Department of Vascular Surgery, Ganzhou People's Hospital, the Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, Jiangxi, China; Vascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
Department of Vascular Surgery, Ganzhou People's Hospital, the Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, Jiangxi, China.
Biochem Pharmacol. 2021 Aug;190:114530. doi: 10.1016/j.bcp.2021.114530. Epub 2021 Apr 21.
Peripheral arterial disease (PAD) is an increasingly common narrowing of the peripheral arteries that can lead to lower limb ischemia, muscle weakness and gangrene. Surgical vein or arterial grafts could improve PAD, but may not be suitable in elderly patients, prompting research into less invasive approaches. Mesenchymal stem cells (MSCs) have been proposed as potential therapy, but their effectiveness and underlying mechanisms in limb ischemia are unclear. We tested the hypothesis that treatment with naive MSCs (nMSCs) or MSCs expressing CD146 (MSCs) could improve vascularity and muscle function in rat model of hind-limb ischemia. Sixteen month old Sprague-Dawley rats were randomly assigned to 4 groups: sham-operated control, ischemia, ischemia + nMSCs and ischemia+MSCs. After 4 weeks of respective treatment, rat groups were assessed for ischemic clinical score, Tarlov score, muscle capillary density, TUNEL apoptosis assay, contractile force, and vascular endothelial growth factor (VEGF) mRNA expression. MSCs showed greater CD146 mRNA expression than nMSCs. Treatment with nMSCs or MSCs improved clinical and Tarlov scores, muscle capillary density, contractile force and VEGF mRNA expression in ischemic limbs as compared to non-treated ischemia group. The improvements in muscle vascularity and function were particularly greater in ischemia+MSCs than ischemia + nMSCs group. TUNEL positive apoptotic cells were least abundant in ischemia+MSCs compared with ischemia + nMSCs and non-treated ischemia groups. Thus, MSCs particularly those expressing CD146 improve vascularity, muscle function and VEGF expression and reduce apoptosis in rat ischemic limb, and could represent a promising approach to improve angiogenesis and muscle function in PAD.
外周动脉疾病（PAD）是外周动脉狭窄的一种常见疾病，可导致下肢缺血、肌肉无力和坏疽。外科静脉或动脉移植物可改善 PAD，但在老年患者中可能不适用，因此研究人员正在探索创伤更小的方法。间充质干细胞（MSCs）已被提议作为潜在的治疗方法，但它们在肢体缺血中的有效性和潜在机制尚不清楚。我们假设用未成熟的 MSCs（nMSCs）或表达 CD146 的 MSCs（MSCs）治疗可以改善大鼠后肢缺血模型的血管生成和肌肉功能。将 16 个月大的 Sprague-Dawley 大鼠随机分为 4 组：假手术对照组、缺血组、缺血+ nMSCs 组和缺血+MSCs 组。经过 4 周的治疗后，评估各组大鼠的缺血临床评分、Tarlov 评分、肌肉毛细血管密度、TUNEL 凋亡检测、收缩力和血管内皮生长因子（VEGF）mRNA 表达。MSCs 的 CD146 mRNA 表达高于 nMSCs。与未治疗的缺血组相比，nMSCs 或 MSCs 治疗可改善缺血肢体的临床和 Tarlov 评分、肌肉毛细血管密度、收缩力和 VEGF mRNA 表达。与缺血+ nMSCs 组相比，缺血+MSCs 组的肌肉血管生成和功能改善更为显著。与缺血+ nMSCs 组和未治疗的缺血组相比，缺血+MSCs 组的 TUNEL 阳性凋亡细胞最少。因此，MSCs，特别是表达 CD146 的 MSCs，可改善大鼠缺血肢体的血管生成、肌肉功能和 VEGF 表达，并减少细胞凋亡，可能是改善 PAD 血管生成和肌肉功能的有前途的方法。
