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纳米纤维支架上同时给予黄连素和子宫内膜干细胞衍生的胰岛素前体细胞移植治疗小鼠糖尿病。

Simultaneous Administration of Berberine and Transplantation of Endometrial Stem Cell-Derived Insulin Precursor Cells on a Nanofibrous Scaffold to Treat Diabetes Mellitus in Mice.

机构信息

Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran.

Department of Basic Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.

出版信息

Mol Neurobiol. 2023 Dec;60(12):7032-7043. doi: 10.1007/s12035-023-03540-3. Epub 2023 Aug 1.

Abstract

Today, significant success has been achieved in treating diabetes with cell therapy derived from various sources of stem and progenitors. The replacement of beta cells is one of the new diabetes treatment methods. To this end, the production of pancreatic beta precursors in cell culture has created an important research field for diabetes treatment. Endometrial stem cells were isolated using an enzymatic method, and after their identity was confirmed using a flow cytometry and differentiation potential assay, the isolated cells were cultured on an electrospun PCL/CS scaffold. Endometrial cells were differentiated into insulin-producing cells (IPCs), and gene expression was analyzed using the qRT-PCR and immunofluorescence to confirm the creation of IPCs. Then, IPCs on the scaffold along with berberine were applied to 5 groups of diabetic mice, and after 6 weeks, insulin, blood glucose, and weight of the animals were measured. The findings revealed that pancreatic markers were significantly expressed in IPCs compared to control cells. In addition, when compared to the control group and scaffolds, the receiving group of IPCs on scaffolds had a significant improvement (p ≤ 0.0015), and this improvement increased with the addition of berberine (decrease in blood sugar (133 mg/dL), and an increase in weight (5/39 g) and insulin (2.29 MIU/L). Thus, tissue engineering is a promising new strategy for treating diabetes and can be used in the future for cell therapy and suitable drugs for diabetic patients.

摘要

目前,通过源自不同来源的干细胞和祖细胞的细胞疗法,在治疗糖尿病方面已取得显著成功。β细胞的替代是新的糖尿病治疗方法之一。为此,在细胞培养中产生胰腺β前体细胞为糖尿病治疗创造了一个重要的研究领域。采用酶法分离子宫内膜干细胞,经流式细胞术和分化潜能检测鉴定其身份后,将分离的细胞培养在静电纺丝的 PCL/CS 支架上。将子宫内膜细胞分化为胰岛素生成细胞(IPCs),并通过 qRT-PCR 和免疫荧光分析来检测基因表达,以确认 IPC 的产生。然后,将支架上的 IPC 与黄连素一起应用于 5 组糖尿病小鼠,6 周后测量胰岛素、血糖和动物体重。研究结果表明,与对照细胞相比,IPCs 中胰腺标志物的表达明显。此外,与对照组和支架相比,支架上 IPC 的接受组有显著改善(p≤0.0015),并且随着黄连素的加入,这种改善会增加(血糖降低(133mg/dL),体重增加(5/39g)和胰岛素增加(2.29MIU/L)。因此,组织工程是治疗糖尿病的一种很有前途的新策略,将来可用于糖尿病患者的细胞治疗和合适药物。

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