Simultaneous Subtotal Pancreatectomy and Streptozotocin Injection for Diabetes Modeling in Cynomolgus Monkeys

Park, H.; Park, J.B.; Kim, J.H.; Lee, K.W.; Lee, H.S.; Kim, G.-S.; Shin, Du Yeon; Oh, Seung Hoon; Jin, Sang‐Man; Kim, S.J.

doi:10.1016/j.transproceed.2017.03.012

Cited by 8 publications

(10 citation statements)

References 21 publications

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“…In our three monkeys that used both ATG and rituximab, there were no differences in the factors related to the normalization of blood glucose level, especially the B cell in ltration affected by rituximab. This result is presumed to have been affected by our method of inducing diabetes, in which we removed the pancreas and spleen together, as previously described 18,33 .…”

Section: Discussionmentioning

confidence: 99%

Marginal Transplantation Dose Study for the Treatment of Insulin-independent Type 1 Diabetes After Allogeneic Islet Transplantation in Macaca Fascicularis Monkeys

Kim

Cho

Lee³

et al. 2021

Preprint

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Many groups are working to improve the results of clinical allogeneic islet transplantation in a primate model. However, few studies have focused on the optimal islet dose for achieving normal glycemia without exogenous insulin after transplantation in primate models or on the relationship between rejection and islet amyloid polypeptide (IAPP) expression. We evaluated the dose (group 1/10,000, group 2/20,000, and group 3/>25,000 islet equivalents (IEQ)/kg) needed to achieve normal glycemia without exogenous insulin after transplantation using eleven cynomolgus monkeys, and we analyzed the characteristics exhibited in the islets after transplantation. Group 1 (n2) failed to control blood glucose level, despite injection with the highest dose of exogenous insulin, and group 2 (n5) achieved unstable control, with a high insulin requirement. However, group 3 (n4) achieved normal glycemia without exogenous insulin and maintained it for more than 60 days. Immunohistochemistry results from staining islets found in liver biopsies indicated that as the number of transplanted islets decreased, the amount of IAPP accumulation within the islets increased, which accelerated immune cell infiltration. In conclusion, the marginal transplantation dose for achieving a normal glycemia without exogenous insulin in our cynomolgus monkey model was >25,000 IEQ/kg, and the accumulation of IAPP early after transplantation, which depends on the transplanted islet dose, can be considered one factor in rejection.

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Section: Discussionmentioning

confidence: 99%

Marginal Transplantation Dose Study for the Treatment of Insulin-independent Type 1 Diabetes After Allogeneic Islet Transplantation in Macaca Fascicularis Monkeys

Kim

Cho

Lee³

et al. 2021

Preprint

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“…An STP/LD-STZ model was previously reported in rhesus monkeys [2,18], and recently in cynomolgus monkeys as well [19]. However, a comparison of different dosages of STZ in cynomolgus monkeys with functional and morphological correlation was essential to minimize the utilized dosage.…”

Section: Discussionmentioning

confidence: 99%

A Simple and Effective Non-Human Primate Diabetic Model Combining Sub-Total Pancreatectomy and Low-Dose Streptozotocin Injection

Fathi¹,

Imura²,

Imura³

et al. 2019

obm transplant

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“…The average weight and age of the five male monkeys were 3.5 ± 0.1 kg and 57.6 ± 4.3 months, respectively. All procedures related to infection screening, housing, handling, care and treatment in this study were performed as previously described 53 . The study was approved by the Institutional Animal Care and Use Committee of Orient Bio Laboratories (ORIENT-IACUC-13001) and the experiments were performed in accordance with the relevant guidelines and regulations.…”

Section: Methodsmentioning

confidence: 99%

“…induction of diabetes mellitus in cynomolgus monkeys. All procedures for the induction, confirmation, and maintenance of type 1 diabetes in cynomolgus monkeys were performed as previously described 53 . Briefly, diabetes was induced by injecting 60 mg/kg streptozotocin (Sigma, St. Louis, MO, USA) after surgical removal of >70% of the recipient monkey's pancreas.…”

Section: Methodsmentioning

confidence: 99%

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Integrated whole liver histologic analysis of the allogeneic islet distribution and characteristics in a nonhuman primate model

Kim

Lee²,

Shin

et al. 2020

Sci Rep

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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.

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Simultaneous Subtotal Pancreatectomy and Streptozotocin Injection for Diabetes Modeling in Cynomolgus Monkeys

Cited by 8 publications

References 21 publications

Marginal Transplantation Dose Study for the Treatment of Insulin-independent Type 1 Diabetes After Allogeneic Islet Transplantation in Macaca Fascicularis Monkeys

Marginal Transplantation Dose Study for the Treatment of Insulin-independent Type 1 Diabetes After Allogeneic Islet Transplantation in Macaca Fascicularis Monkeys

A Simple and Effective Non-Human Primate Diabetic Model Combining Sub-Total Pancreatectomy and Low-Dose Streptozotocin Injection

Integrated whole liver histologic analysis of the allogeneic islet distribution and characteristics in a nonhuman primate model

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