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首页> 外文期刊>Cell transplantation >Improved cell survival and paracrine capacity of human embryonic stem cell-derived mesenchymal stem cells promote therapeutic potential for pulmonary arterial hypertension
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Improved cell survival and paracrine capacity of human embryonic stem cell-derived mesenchymal stem cells promote therapeutic potential for pulmonary arterial hypertension

机译：人类胚胎干细胞来源的间充质干细胞的细胞存活率和旁分泌能力的提高促进了肺动脉高压的治疗潜力

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Although transplantation of adult bone marrow mesenchymal stem cells (BM-MSCs) holds promise in the treatment for pulmonary arterial hypertension (PAH), the poor survival and differentiation potential of adult BM-MSCs have limited their therapeutic efficiency. Here, we compared the therapeutic efficacy of human embryonic stem cell-derived MSCs (hESC-MSCs) with adult BM-MSCs for the treatment of PAH in an animal model. One week following monocrotaline (MCT)-induced PAH, mice were randomly assigned to receive phosphate-buffered saline (MCT group); 3.0×106 human BM-derived MSCs (BM-MSCs group) or 3.0 ×106 hESC-derived MSCs (hESC-MSCs group) via tail vein injection. At 3 weeks posttransplantation, the right ventricular systolic pressure (RVSP), degree of RV hypertrophy, and medial wall thickening of pulmonary arteries were lower=, and pulmonary capillary density was higher in the hESC-MSC group as compared with BM-MSC and MCT groups (all p 0.05). At 1 week posttransplantation, the number of engrafted MSCs in the lungs was found significantly higher in the hESC-MSC group than in the BM-MSC group (all p 0.01). At 3 weeks posttransplantation, implanted BM-MSCs were undetectable whereas hESC-MSCs were not only engrafted in injured pulmonary arteries but had also undergone endothelial differentiation. In addition, protein profiling of hESC-MSC- and BM-MSC-conditioned medium revealed a differential paracrine capacity. Classification of these factors into bioprocesses revealed that secreted factors from hESC-MSCs were preferentially involved in early embryonic development and tissue differentiation, especially blood vessel morphogenesis. We concluded that improved cell survival and paracrine capacity of hESC-MSCs provide better therapeutic efficacy than BM-MSCs in the treatment for PAH.
机译：尽管成人骨髓间充质干细胞（BM-MSC）的移植有望在肺动脉高压（PAH）的治疗中发挥作用，但成人BM-MSC的存活率和分化潜能较差，限制了它们的治疗效率。在这里，我们比较了人类胚胎干细胞来源的MSC（hESC-MSC）和成年BM-MSC在动物模型中治疗PAH的疗效。在单肾上腺素（MCT）诱导的PAH后1周，将小鼠随机分配接受磷酸盐缓冲盐水（MCT组）;通过尾静脉注射获得3.0×106个人BM源MSC（BM-MSCs组）或3.0×106 hESC源MSC（hESC-MSCs组）。移植后3周，与BM-MSC和MCT相比，hESC-MSC组的右心室收缩压（RVSP），RV肥大程度和肺动脉内壁增厚较低，并且肺毛细血管密度较高。组（所有p <0.05）。移植后1周，hESC-MSC组的肺移植MSC数量明显高于BM-MSC组（所有p <0.01）。移植后3周，无法检测到植入的BM-MSC，而hESC-MSC不仅植入了受损的肺动脉，而且还经历了内皮分化。另外，hESC-MSC和BM-MSC条件培养基的蛋白质谱分析显示了不同的旁分泌能力。将这些因子分类为生物过程表明，hESC-MSC的分泌因子优先参与早期胚胎发育和组织分化，特别是血管形态发生。我们得出的结论是，hESC-MSC的改善的细胞存活率和旁分泌能力在治疗PAH方面比BM-MSC更好。

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