Evaluation of in vivo and ex vivo pre-treated bone marrow-derived mesenchymal stem cells with resveratrol in streptozotocin-induced type 1 diabetic rats

J Pharm Pharmacol. 2023 Sep 1;75(9):1186-1197. doi: 10.1093/jpp/rgad042.

Abstract

Objectives: To compare the therapeutic potential of rat bone marrow-derived mesenchymal stem cells (BM-MSCs) preconditioned ex-vivo with resveratrol (MCR) and BM-MSCs isolated from resveratrol-pre-treated rats (MTR) in type-1 diabetic rats.

Methods: Type-1 diabetes was induced by a single streptozotocin injection (50 mg/kg; ip) in 24 rats. Following the confirmation of T1DM, diabetic rats were randomly divided into four groups: diabetic control (DC), diabetic rats treated with insulin subcutaneous (7.5 IU/kg/day), diabetic rats treated with MCR cells (3 × 106cells/rat, intravenous) and diabetic rats treated with MTR cells (3 × 106cells/rat, intravenous). Rats were sacrificed 4 weeks following cellular transplantation.

Key findings: Untreated diabetic rats suffered from pancreatic cell damage, had high blood glucose levels, increased apoptotic, fibrosis, and oxidative stress markers and decreased survival and pancreatic regeneration parameters. Both MSCs preconditioned ex-vivo with RES and MSCs isolated from rats pre-treated with RES homed successfully in injured pancreas and showed therapeutic potential in the treatment of STZ-induced T1DM. MCR cells showed better efficiency than MTR cells.

Conclusions: The pre-conditioning of BM-MSCs with resveratrol may be a promising therapeutic possibility in T1DM. Resveratrol-preconditioned BM-MSCs encouraged effects almost comparable to that of exogenous insulin with the advantages of cured pancreas and restored islets not attained by insulin.

Keywords: apoptosis; islet damage; pancreatic regeneration; resveratrol; survival.

MeSH terms

  • Animals
  • Bone Marrow
  • Diabetes Mellitus, Experimental* / chemically induced
  • Diabetes Mellitus, Experimental* / therapy
  • Diabetes Mellitus, Type 1* / chemically induced
  • Diabetes Mellitus, Type 1* / drug therapy
  • Insulin / pharmacology
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells*
  • Rats
  • Resveratrol / pharmacology
  • Streptozocin / pharmacology

Substances

  • Resveratrol
  • Streptozocin
  • Insulin