Generic placeholder image

Current Drug Discovery Technologies

Editor-in-Chief

ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

Research Article

Therapeutic Potential of Metformin-preconditioned Mesenchymal Stem Cells for Pancreatic Regeneration

Author(s): Prajakta Kamble, Shivani Desai*, Ramesh Bhonde*, Avinash Sanap, Jagruti Shimpi, Rohit Kumbhar, Manesh Kokani and Avinash Kharat

Volume 20, Issue 3, 2023

Published on: 05 April, 2023

Article ID: e090323214492 Pages: 7

DOI: 10.2174/1570163820666230309094233

Price: $65

Abstract

Background: Diabetes occurs due to insulin deficiency or less insulin. To manage this condition, insulin administration as well as increased insulin sensitivity is required, but exogeneous insulin cannot replace the sensitive and gentle regulation of blood glucose levels same as β cells of healthy individuals. By considering the ability of regeneration and differentiation of stem cells, the current study planned to evaluate the effect of metformin preconditioned buccal fat pad (BFP) derived mesenchymal stem cells (MSCs) on streptozotocin (STZ) induced diabetes mellitus in Wistar rats.

Materials & Methods: The disease condition was established by using a diabetes-inducing agent STZ in Wistar rats. Then, the animals were grouped into disease control, blank, and test groups. Only the test group received the metformin-preconditioned cells. The total study period for this experiment was 33 days. During this period, the animals were monitored for blood glucose level, body weight, and food-water intake twice a week. At the end of 33 days, the biochemical estimations for serum insulin level and pancreatic insulin level were performed. Also, histopathology of the pancreas, liver and skeletal muscle was performed.

Results: The test groups showed a decline in the blood glucose level and an increase in the serum pancreatic insulin level as compared to the disease group. No significant change in food and water intake was observed within the three groups, while body weight was significantly reduced in the test group when compared with the blank group, but the life span was increased when compared with the disease group.

Conclusion: In the present study, we concluded that metformin preconditioned buccal fat pad-derived mesenchymal stem cells have the ability to regenerate damaged pancreatic β cells and have antidiabetic activity, and this therapy is a better choice for future research.

Graphical Abstract

[1]
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2014; 37 (Suppl. 1): S81-90.
[http://dx.doi.org/10.2337/dc14-S081] [PMID: 24357215]
[2]
Vija L, Farge D, Gautier JF, et al. Mesenchymal stem cells: Stem cell therapy perspectives for type 1 diabetes. Diabetes Metab 2009; 35(2): 85-93.
[http://dx.doi.org/10.1016/j.diabet.2008.10.003] [PMID: 19230736]
[3]
McCall AL. Insulin therapy and hypoglycemia. Endocrinol Metab Clin North Am 2012; 41(1): 57-87.
[http://dx.doi.org/10.1016/j.ecl.2012.03.001] [PMID: 22575407]
[4]
Lebovitz HE. Insulin: Potential negative consequences of early routine use in patients with type 2 diabetes. Diabetes Care 2011; 34 (Suppl. 2): S225-30.
[http://dx.doi.org/10.2337/dc11-s225] [PMID: 21525460]
[5]
Robertson P, Davis C, Larsen J, Stratta R, Sutherland DE. Pancreas transplantation in type 1 diabetes. Diabetes Care 2004; 27 (Suppl. 1): s105.
[http://dx.doi.org/10.2337/diacare.27.2007.S105] [PMID: 14693941]
[6]
Weems P, Cooper M. Pancreas transplantation in type II diabetes mellitus. World J Transplant 2014; 4(4): 216-21.
[http://dx.doi.org/10.5500/wjt.v4.i4.216] [PMID: 25540731]
[7]
Farge DO, Vija LA, Gautier JF, et al. Mesenchymal stem cells-stem cell therapy perspectives for type 1 diabetes. Proceedings of the Romanian Academy, Series B: Chemistry, Life Sciences and Geosciences. 10(1-2): 59-70.
[8]
Bottino R, Trucco M, Balamurugan AN, Starzl TE. Pancreas and islet cell transplantation. Best Pract Res Clin Gastroenterol 2002; 16(3): 457-74.
[http://dx.doi.org/10.1053/bega.2002.0318] [PMID: 12079269]
[9]
Abdi R, Fiorina P, Adra CN, Atkinson M, Sayegh MH. Immunomodulation by mesenchymal stem cells: A potential therapeutic strategy for type 1 diabetes. Diabetes 2008; 57(7): 1759-67.
[http://dx.doi.org/10.2337/db08-0180] [PMID: 18586907]
[10]
Nojehdehi S, Soudi S, Hesampour A, Rasouli S, Soleimani M, Hashemi SM. Immunomodulatory effects of mesenchymal stem cell–derived exosomes on experimental type‐1 autoimmune diabetes. J Cell Biochem 2018; 119(11): 9433-43.
[http://dx.doi.org/10.1002/jcb.27260] [PMID: 30074271]
[11]
Katuchova J, Harvanova D, Spakova T, et al. Mesenchymal stem cells in the treatment of type 1 diabetes mellitus. Endocr Pathol 2015; 26(2): 95-103.
[http://dx.doi.org/10.1007/s12022-015-9362-y] [PMID: 25762503]
[12]
Cao X, Han ZB, Zhao H, Liu Q. Transplantation of mesenchymal stem cells recruits trophic macrophages to induce pancreatic beta cell regeneration in diabetic mice. Int J Biochem Cell Biol 2014; 53: 372-9.
[http://dx.doi.org/10.1016/j.biocel.2014.06.003] [PMID: 24915493]
[13]
Khatri R, Mazurek S, Petry SF, Linn T. Mesenchymal stem cells promote pancreatic β-cell regeneration through downregulation of FoxO1 pathway. Stem Cell Res Ther 2020; 11(1): 497.
[http://dx.doi.org/10.1186/s13287-020-02007-9] [PMID: 33239104]
[14]
Milanesi A, Lee JW, Li Z, et al. β-Cell regeneration mediated by human bone marrow mesenchymal stem cells. PLoS One 2012; 7(8): e42177.
[http://dx.doi.org/10.1371/journal.pone.0042177] [PMID: 22879915]
[15]
Dave S. Mesenchymal stem cells derived in vitro transdifferentiated insulin-producing cells: A new approach to treat type 1 diabetes. Adv Biomed Res 2014; 3(1): 266.
[http://dx.doi.org/10.4103/2277-9175.148247] [PMID: 25625105]
[16]
Shree N, Bhonde RR. Conditioned media from adipose tissue derived mesenchymal stem cells reverse insulin resistance in cellular models. J Cell Biochem 2017; 118(8): 2037-43.
[http://dx.doi.org/10.1002/jcb.25777] [PMID: 27791278]
[17]
Sanap A, Chandravanshi B, Shah T, et al. Herbal pre-conditioning induces proliferation and delays senescence in wharton’s jelly mesenchymal stem cells. Biomed Pharmacother 2017; 93: 772-8.
[http://dx.doi.org/10.1016/j.biopha.2017.06.107] [PMID: 28724259]
[18]
Meng XM, Ma XX, Tian YL, et al. Metformin improves the glucose and lipid metabolism via influencing the level of serum total bile acids in rats with streptozotocin-induced type 2 diabetes mellitus. Eur Rev Med Pharmacol Sci 2017; 21(9): 2232-7.
[PMID: 28537659]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy