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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2020; 26(22): 2948-2966
Published online Jun 14, 2020. doi: 10.3748/wjg.v26.i22.2948
Regenerative medicine of pancreatic islets
Irina V Arutyunyan, Timur Kh Fatkhudinov, Andrey V Makarov, Andrey V Elchaninov, Gennady T Sukhikh
Irina V Arutyunyan, Andrey V Makarov, Andrey V Elchaninov, Gennady T Sukhikh, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V. I. Kulakov of Ministry of Healthcare of Russian Federation, Moscow 117997, Russia
Timur Kh Fatkhudinov, Research Institute of Human Morphology, Moscow 117418, Russia
Timur Kh Fatkhudinov, Peoples Friendship University of Russia, Moscow 117198, Russia
Andrey V Makarov, Pirogov Russian National Research Medical University, Ministry of Healthcare of the Russian Federation, Moscow 117997, Russia
Author contributions: Arutyunyan IV, Fatkhudinov TK, Makarov AV, Elchaninov AV, Sukhikh GT performed the literature review and wrote and edited portions of the final manuscript; all authors approved the submitted version of the manuscript.
Supported by the President Grant for Government Support of Young Russian Scientists, No. 075-15-2019-1120.
Conflict-of-interest statement: The authors do not have any commercial or other association that might pose a conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Timur Kh Fatkhudinov, MD, PhD, Deputy Director for Scientific Development, Laboratory of Growth and Development, Scientific Research Institute of Human Morphology, 3 Tsurupa Street, Moscow 117418, Russia. tfat@yandex.ru
Received: December 30, 2019
Peer-review started: December 30, 2019
First decision: January 19, 2020
Revised: May 13, 2020
Accepted: May 26, 2020
Article in press: May 26, 2020
Published online: June 14, 2020
Abstract

The pancreas became one of the first objects of regenerative medicine, since other possibilities of dealing with the pancreatic endocrine insufficiency were clearly exhausted. The number of people living with diabetes mellitus is currently approaching half a billion, hence the crucial relevance of new methods to stimulate regeneration of the insulin-secreting β-cells of the islets of Langerhans. Natural restrictions on the islet regeneration are very tight; nevertheless, the islets are capable of physiological regeneration via β-cell self-replication, direct differentiation of multipotent progenitor cells and spontaneous α- to β- or δ- to β-cell conversion (trans-differentiation). The existing preclinical models of β-cell dysfunction or ablation (induced surgically, chemically or genetically) have significantly expanded our understanding of reparative regeneration of the islets and possible ways of its stimulation. The ultimate goal, sufficient level of functional activity of β-cells or their substitutes can be achieved by two prospective broad strategies: β-cell replacement and β-cell regeneration. The “regeneration” strategy aims to maintain a preserved population of β-cells through in situ exposure to biologically active substances that improve β-cell survival, replication and insulin secretion, or to evoke the intrinsic adaptive mechanisms triggering the spontaneous non-β- to β-cell conversion. The “replacement” strategy implies transplantation of β-cells (as non-disintegrated pancreatic material or isolated donor islets) or β-like cells obtained ex vivo from progenitors or mature somatic cells (for example, hepatocytes or α-cells) under the action of small-molecule inducers or by genetic modification. We believe that the huge volume of experimental and clinical studies will finally allow a safe and effective solution to a seemingly simple goal-restoration of the functionally active β-cells, the innermost hope of millions of people globally.

Keywords: Pancreas, Islets of langerhans, β-cells, Regeneration, Replacement, Transplantation, Reprogramming

Core tip: The review discusses the most promising strategies for regenerative medicine to stimulate the regeneration or replacement of the islet of the pancreas. The “regeneration” strategy aims to maintain a preserved population of β-cells through replication, or evoke the intrinsic adaptive mechanisms. The “replacement” strategy implies transplantation of β-cells or β-like cells obtained ex vivo from progenitors or mature somatic cells (hepatocytes or α-cells). We believe that the huge volume of experimental and clinical studies currently under way will finally allow a safe and effective solution to simple goal-restoration of the active β-cells.