Angiogenic effects of cell therapy within a biomaterial scaffold in a rat hind limb ischemia model.

Angiogenic effects of cell therapy within a biomaterial scaffold in a rat hind limb ischemia model.
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DOI:
10.1038/s41598-021-99579-0
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发表时间:
2021-10-15
期刊:
影响因子:
4.6
通讯作者:
Mortaz E
Mortaz E
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Amani S;Shahrooz R;Hobbenaghi R;Mohammadi R;Baradar Khoshfetrat A;Karimi A;Bakhtiari Z;Adcock IM;Mortaz E

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严重肢体缺血(CLI)是一种危及生命和肢体的疾病,影响全球1-10%的外周动脉疾病患者。细胞疗法,如骨髓来源的间充质干细胞(MSC)已被用于治疗CLI。然而,很少有关于骨髓间充质干细胞和肥大细胞(MC)在血管生成中的血管生成潜能的信息。本研究的目的是评估在组织工程水凝胶支架的背景下,MC和MSC在大鼠缺血性后肢损伤模型中诱导血管生成的能力。将30只大鼠随机分为6个对照组和实验组,如下所示:(a)对照健康组(B)右股动脉横断的缺血阳性对照组,(c)水凝胶支架缺血组,(d)水凝胶加MSC缺血组,(e)水凝胶加MC缺血组和(f)水凝胶加MSC和MC缺血组。将从骨髓基质分离的每种细胞类型的IO 6个注射到用于诱导后肢缺血的横切动脉中。另一条后肢作为非缺血对照。14天后,毛细血管密度,血管直径,组织形态计量学和免疫组织化学在横断位置和腓肠肌进行了评价。与对照组相比,接受MSC和MCs的动物中股动脉横断区域中的毛细血管密度和血管数量增加(P < 0.05)。一般来说,MC和MSC的作用是相似的,尽管MC/MSC联合治疗导致作用降低,而不是增强。腓肠肌组织形态计量学和免疫组化观察显示,各细胞组的毛细血管与肌纤维的比例均显著高于对照组(P < 0.05)。数据表明,水凝胶和细胞疗法的组合比单独的细胞疗法或水凝胶在缺血部位产生更大的血管生成潜力。
Critical limb ischemia (CLI) is a life- and limb-threatening condition affecting 1–10% of humans worldwide with peripheral arterial disease. Cellular therapies, such as bone marrow-derived mesenchymal stem cells (MSCs) have been used for the treatment of CLI. However, little information is available regarding the angiogenic potency of MSCs and mast cells (MC) in angiogenesis. The aim of this study was to evaluate the ability of MCs and MSCs to induce angiogenesis in a rat model of ischemic hind limb injury on a background of a tissue engineered hydrogel scaffold. Thirty rats were randomly divided into six control and experimental groups as follows: (a) Control healthy (b) Ischemic positive control with right femoral artery transection, (c) ischemia with hydrogel scaffold, (d) ischemia with hydrogel plus MSC, (e) ischemia with hydrogel plus MC and (f) ischemia with hydrogel plus MSC and MCs. 106 of each cell type, isolated from bone marrow stroma, was injected into the transected artery used to induce hind limb ischemia. The other hind limb served as a non-ischemic control. After 14 days, capillary density, vascular diameter, histomorphometry and immunohistochemistry at the transected location and in gastrocnemius muscles were evaluated. Capillary density and number of blood vessels in the region of the femoral artery transection in animals receiving MSCs and MCs was increased compared to control groups (P < 0.05). Generally the effect of MCs and MSCs was similar although the combined MC/MSC therapy resulted in a reduced, rather than enhanced, effect. In the gastrocnemius muscle, immunohistochemical and histomorphometric observation showed a great ratio of capillaries to muscle fibers in all the cell-receiving groups (P < 0.05). The data indicates that the combination of hydrogel and cell therapy generates a greater angiogenic potential at the ischemic site than cell therapy or hydrogels alone.
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