However, the long-term outcome of islet transplantation is still unsatisfactory. A major limiting factor for long-term function of islet transplants is the inappropriate microenvironment after intraportal transplantation and proper islet function is highly dependent upon special niche and/or differentiating factors. Within this study we aim to evaluate the microenvironment of the adrenal as a potentially favourable transplantation site that promotes beta cell engraftment, survival, proliferation and long-term function. During the first funding period we could already demonstrate in a newly developed islet-adrenal co-culture model the beneficial effect of this endocrine alliance on islet viability and secretory capacity. Furthermore, a novel small animal model of intra-adrenal islet transplantation showed the superiority of this site compared to traditional transplant models. Based upon these promising results, the hypothesis of the two endocrine systems of pancreatic islets and the adrenal being a beneficial alliance will be studied in a large animal pre-clinical model. We believe that this approach using the adrenal microenvironment as a privileged site for islet transplantation may eventually be translated to human application as a novel treatment strategy.
DFG Programme Clinical Research Units
 
 

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