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Intraperitoneal injection of cell-engineered pancreas in rats with experimental type i diabetes (preliminary results)

https://doi.org/10.15825/1995-1191-2023-2-107-117

Abstract

Creation of a bioartificial pancreas, including a cell-engineered construct (CEC) formed from pancreatic islets (islets of Langerhans) and a biocompatible matrix mimicking the native microenvironment of pancreatic tissue, is one of the approaches to the treatment of type 1 diabetes mellitus (T1D).

Objective: to conduct preliminary in vivo studies of the functional efficacy of intraperitoneal injection of a cell-engineered pancreatic endocrine construct and a suspension of rat pancreatic islets in an experimental T1D model.

Materials and methods. Tissue-specific scaffold was obtained by decellularization of human pancreatic fragments. The viability and functional activity of rat islets isolated with collagenase were determined. Experimental T1D was modeled by intraperitoneal injection of low-dose streptozotocin and incomplete Freund’s adjuvant into rats. The rats were intraperitoneally injected twice with pancreatic CEC (n = 2) or islet suspension (n = 1). Glucose levels in the blood and urine of the rats were assessed. Histological examination of organs (pancreas and kidneys) of the experimental animals was carried out.

Results. After the first injection, blood glucose levels gradually decreased in all animals by more than 47% of the initial values; by follow-up day 24, the glucose level rose to the initial hyperglycemic values. After repeated administration, a 63.4% decrease in glycemic level was observed in the rats with pancreatic CEC and a 47.5% decrease in the one with islet suspension. At week 5 of the experiment, blood glucose levels gradually increased in all animals. At the same time, the glycemic index of the rat with injected pancreatic CEC was 62% lower than the glycemic index of the rat with injected islets.

Conclusion. Allogeneic pancreatic islets in pancreatic CEC increase the duration of stable glycemic level in T1D rats.

About the Authors

A. S. Ponomareva
Shumakov National Medical Research Center of Transplantology and Artificial Organs
Russian Federation

Anna Ponomareva

1, Shchukinskaya str., Moscow, 123182, Phone: (499) 196-26-61; (926) 585-23-73



N. V. Baranova
Shumakov National Medical Research Center of Transplantology and Artificial Organs
Russian Federation

Moscow



A. O. Nikolskaya
Shumakov National Medical Research Center of Transplantology and Artificial Organs
Russian Federation

Moscow



L. A. Kirsanova
Shumakov National Medical Research Center of Transplantology and Artificial Organs
Russian Federation

Moscow



N. A. Onishchenko
Shumakov National Medical Research Center of Transplantology and Artificial Organs
Russian Federation

Moscow



Z. Z. Gonikova
Shumakov National Medical Research Center of Transplantology and Artificial Organs
Russian Federation

Moscow



G. N. Bubentsova
Shumakov National Medical Research Center of Transplantology and Artificial Organs
Russian Federation

Moscow



Е. A. Volkova
Shumakov National Medical Research Center of Transplantology and Artificial Organs
Russian Federation

Moscow



Yu. B. Basok
Shumakov National Medical Research Center of Transplantology and Artificial Organs
Russian Federation

Moscow



V. I. Sevastianov
Shumakov National Medical Research Center of Transplantology and Artificial Organs
Russian Federation

Moscow



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Ponomareva A.S., Baranova N.V., Nikolskaya A.O., Kirsanova L.A., Onishchenko N.A., Gonikova Z.Z., Bubentsova G.N., Volkova Е.A., Basok Yu.B., Sevastianov V.I. Intraperitoneal injection of cell-engineered pancreas in rats with experimental type i diabetes (preliminary results). Russian Journal of Transplantology and Artificial Organs. 2023;25(2):107-117. https://doi.org/10.15825/1995-1191-2023-2-107-117

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ISSN 1995-1191 (Print)