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

A. S. Ponomareva, N. Baranova, A. Nikolskaya, L. A. Kirsanova, N. Onishchenko, Z. Z. Gonikova, G. N. Bubentsova, Е. A. Volkova, Y. Basok, V. Sevastianov
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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.
实验性i型糖尿病大鼠腹腔注射细胞工程胰腺(初步结果)
生物人工胰腺的创建,包括由胰岛(朗格汉斯胰岛)和模拟胰腺组织原生微环境的生物相容性基质形成的细胞工程构建体(CEC),是治疗1型糖尿病(T1D)的方法之一。目的:在实验性T1D模型中,对腹腔注射细胞工程胰腺内分泌构建物和胰岛悬浮液对大鼠胰岛功能的影响进行初步体内研究。材料和方法。将人胰腺碎片脱细胞获得组织特异性支架。用胶原酶分离大鼠胰岛,测定其细胞活力和功能活性。采用腹腔注射低剂量链脲佐菌素和不完全弗氏佐剂的方法造模大鼠实验性T1D。大鼠腹腔注射胰腺CEC (n = 2)或胰岛悬浮液(n = 1)两次,评估大鼠血液和尿液中的葡萄糖水平。对实验动物各脏器(胰腺、肾脏)进行组织学检查。第一次注射后,所有动物的血糖水平逐渐下降,下降幅度超过初始值的47%;随访第24天,血糖水平上升至初始高血糖值。反复给药后,胰腺CEC大鼠血糖水平下降63.4%,胰岛悬浮大鼠血糖水平下降47.5%。实验第5周,所有动物的血糖水平逐渐升高。同时,注射胰腺CEC大鼠的血糖指数比注射胰岛大鼠的血糖指数低62%。胰腺CEC中的异体胰岛增加了T1D大鼠血糖水平稳定的持续时间。
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