vtioВестник трансплантологии и искусственных органовRussian Journal of Transplantology and Artificial Organs1995-1191Academician V.I.Shumakov National Medical Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation10.15825/1995-1191-2023-2-107-117vtio-1625Research ArticleРегенеративная медицина и клеточные технологииRegenerative Medicine and Cell TechnologiesВнутрибрюшинное введение клеточно-инженерной конструкции поджелудочной железы крысам с экспериментальным сахарным диабетом (предварительные результаты)Intraperitoneal injection of cell-engineered pancreas in rats with experimental type i diabetes (preliminary results)ПономареваА. С.PonomarevaA. S.

Пономарева Анна Сергеевна

123182, Москва, ул. Щукинская, д. 1. Тел.: (499) 196-26-61; (926) 585-23-73

Anna Ponomareva

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

a.s.ponomareva@gmail.comБарановаН. В.BaranovaN. V.

Наталья Владимировна Баранова

Москва

Moscow

barnats@yandex.ruНикольскаяА. О.NikolskayaA. O.

Алла Олеговна Никольская

Москва

Moscow

allanik64@yandex.ruКирсановаЛ. А.KirsanovaL. A.

Людмила Анфилофьевна Кирсанова

Москва

Moscow

lyudochkakirsanova@mail.ruОнищенкоН. А.OnishchenkoN. A.

Нина Андреевна Онищенко

Москва

Moscow

allanik64@yandex.ruГониковаЗ. З.GonikovaZ. Z.

Залина Залимгиреевна Гоникова

Москва

Moscow

allanik64@yandex.ruБубенцоваГ. Н.BubentsovaG. N.

Галина Николаевна Бубенцова

Москва

Moscow

barnats@yandex.ruВолковаЕ. А.VolkovaЕ. A.

Москва

Moscow

БасокЮ. Б.BasokYu. B.

Юлия Борисовна Басок

Москва

Moscow

bjb2005@mail.ruСевастьяновВ. И.SevastianovV. I.

Виктор Иванович Севастьянов

Москва

Moscow

viksev@yandex.ruФГБУ «Национальный медицинский исследовательский центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава РоссииРоссияShumakov National Medical Research Center of Transplantology and Artificial OrgansRussian Federation202315072023252107117Copyright © Пономарева А.С., Баранова Н.В., Никольская А.О., Кирсанова Л.А., Онищенко Н.А., Гоникова З.З., Бубенцова Г.Н., Волкова Е.А., Басок Ю.Б., Севастьянов В.И., 20232023Пономарева А.С., Баранова Н.В., Никольская А.О., Кирсанова Л.А., Онищенко Н.А., Гоникова З.З., Бубенцова Г.Н., Волкова Е.А., Басок Ю.Б., Севастьянов В.И.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 Y.B., Sevastianov V.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.transpl.ru/vtio/article/view/1625

Создание биоискусственной поджелудочной железы (ПЖ), в том числе клеточно-инженерной конструкции (КИК), сформированной на основе островков Лангерганса и биосовместимого матрикса, имитирующего нативное микроокружение панкреатической ткани, является одним из подходов к лечению сахарного диабета I типа (СД I).

Целью работы было проведение предварительных исследований in vivo функциональной эффективности внутрибрюшинного введения клеточно-инженерной конструкции эндокринного отдела поджелудочной железы и суспензии панкреатических островков крысы в экспериментальной модели СД I.

Материалы и методы

Материалы и методы. Тканеспецифический матрикс получали в результате децеллюляризации фрагментов ПЖ человека. Определяли жизнеспособность и функциональную активность островков крысы, выделенных с помощью коллагеназы. Экспериментальный СД I моделировали путем внутрибрюшинного введения малых доз стрептозотоцина и неполного адъюванта Фрейнда крысам. Крысам дважды вводили внутрибрюшинно КИК ПЖ (n = 2) или суспензию островков (n = 1). Оценивали уровень глюкозы в крови и моче крыс, а также проводили гистологическое исследование органов (поджелудочная железа и почки) экспериментальных животных.

Результаты

Результаты. После первого введения отмечали постепенное снижение уровня глюкозы в крови всех животных более чем на 47% от исходных значений, у которых к 24 суткам наблюдения происходил подъем уровня глюкозы до исходных гипергликемических показателей. После повторного введения наблюдали снижение уровня гликемии у животных с КИК ПЖ на 63,4% и на 47,5% – у крысы с суспензией островков. Через 5 недель эксперимента происходило постепенное повышение уровня глюкозы в крови у всех животных. При этом гликемический показатель крысы с введенной КИК ПЖ был на 62% ниже показателя гликемии у крысы с введенными островками.

Заключение

Заключение. В предварительных экспериментах показано, что аллогенные панкреатические островки в составе КИК ПЖ увеличивают длительность стабильного уровня гликемии у крыс с СД I.

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

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

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

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

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

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The authors declare that there are no conflicts of interest present.