Adipose-derived stromal vascular fraction cells isolated from old animals exhibit reduced capacity to support the formation of microvascular networks.

Adipose-derived stromal vascular fraction cells isolated from old animals exhibit reduced capacity to support the formation of microvascular networks.
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DOI:
10.1016/j.exger.2015.01.044
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发表时间:
2015-03
影响因子:
3.9
通讯作者:
LeBlanc, Amanda J.
LeBlanc, Amanda J.
中科院分区:
医学2区
文献类型:
--
作者:
Aird, Allison L.;Nevitt, Christopher D.;Christian, Katelyn;Williams, Stuart K.;Hoying, James B.;LeBlanc, Amanda J.

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脂肪来源的再生和干细胞,统称为基质血管成分(SVF),支持在植入部位形成新血管网络。评估了年龄增长对SVF细胞群对刺激的新血管形成的有效性的影响。从年轻(ySVF,4个月)或老年(oSVF,24个月)Fisher-344大鼠的脂肪中酶促分离SVF,与I型胶原结合并聚合。将包封的SVF皮下植入年轻的Rag 1小鼠中两周或四周。年龄依赖性SVF的血管生成功能也使用标准测定法在体外进行了广泛评价。体外研究表明ySVF和oSVF之间的血管生成功能(活力、增殖、迁移和管形成)无差异。在植入后两周,在植入的构建体中细胞凋亡百分比没有年龄相关的差异。到植入后4周,与ySVF相比,oSVF植入物显示总血管数/mm 2减少36%,灌注血管数/mm 2减少43%,并显示出更高的细胞凋亡百分比(n≥12)。与用对照抗体处理的oSVF植入物相比,阻断血栓反应蛋白-1(Thbs-1)(一种在oSVF中高度表达但在ySVF中不表达的蛋白质)在两周后增加了oSVF构建体中灌注血管体积和血管直径的百分比。供体年龄的增加降低了脂肪来源的SVF获得成熟微循环的潜力,但不妨碍初始血管生成。然而,Thbs-1的调节可以改善这种结果。这些数据表明,在oSVF中可能发生更大的修剪、功能失调的结构适应和/或伴随血流启动的不良成熟。
Adipose-derived regenerative and stem cells, defined collectively as the stromal vascular fraction (SVF), support the formation of neovascular networks at the site of implantation. The effect of advancing age on SVF cell population effectiveness toward stimulated neovascularization was evaluated. SVF was enzymatically isolated from adipose of young (ySVF, 4 mo) or old (oSVF, 24 mo) Fisher-344 rats, combined with type I collagen and polymerized. Encapsulated SVF was implanted subcutaneously into young Rag1 mice for two or four weeks. Angiogenic function of age-dependent SVF was also extensively evaluated in vitro using standard assays. In vitro studies indicated no difference in angiogenic function between ySVF and oSVF (viability, proliferation, migration, and tube-formation). At two weeks post-implantation, there was no age-related difference in percent apoptosis in explanted constructs. By four weeks post-implantation, oSVF implants displayed 36% less total vessels/mm2, 43% less perfused vessels/mm2, and exhibited greater percent apoptosis compared to ySVF (n≥12). Blocking Thrombospondin-1 (Thbs-1), a protein found to be highly expressed in oSVF but not ySVF, increased the percent of perfused vascular volume and vessel diameters in oSVF constructs after two weeks compared to oSVF implants treated with control antibody. Advancing donor age reduces the potential of adipose-derived SVF to derive a mature microcirculation, but does not hinder initial angiogenesis. However, modulation of Thbs-1 may improve this outcome. This data suggests that greater pruning, dysfunctional structural adaptation and/or poor maturation with initiation of blood flow may occur in oSVF.
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