Department of Physiology, Medical University of Bialystok, Bialystok, Poland.
Diabetes Obes Metab. 2024 Mar;26(3):793-808. doi: 10.1111/dom.15375. Epub 2023 Dec 11.
Diabetes mellitus is a highly prevalent disease characterized by hyperglycaemia that damages the vascular system, leading to micro- (retinopathy, neuropathy, nephropathy) and macrovascular diseases (cardiovascular disease). There are also secondary complications of diabetes (cardiomyopathy, erectile dysfunction or diabetic foot ulcers). Stem cell-based therapies have become a promising tool targeting diabetes symptoms and its chronic complications. Among all stem cells, adipose-derived mesenchymal stem cells (ADMSCs) are of great importance because of their abundance, non-invasive isolation and no ethical limitations. Characteristics that make ADMSCs good candidates for cell-based therapy are their wide immunomodulatory properties and paracrine activities through the secretion of an array of growth factors, chemokines, cytokines, angiogenic factors and anti-apoptotic molecules. Besides, after transplantation, ADMSCs show great ex vivo expansion capacity and differentiation to other cell types, including insulin-producing cells, cardiomyocytes, chondrocytes, hepatocyte-like cells, neurons, endothelial cells, photoreceptor-like cells, or astrocytes. Preclinical studies have shown that ADMSC-based therapy effectively improved visual acuity, ameliorated polyneuropathy and foot ulceration, arrested the development and progression of diabetic kidney disease, or alleviated the diabetes-induced cardiomyocyte hypertrophy. However, despite the positive results obtained in animal models, there are still several challenges that need to be overcome before the results of preclinical studies can be translated into clinical applications. To date, there are several clinical trials or ongoing trials using ADMSCs in the treatment of diabetic complications, most of them in the treatment of diabetic foot ulcers. This narrative review summarizes the most recent outcomes on the usage of ADMSCs in the treatment of long-term complications of diabetes in both animal models and clinical trials.
糖尿病是一种高发疾病,其特征是高血糖,会损害血管系统,导致微血管(视网膜病变、神经病变、肾病)和大血管疾病(心血管疾病)。糖尿病还存在继发并发症(心肌病、勃起功能障碍或糖尿病足溃疡)。基于干细胞的疗法已成为一种有前途的治疗糖尿病症状及其慢性并发症的手段。在所有干细胞中,脂肪来源的间充质干细胞(ADMSCs)因其丰富、非侵入性的分离方法和无伦理限制而显得尤为重要。ADMSCs 作为细胞疗法的良好候选物的特性在于其广泛的免疫调节特性和旁分泌活性,通过分泌一系列生长因子、趋化因子、细胞因子、血管生成因子和抗细胞凋亡分子。此外,ADMSCs 在移植后具有很大的体外扩增能力,并能分化为其他细胞类型,包括产生胰岛素的细胞、心肌细胞、软骨细胞、肝细胞样细胞、神经元、内皮细胞、光感受器样细胞或星形胶质细胞。临床前研究表明,ADMSC 为基础的治疗有效地改善了视力,改善了多发性神经病和足部溃疡,阻止了糖尿病肾病的发展和进展,或缓解了糖尿病引起的心肌细胞肥大。然而,尽管在动物模型中获得了积极的结果,但在将临床前研究的结果转化为临床应用之前,仍有几个挑战需要克服。迄今为止,有几项临床试验或正在进行的临床试验使用 ADMSCs 治疗糖尿病并发症,其中大多数是治疗糖尿病足溃疡。本综述总结了 ADMSCs 在动物模型和临床试验中治疗糖尿病长期并发症的最新结果。
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