Differentiation of multipotent stem cells to insulin-producing cells for treatment of diabetes mellitus: bone marrow- and adipose tissue-derived cells comparison.

Zahra Eydian,Ali Naghi Kamali,Reza Entezari Heravi,Laleh Rafighdoost,Sanaz Riki,Maryam Khosravi,Alaleh Mohammad Ghasemi,Samira Ansari,Sima Momtaz

doi:10.1007/s11033-022-07194-7

Abstract

Mesenchymal stem cells (MSCs) from human adipose tissue and bone marrow have a great potential for use in cell therapy due to their ease of isolation, expansion, and differentiation. Our intention was to isolate and promote in vitro expansion and differentiation of MSCs from human adipose and bone marrow tissue into cells with a pancreatic endocrine phenotype and to compare the potency of these cells together. MSCs were pre-induced with nicotinamide, mercaptoethanol, B-27 and b-FGF in L-DMEM for 2days and re-induced again in supplemented H-DMEM for another 3days. Expression of five genes in differentiated beta cells was evaluated by Real-time PCR and western blotting and the potency of insulin release in response to glucose stimulation was evaluated by insulin and C-peptide ELISA kit. The differentiated cells were evaluated by immunocytochemistry staining for Insulin and PDX-1. Quantitative RT-PCR results showed up-regulation of four genes in differentiated beta-islet cells (Insulin, Ngn-3, Pax-4 and Pdx-1) compared with the control. Western blot analysis showed that MSCs cells mainly produced proinsulin and insulin after differentiation but nestin was more expressed in pre-differentiated stem cells. Glucose and insulin secretion assay showed that insulin levels and C-peptide secretion were significantly increased in response to 10mM glucose. Our study showed that both adipose and bone marrow stem cells could differentiate into functional beta-islet cells but it seems that adipose stem cells could be a better choice for treatment of diabetes mellitus according to their higher potency.

Highlights

Insulin dependent diabetes mellitus (IDDM) is one of the most common chronic childhood diseases that caused usually by destruction of insulin-secreting pancreatic β-islet cells due to self-immune attack of Tlymphocytes [1]
Western blot analysis showed that mesenchymal stem cells (MSCs) cells mainly produced proinsulin and insulin after differentiation but nestin was more expressed in pre-differentiated stem cells
Our study showed that both adipose and bone marrow stem cells could differentiate into functional beta-islet cells but it seems that adipose stem cells could be a better choice for treatment of diabetes mellitus according to their more safety and potency

Summary

Introduction

Insulin dependent diabetes mellitus (IDDM) is one of the most common chronic childhood diseases that caused usually by destruction of insulin-secreting pancreatic β-islet cells due to self-immune attack of Tlymphocytes [1]. The properties of ADSCs render them well suited for applications in regenerative medicine and can provide a viable alternative for BMSCs. In this study we aimed to compare the potency of human ADSCs and BMSCs to differentiate to functional beta-islet pancreatic cells for in vitro insulin production that it may offer a potentially effective therapeutic approach in cell therapy. Mesenchymal stem cells (MSCs) from human adipose tissue and bone marrow have a great potential for use in cell therapy due to their ease of isolation, expansion, and differentiation. Our intention was to isolate and promote in vitro expansion and differentiation of MSCs from human adipose and bone marrow tissue into cells with a pancreatic endocrine phenotype and to compare the potency of these cells together

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Conclusion