Improving islet transplantation: a road map for a widespread application for the cure of persons with type I diabetes.
OBJECTIVE
The widespread application of replacement therapies for type I diabetes is at present limited by the side-effects of systemic immunosuppression. Results obtained in several animal models show that islet encapsulation can control the rejection process without systemic side-effects. However, results have, in general, been disappointing when transferred to large animal models or to humans.


RESULTS
Growing insights into how cells respond to mechanical forces and surrounding extracellular matrixes indicate that differences in the Young's modulus (the resistance to deformation) between the implanted biomaterial and surrounding tissues induce inflammation and fibrosis. A valid approach would be to select for implantation a tissue having a higher value of the Young's modulus, for example, bone, allowing direct contact with the highly vascularized bone marrow providing nutrient and oxygen support as well as a rapid distribution of released insulin to the systemic circulation.


CONCLUSIONS
Development of a biochamber with bone-integrating properties will allow initiation of clinical trials with allogeneic human islets, xenogeneic pig islets or insulin-producing cells generated from human embryonic stem cell (hESC)/inducible pluripotent stem cell (iPSC).
Department of Oncology, Radiology & Clinical Immunology, Uppsala University, Sweden. Olle.Korsgren@klinimm.uu.se
Olle
O
Korsgren
Bo
B
Nilsson
D000818:Animals; D001696:Biomechanical Phenomena; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D055119:Elastic Modulus; D053595:Embryonic Stem Cells / Q000637:transplantation; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects / Q000379:methods*; D039904:Pluripotent Stem Cells / Q000637:transplantation; D013552:Swine; D054457:Tissue Scaffolds; D020858:Tissue and Organ Harvesting; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
D007166:Immunosuppressive Agents