Abstract
The most obvious method to observe transplanted islets in the liver is direct biopsy, but the distribution and location of the best biopsy site in the recipient’s liver are poorly understood. Islets transplanted into the whole liver of five diabetic cynomolgus monkeys that underwent insulin-independent survival for an extended period of time after allo-islet transplantation were analyzed for characteristics and distribution tendency. The liver was divided into segments (S1–S8), and immunohistochemistry analysis was performed to estimate the diameter, beta cell area, and islet location. Islets were more distributed in S2 depending on tissue size; however, the number of islets per tissue size was high in S1 and S8. Statistical analysis revealed that the characteristics of islets in S1 and S8 were relatively similar to other segments despite various transplanted islet dosages and survival times. In conclusion, S1, which exhibited high islet density and reflected the overall characteristics of transplanted islets, can be considered to be a reasonable candidate for a liver biopsy site in this monkey model. The findings obtained from the five monkey livers with similar anatomical features to human liver can be used as a reference for monitoring transplanted islets after clinical islet transplantation.
Highlights
The most obvious method to observe transplanted islets in the liver is direct biopsy, but the distribution and location of the best biopsy site in the recipient’s liver are poorly understood
Islet graft function was monitored based on the duration of normal glucose and serum C-peptide levels maintained without exogenous insulin (Supplemental Fig. S1)
To the best of our knowledge, no reports have been published on the distribution or characteristics of transplanted islets in the whole liver of cynomolgus monkeys
Summary
The most obvious method to observe transplanted islets in the liver is direct biopsy, but the distribution and location of the best biopsy site in the recipient’s liver are poorly understood. Islets transplanted into the whole liver of five diabetic cynomolgus monkeys that underwent insulin-independent survival for an extended period of time after allo-islet transplantation were analyzed for characteristics and distribution tendency. In islet transplantation studies, observing the transplanted islets in the recipient liver is very important because islets that have achieved insulin-independent normal glucose levels under various conditions during the early and extended periods after transplantation provide meaningful information that can aid progress in the islet transplantation field[12,13,14,15,16]. Noninvasive islet follow-up studies using magnetic resonance imaging (MRI) or computed tomography (CT) have been extensively performed and demonstrate the importance and risks of indirect liver biopsy[20,21,22,23,24,25,26,27,28]
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