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Fortifying the angiogenic efficacy of adipose derived stem cell spheroids using spheroid compaction

机译:使用球形压实强化脂肪衍生的干细胞球体的血管生成效果

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Transplantation of stem cell spheroids to ischemic tissues has been suggested as an effective method for treating ischemic disease, but its therapeutic efficacy varies according to the preparation methods for spheroids. We hypothesized that increasing cell compaction while preparing spheroids could improve the angiogenic efficacy of spheroids. Optimized human adipose derived stem cell (hADSC) spheroids were shown to upregulate cell adhesion molecule, and angiogenic paracrine factors expression with downregulated senescence and apoptotic markers expression. We noted that the low seeding density (1 x 10(4) cells (10KS)) had a far lower probability of forming spheroids than higher seeding densities (3 x 10(4) cells (30KS) and 1 x 10(5) cells (100KS)). The 30KS spheroids demonstrated higher cell density and expression levels of the angiogenic paracrine factor expression compared to those of 100 KS spheroids. 30KS spheroids with additional incubation (A30KS) showed significantly increased angiogenic paracrine factors and cell adhesion molecule expressions with decreased senescence expression compared to those in 30KS spheroids. Transplanting A30KS spheroids showed significantly enhanced therapeutic angiogenesis in mouse hindlimb ischemia model compared to conventional spheroid transplantation. This study successfully defined a set of novel criteria for spheroid culture, which may contribute to future stem cell therapies. (C) 2020 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.
机译:将干细胞球体移植到缺血组织已被认为是治疗缺血性疾病的有效方法,但其治疗效果因球体的制备方法而异。我们假设,在制备球体的同时增加细胞密度可以提高球体的血管生成效率。优化的人脂肪源性干细胞(hADSC)球体可上调细胞粘附分子和血管生成旁分泌因子的表达,并下调衰老和凋亡标记物的表达。我们注意到,低播种密度(1 x 10(4)个细胞(10KS))形成球状体的概率远低于高播种密度(3 x 10(4)个细胞(30KS)和1 x 10(5)个细胞(100KS))。与100KS球体相比,30KS球体显示出更高的细胞密度和血管生成旁分泌因子表达水平。与30KS球体相比,额外孵育的30KS球体(A30KS)显示血管生成旁分泌因子和细胞粘附分子表达显著增加,衰老表达降低。在小鼠后肢缺血模型中,与常规球体移植相比,移植30KS球体可显著增强治疗性血管生成。这项研究成功地定义了一套新的球体培养标准,这可能有助于未来的干细胞治疗。(C) 2020年,韩国工业和工程化学学会。由爱思唯尔B.V.出版。版权所有。

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