Implementation of a Simplified Method of Islet Isolation To Facilitate Allogeneic Islet Transplantation in Cynomolgus Monkeys
Surgery, University of Illinios at Chicago, Chicago, IL
Meeting: 2013 American Transplant Congress
Abstract number: A686
Purpose: Non-human primate (NHP) is considered the optimal pre-clinical model for islet transplantation studies. The present study describes a simple and cost-effective islet isolation procedure. Using this method, allogeneic islets reverse diabetes in cynomolgus monkeys.
Methods: Pancreatic tissue from cynomolgus monkey were digested, collected, and purified using a simplified method, without the usage of Ricordi chamber and Cobe 2991 cell processor. Islet quantification, purity, viability and glucose static incubation were conducted immediately after isolation. Five streptozotocin induced diabetic monkeys were transplanted intrahepatically with the islets harvested from a total of eleven donor monkeys. After transplantation, liver biopsies from three monkeys were taken at different time points for histological study.
Results: The average islet yield was 32,196 ± 13,984 islet equivalent (IEQ)/gland, or 3,669 ± 2,061 IEQ/gram tissue. The viability, purity, and static glucose incubation stimulation index was 94.4% ± 2.3, 92.8%, ± 3.4 and 2.6 ± 1.7, respectively. Following transplantation, monkeys that received an average dose of 19,968 ± 2,273 IEQ/kg (n = 4) achieved prolonged normoglycemia (57-232 days); whereas the single monkey, that received an islet dose of 8,000 IEQ/kg, did not experience diabetes reversal. Immunohistochemical assessment of the liver biopsies taken from Recipient #1 at one week and one month after transplantation revealed an insulin- and glucagon-positive islet graft at one week after transplant, but the presence of degenerated islets (H-E staining) and CD3+ CD11b+ cell infiltration (immunofluorescent staining) at one month after transplant. Assessment of the liver biopsy from recipient #2 revealed an insulin- and glucagon-positive islet graft with minimal peri-islet inflammatory infiltration at 103 days after transplant, but not inside islets. Immunohistochemical evaluation of the liver biopsy from recipient #4 revealed a well-granulated insulin-positive islet graft at 6 months after transplant.
Conclusion: This study demonstrates that cynomolgus monkey islets can be successfully and efficiently harvested using a simple isolation method, with clinically acceptable enzymes. Importantly, when transplanted in an allogeneic model, these islets can restore normoglycemia in diabetic monkeys.
To cite this abstract in AMA style:
Qi M, Wang Y, Formo K, Marchese E, Wang S, McGarrigle J, Bochenek M, Kinzer K, Sanchez P, Davis M, Ahn S, Bartholomew A, Benedetti E, Oberholzer J. Implementation of a Simplified Method of Islet Isolation To Facilitate Allogeneic Islet Transplantation in Cynomolgus Monkeys [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/implementation-of-a-simplified-method-of-islet-isolation-to-facilitate-allogeneic-islet-transplantation-in-cynomolgus-monkeys/. Accessed May 17, 2025.« Back to 2013 American Transplant Congress