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Despite clear progress made during the last 15 years on cellular transplantation for T1D, the most recent results demonstrate a long-term limited viability of engrafted islets and, as a result, limited insulin independence under different novel modalities of immunosuppressive (IS) regimens tested. In addition, even the most innovative IS regimens required for transplant survival still have significant immediate side effects and long-term safety is uncertain. These problems together with the scarcity of donor organs and the complexity of transplants mandates a renewed emphasis on the investigation of novel methods within the field of tissue engineering for the development of a bio-artificial, cell-based hormone replacement therapy that may minimize the need of IS. To support this, it is necessary to develop/optimize novel/smart/safe biomaterials, scaffolds, bio-matrices and bio-barriers that may protect grafted cells from immune rejection and simultaneously promote appropriate vascularization/innervation with an efficient exchange of nutrients to optimize cellular long-term survival and proper function. It is also necessary to investigate methods to use different cell sources including human progenitor cells and induced pluripotent stem cells as a valid option for cell replacement therapy. Also, further research on the potential use of xenogeneic cells/islets is needed. Recent advances in this field, because of support by NIDDK/NIH and other funding agencies, demonstrate feasibility of these technologies, mainly in rodent pre-clinical models of T1D. However, important obstacles remain before long-term preclinical efficacy in non-human primates (NHP) and human clinical feasibility may be verified.
For more information, visit: https://grants.nih.gov/grants/guide/rfa-files/RFA-DK-19-028.html
