The effect of diabetes mellitus on differentiation of mesenchymal stem cells into insulin-producing cells

Omar I Badr; Mohamed M Kamal; Shohda A El-Maraghy; Heba R Ghaiad

doi:10.1186/s40659-024-00502-4

The effect of diabetes mellitus on differentiation of mesenchymal stem cells into insulin-producing cells

Biol Res. 2024 May 2;57(1):20. doi: 10.1186/s40659-024-00502-4.

Authors

Omar I Badr¹, Mohamed M Kamal^{1

2

3}, Shohda A El-Maraghy⁴, Heba R Ghaiad⁵

Affiliations

¹ Pharmacology and Biochemistry Department, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt.
² Drug Research and Development Group, Health Research Center of Excellence, The British University in Egypt, Cairo, Egypt.
³ Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
⁴ Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
⁵ Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt. heba.mosalam@pharma.cu.edu.eg.

Abstract

Background: Diabetes mellitus (DM) is a global epidemic with increasing incidences. DM is a metabolic disease associated with chronic hyperglycemia. Aside from conventional treatments, there is no clinically approved cure for DM up till now. Differentiating mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) is a promising approach for curing DM. Our study was conducted to investigate the effect of DM on MSCs differentiation into IPCs in vivo and in vitro.

Methods: We isolated adipose-derived mesenchymal stem cells (Ad-MSCs) from the epididymal fat of normal and STZ-induced diabetic Sprague-Dawley male rats. Afterwards, the in vitro differentiation of normal-Ad-MSCs (N-Ad-MSCs) and diabetic-Ad-MSCs (DM-Ad-MSCs) into IPCs was compared morphologically then through determining the gene expression of β-cell markers including neurogenin-3 (Ngn-3), homeobox protein (Nkx6.1), musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), and insulin-1 (Ins-1) and eventually, through performing glucose-stimulated insulin secretion test (GSIS). Finally, the therapeutic potential of N-Ad-MSCs and DM-Ad-MSCs transplantation was compared in vivo in STZ-induced diabetic animals.

Results: Our results showed no significant difference in the characteristics of N-Ad-MSCs and DM-Ad-MSCs. However, we demonstrated a significant difference in their abilities to differentiate into IPCs in vitro morphologically in addition to β-cell markers expression, and functional assessment via GSIS test. Furthermore, the abilities of both Ad-MSCs to control hyperglycemia in diabetic rats in vivo was assessed through measuring fasting blood glucose (FBGs), body weight (BW), histopathological examination of both pancreas and liver and immunoexpression of insulin in pancreata of study groups.

Conclusion: Our findings reveal the effectiveness of N-Ad-MSCs in differentiating into IPCs in vitro and controlling the hyperglycemia of STZ-induced diabetic rats in vivo compared to DM-Ad-MSCs.

Keywords: Adipose tissue; Diabetes mellitus; Differentiation; Insulin-producing cells; Mesenchymal stem cells.

MeSH terms

Animals
Blood Glucose / analysis
Cell Differentiation* / physiology
Cells, Cultured
Diabetes Mellitus, Experimental* / therapy
Insulin* / metabolism
Insulin-Secreting Cells* / metabolism
Male
Mesenchymal Stem Cell Transplantation / methods
Mesenchymal Stem Cells*
Rats
Rats, Sprague-Dawley*
Streptozocin

Substances

Insulin
Streptozocin
Blood Glucose