Biological and biomaterial approaches for improved islet transplantation.
Islet transplantation may be used to treat type I diabetes. Despite tremendous progress in islet isolation, culture, and preservation, the clinical use of this modality of treatment is limited due to post-transplantation challenges to the islets such as the failure to revascularize and immune destruction of the islet graft. In addition, the need for lifelong strong immunosuppressing agents restricts the use of this option to a limited subset of patients, which is further restricted by the unmet need for large numbers of islets. Inadequate islet supply issues are being addressed by regeneration therapy and xenotransplantation. Various strategies are being tried to prevent beta-cell death, including immunoisolation using semipermeable biocompatible polymeric capsules and induction of immune tolerance. Genetic modification of islets promises to complement all these strategies toward the success of islet transplantation. Furthermore, synergistic application of more than one strategy is required for improving the success of islet transplantation. This review will critically address various insights developed in each individual strategy and for multipronged approaches, which will be helpful in achieving better outcomes.
Narang
Ajit S
AS
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 26 S. Dunlap St., Feurt Building, Room 413, Memphis, TN 38163, USA.
Mahato
Ram I
RI
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery*; D018014:Gene Transfer Techniques; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D007515:Islets of Langerhans / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000379:methods; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D007166:Immunosuppressive Agents; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A