Bioengineered omental transplant site promotes pancreatic islet allografts survival in non-human primates
Hongping Deng, Alexander Zhang, Dillon Ren Rong Pang, Yinsheng Xi, Zhihong Yang, Rudy Matheson, Guoping Li, Hao Luo, Kang M. Lee, Qiang Fu, Zhongliang Zou, Tao Chen, Zhenjuan Wang, Ivy A. Rosales, Cole W. Peters, Jibing Yang, María M. Coronel, Esma S. Yolcu, Haval Shirwan, Andrés J. Garcı́a, James F. Markmann, Ji Lei
Abstract
The transplanting islets to the liver approach suffers from an immediate posttransplant loss of islets of more than 50%, progressive graft dysfunction over time, and precludes recovery of grafts should there be serious complications such as the development of teratomas with grafts that are stem cell-derived islets (SC-islets). The omentum features an attractive extrahepatic alternative site for clinical islet transplantation. We explore an approach in which allogeneic islets are transplanted onto the omentum, which is bioengineered with a plasma-thrombin biodegradable matrix in three diabetic non-human primates (NHPs). Within 1 week posttransplant, each transplanted NHP achieves normoglycemia and insulin independence and remains stable until termination of the experiment. Success was achieved in each case with islets recovered from a single NHP donor. Histology demonstrates robust revascularization and reinnervation of the graft. This preclinical study can inform the development of strategies for β cell replacement including the use of SC-islets or other types of novel cells in clinical settings.