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

IF 4.3 2区生物学 Q1 BIOLOGY

Biological Research Pub Date : 2024-05-02 DOI:10.1186/s40659-024-00502-4

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

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Abstract

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. 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. 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. 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.

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糖尿病对间充质干细胞分化为胰岛素分泌细胞的影响

糖尿病（DM）是一种全球性流行病，发病率不断上升。糖尿病是一种与慢性高血糖有关的代谢性疾病。除了传统治疗方法外，迄今为止还没有临床认可的治疗糖尿病的方法。将间充质干细胞（MSCs）分化为胰岛素分泌细胞（IPCs）是治疗DM的一种很有前景的方法。我们的研究旨在探讨DM对间充质干细胞在体内和体外分化为IPCs的影响。我们从正常大鼠和 STZ 诱导的糖尿病 Sprague-Dawley 雄性大鼠的附睾脂肪中分离出脂肪间充质干细胞（Ad-MSCs）。随后，比较了正常-Ad-间充质干细胞（N-Ad-MSCs）和糖尿病-Ad-间充质干细胞（DM-Ad-MSCs）在体外分化成 IPCs 的形态学结果，并通过测定神经原蛋白-3（Ngn-3）、同工酶蛋白（Nkx6.1）、肌肉神经纤维肉瘤癌基因同源物 A（MafA）和胰岛素-1（Ins-1）等β细胞标志物的基因表达，最后通过葡萄糖刺激胰岛素分泌试验（GSIS）进行检测。最后，在 STZ 诱导的糖尿病动物体内比较了 N-Ad-MSCs 和 DM-Ad-MSCs 移植的治疗潜力。结果显示，N-Ad-间充质干细胞和DM-Ad-间充质干细胞的特性没有明显差异。然而，我们发现它们在体外分化成 IPC 的能力除了在形态学上有显著差异外，在 β 细胞标志物表达和通过 GSIS 测试进行功能评估方面也有显著差异。此外，我们还通过测量研究组大鼠的空腹血糖（FBGs）、体重（BW）、胰腺和肝脏的组织病理学检查以及胰岛素在胰腺中的免疫表达，评估了两种 Ad-MSCs 在体内控制糖尿病大鼠高血糖的能力。我们的研究结果表明，与 DM-Ad-MSCs 相比，N-Ad-MSCs 能有效地在体外分化成 IPC，并控制 STZ 诱导的糖尿病大鼠体内的高血糖。

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来源期刊

Biological Research 生物-生物学

CiteScore

10.10

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Biological Research is an open access, peer-reviewed journal that encompasses diverse fields of experimental biology, such as biochemistry, bioinformatics, biotechnology, cell biology, cancer, chemical biology, developmental biology, evolutionary biology, genetics, genomics, immunology, marine biology, microbiology, molecular biology, neuroscience, plant biology, physiology, stem cell research, structural biology and systems biology.