Department of Plastic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People's Republic of China.
Innovative Technology Research Institute of Plastic Surgery, Guangzhou, 510630, People's Republic of China.
Stem Cell Rev Rep. 2024 Jan;20(1):313-328. doi: 10.1007/s12015-023-10641-y. Epub 2023 Oct 24.
Although Mesenchymal Stem Cells (MSCs)-based therapy has been proposed as a promising strategy for the treatment of chronic lower-extremity ulcers, their optimal sources, amounts, and delivery methods are urgently needed to be determined. In this study, we compared the heterogeneity of the human MSCs derived from bone marrow (BMSCs), umbilical cord (UCMSCs), and adipose tissue (ADSCs) in accelerating wound healing and promoting angiogenesis and explored the underlying mechanism. Briefly, a diabetic rat model with a full-thickness cutaneous wound on the dorsal foot was developed. The wound was topically administered with three types of MSCs. Additionally, we carried out in vitro and in vivo analysis of the angiogenic properties of the MSCs. Moreover, the molecular mechanism of the heterogeneity of the MSCs derived from the three tissues was explored by transcriptome sequencing. When compared with the BMSCs- and UCMSCs-treated groups, the ADSCs-treated group exhibited markedly accelerated healing efficiency, characterized by increased wound closure rates, enhanced angiogenesis, and collagen deposition at the wound site. The three types of MSCs formed three-dimensional capillary-like structures and promoted angiogenesis in vitro and in vivo, with ADSCs exhibiting the highest capacity for tube formation and pro-angiogenesis. Furthermore, transcriptome sequencing revealed that ADSCs had higher expression levels of angiogenesis-associated genes. Our findings indicate that MSCs-based therapy accelerates the healing of ischemia- and diabetes-induced lower-extremity ulcers and that adipose tissue-derived MSCs might be ideal for therapeutic angiogenesis and treatment of chronic ischemic wounds.
虽然间充质干细胞（MSCs）为治疗慢性下肢溃疡提出了一种很有前途的策略，但仍迫切需要确定其最佳来源、数量和输送方法。在这项研究中，我们比较了来源于骨髓（BMSCs）、脐带（UCMSCs）和脂肪组织（ADSCs）的人 MSCs 在加速伤口愈合和促进血管生成方面的异质性，并探讨了其潜在机制。简而言之，建立了足部背部全层皮肤创面的糖尿病大鼠模型。用三种 MSCs 对创面进行局部给药。此外，我们还对 MSCs 的血管生成特性进行了体外和体内分析。此外，通过转录组测序探讨了三种组织来源的 MSCs 异质性的分子机制。与 BMSCs 和 UCMSCs 处理组相比，ADSCs 处理组表现出明显加快的愈合效率，其特征是创面闭合率增加、血管生成增强以及创面部位的胶原沉积。三种类型的 MSCs 形成三维毛细血管样结构，并在体外和体内促进血管生成，其中 ADSCs 具有最高的管形成和促血管生成能力。此外，转录组测序显示 ADSCs 具有更高的血管生成相关基因的表达水平。我们的研究结果表明，MSCs 治疗可加速缺血性和糖尿病性下肢溃疡的愈合，脂肪组织来源的 MSCs 可能是治疗性血管生成和治疗慢性缺血性创面的理想选择。
