Understanding the Molecular Mechanisms of Early Postnatal Development of Pig Islets

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Very few studies in rodents have investigated the development of islets after birth and none so far has examined the development of pig islets during postnatal period in particular, the role of cell adhesion molecules, cadherins in this process. Thus, novel findings from my NSERC program will provide a better understanding on the molecules involve in the formation and maintenance of islet architecture as well as normal function of islets after birth. In addition, the vascular endothelial components of pig islets are poorly understood. It has been known for some time that islets from adult pigs are difficult to isolate and maintain in culture due to their fragile nature compared to islets from newborn pigs, which make the latter an attractive source of islets for transplantation. In addition, it has been known for some time that newborn pig islets have the capacity to grow into mature islets. However, the processes involved in the maturation of newborn pig islets remain to be elucidated. I suspect that cadherins may explain in part the differences we observed between newborn and adult pig islets. Since I started working on newborn pig islets the focus of majority of studies in the field has been on developing strategies on how to prevent their rejection. These strategies involved the genetic engineering of pig islet donors among others and their ability to survive and function in large animal models including non-human primates has been proven to be successful. However, these recipients were heavily immunosuppressed and these regimens are very toxic and are not applicable to human patients. As more and more genetically engineered pigs being created worldwide as source of islets for transplantation, the basic biology of pig islets has not been intensively studied. Thus, our understanding of the tissue we hope to use as a possible solution to the shortage of human islets for transplantation has been limited. I believe that understanding the basic biology of pig islets is fundamental in the successful translation of pig islet transplantation to the clinic. I also believe that the more we know about the tissue we are using for transplantation the more we will be able to successfully transplant the tissue without using immunosuppressive drugs. These drugs are harmful to the tissue itself as well as they pose major risk of infection and development of cancer in islet transplant recipients.