Nammian Pegah, Asadi-Yousefabad Seyedeh-Leili, Daneshi Sajad, Sheikhha Mohammad Hasan, Tabei Seyed Mohammad Bagher, Razban Vahid
Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Molecular Medicine, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Stem Cell Res Ther. 2021 Jan 13;12(1):58. doi: 10.1186/s13287-020-02110-x.
Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the in vitro and in vivo effects of allogeneic bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue mesenchymal stem cells (AT-MSCs) on CLI treatment.
For the first step, BM-MSCs and AT-MSCs were isolated and characterized for the characteristic MSC phenotypes. Then, femoral artery ligation and total excision of the femoral artery were performed on C57BL/6 mice to create a CLI model. The cells were evaluated for their in vitro and in vivo biological characteristics for CLI cell therapy. In order to determine these characteristics, the following tests were performed: morphology, flow cytometry, differentiation to osteocyte and adipocyte, wound healing assay, and behavioral tests including Tarlov, Ischemia, Modified ischemia, Function and the grade of limb necrosis scores, donor cell survival assay, and histological analysis.
Our cellular and functional tests indicated that during 28 days after cell transplantation, BM-MSCs had a great effect on endothelial cell migration, muscle restructure, functional improvements, and neovascularization in ischemic tissues compared with AT-MSCs and control groups.
Allogeneic BM-MSC transplantation resulted in a more effective recovery from critical limb ischemia compared to AT-MSCs transplantation. In fact, BM-MSC transplantation could be considered as a promising therapy for diseases with insufficient angiogenesis including hindlimb ischemia.
严重肢体缺血（CLI）是外周动脉疾病（PAD）的最严重形式，其特征为缺血性静息痛和不愈合溃疡。目前，CLI的标准治疗方法是手术重建和血管内治疗，对于没有治疗选择的患者则进行肢体截肢。间充质干细胞（MSCs）疗法诱导的新生血管形成是改善CLI的一种有前景的方法。由于其血管生成和免疫调节潜力，MSCs是治疗CLI的理想候选者。本研究的目的是确定并比较同种异体骨髓间充质干细胞（BM-MSCs）和脂肪组织间充质干细胞（AT-MSCs）对CLI治疗的体外和体内效果。
第一步，分离BM-MSCs和AT-MSCs并对其进行特征性MSC表型鉴定。然后，对C57BL/6小鼠进行股动脉结扎和股动脉完全切除以建立CLI模型。评估这些细胞用于CLI细胞治疗的体外和体内生物学特性。为了确定这些特性，进行了以下测试：形态学、流式细胞术、向骨细胞和脂肪细胞的分化、伤口愈合试验以及行为测试，包括塔尔洛夫评分、缺血评分、改良缺血评分、功能评分和肢体坏死分级评分、供体细胞存活试验以及组织学分析。
我们的细胞和功能测试表明，在细胞移植后的28天内，与AT-MSCs和对照组相比，BM-MSCs对缺血组织中的内皮细胞迁移、肌肉重构以及功能改善和新生血管形成具有显著作用。
与AT-MSCs移植相比，同种异体BM-MSC移植能使严重肢体缺血得到更有效的恢复。事实上，BM-MSC移植可被视为一种有前景的治疗方法，用于治疗包括后肢缺血在内的血管生成不足的疾病。
Zotero 插件
