Experimental implantation of tissue-engineering pancreatic construct

Aim: to study the effect of implantation of tissue-engineering pancreatic construct (TEPC) on the course of experimental diabetes mellitus.

Materials and methods. The TEPC samples received as a result of joint incubation in vitro floating islet-like cultures (FILC), obtained from the pancreas of newborn rabbits, and the biopolymer microheterogeneous collagen hydrogel (BMCH). Stable diabetes mellitus was caused in Wistar rats by the method of fractional streptozotocin administration.

Results. The formation of TEPC occurred at 7-10 days of incubation FILC with BMCH. At the same time, the presence of β-cells with insulin-producing activity was revealed in the TEPC. After intraperitoneal implantation of TEPC samples in rats with streptozotocin diabetes mellitus, there was a significant and persistent decrease in glycemia until the end of the 8-week period of the experiment. Morphological study of pancreas of recipient rats revealed signs of regeneration of own β-cells.

Conclusion. The data obtained suggest the combined antidiabetic effect of intraperitoneal injection of TEPC, due to both the direct functioning of the implant and its stimulating effect on the regeneration of β-cells in their own islets of rats with streptozotocin diabetes mellitus.

1. Maffi P, Secchi A. Clinical results of islet transplantation. Pharmacol Res. 2015; 98: 86-91. doi: 10.1016/j.phrs.2015.04.010 CrossRefPubMed.

2. Shapiro AMJ. State of the art of clinical islet transplantation and novel protocols of immunosuppression. Curr Diabetes Rep. 2011; 11: 345-354. doi: 10.1007/s11892-011-0217-8 CrossRef.

3. Amer LD, Mahoney MJ, Bryant SJ. Tissue Engineering Approaches to Cell-Based Type 1 Diabetes. Therapy Tissue Engineering Part B: Reviews. October 2014; 20 (5): 455-467. doi: 10.1089/ten.teb.2013.0462.

4. Skaletskiy NN, Kirsanova LA, Sevastyanov VI. Razrabotka i eksperimentalnoe issledo-vanie tkaneinzhenernykh konstruktsiy podzheludochnoy zhelezy iz kultur ostrovkovykh kletok i biodegradirue-mykh nositeley s tselyu stimulatsii regeneratsii p-kletok u bolnykh sakharnym diabetom. Transplantologia: itogi i perspektivy. Tom V. 2013 god. Pod red. S.V Gautier. M.-Tver’: Triada, 2014: 140-152.

5. Skaletskaya GN, Sevastya-nov VI. Eksperimentalnaya model tkaneinzhenernoy konstruktsii podzheludochnoy zhelezy. Transplanto-logia: itogi i perspektivy. Tom IX. 2017 god. Pod red. S.V. Gautier. M.-Tver’: Triada, 2018: 283-299.

6. Sevastya-nov VI, Perova NV. Inyektsionniy geterogenniy biopo-limerniy gidrogel dla zamestitelnoy regenerativnoy khi-rurgii i sposoby ego polucheniya. Patent RF 2433828 (2010).

7. Sevastyanov VI, Shagidulin MYu, Skaletskiy NN, Perova NV Dovzhik IA, Gautier SV Doklinicheskiye issledovaniya bezopasnosti i effektivnosti BMKP dla regeneratsii sustavnogo khrya-shcha, pecheni i podzheludochnoy zhelezy. Metodiches-kiye rekomendatsii po provedeniyu doklinicheskikh issledovaniy biomeditsinskykh kletochnykh produktov. Pod red. akad. V.A. Tkachuka M.: MGU, 2017: 187-255.

8. Cirulli V, Beattie GM, Klier G. Expression and function of alpha(v)beta(3) and alpha(v)beta(5) integrins in the developing pancreas: roles in the adhesion and migration of putative endocrine progenitor cells. J. Cell Biol. 2000; 150: 1445-1460.

9. Bogdanova NB, Abramov VYu, Skaletskiy NN, Petrova IA, Pushkova IA, Baranova NV, Bubentsova GN. Iss-ledovanie fiksatsii syvorotochnykh immunoglobulinov cheloveka na kultivirovannykh ostrovkovykh kletkakh podzheludochnoy zhelezy. IV Vserossiyskiy s’yezd trans-plantologov. M., 2008: 227-228.