Promotion of Proangiogenic Secretome from Mesenchymal Stromal Cells via Hierarchically Structured Biodegradable Microcarriers.

Promotion of Proangiogenic Secretome from Mesenchymal Stromal Cells via Hierarchically Structured Biodegradable Microcarriers.
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DOI:
10.1002/adbi.202000062
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发表时间:
2020-07
影响因子:
4.1
通讯作者:
Day RM
Day RM
中科院分区:
生物学3区
文献类型:
--
作者:
Simitzi C;Hendow E;Li Z;Day RM

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脂肪源性间充质基质细胞(AdMSC)释放多种能够刺激血管生成的可溶性因子。现在寻求用于递送这些细胞以使其效力最大化的改进方法,理想地,它们将活细胞保留在靶组织中,同时促进血管生成因子的分泌。基质表面形貌是可用于操纵AdMSC行为的参数,但将该参数转化为与微创递送到组织中以原位递送血管生成分泌蛋白质组相容的材料存在挑战。目前的研究调查三个组成的层次结构,多孔可生物降解的微载体的AdMSC的文化和他们的表面形貌对血管生成分泌组的影响。所有三种组合物在无异种条件下作为细胞微载体表现良好。附着的AdMSC保留其随后的三系分化的能力。附着在微载体上的AdMSC分泌组由多种促血管生成因子组成,包括显着升高水平的血管内皮生长因子,其在体外刺激血管生成。本研究中研究的分层结构的多孔可生物降解微载体的独特性质提供了一种彻底变革的方法,用于实现AdMSC的体内靶向递送,并增强其促血管生成活性的效力,以诱导缺血组织中的新血管形成。本研究探讨了高度纹理微球设计用于植入式细胞微载体,显示出刺激分泌的促血管生成因子从附着的间充质基质细胞。这些研究结果表明,该技术可以通过靶向原位递送促进新血管生长的因子,为治疗心血管疾病提供一种可行且具有变革性的新方法。
Adipose‐derived mesenchymal stromal cells (AdMSC) release numerous soluble factors capable of stimulating angiogenesis. Improved methods for delivering these cells to maximize their potency are now sought that ideally they retain viable cells in the target tissue while promoting the secretion of angiogenic factors. Substrate surface topography is a parameter that can be used to manipulate the behavior of AdMSC but challenges exist with translating this parameter into materials compatible with minimally invasive delivery into tissues for in situ delivery of the angiogenic secretome. The current study investigates three compositions of hierarchically structured, porous biodegradable microcarriers for the culture of AdMSC and the influence of their surface topographies on the angiogenic secretome. All three compositions perform well as cell microcarriers in xeno‐free conditions. The attached AdMSC retain their capacity for subsequent trilineage differentiation. The secretome of AdMSC attached to the microcarriers consists of multiple proangiogenic factors, including significantly elevated levels of vascular endothelial growth factor, which stimulates angiogenesis in vitro. The unique properties of hierarchically structured, porous biodegradable microcarriers investigated in this study offer a radically transformative approach for achieving targeted in vivo delivery of AdMSC and enhancing the potency of their proangiogenic activity to induce neovascularization in ischemic tissue. This study investigates highly textured microspheres designed for use as implantable cell microcarriers that are shown to stimulate the secretion of proangiogenic factors from attached mesenchymal stromal cells. These findings suggest that the technology can provide a feasible and transformative new approach for treating cardiovascular disease through the targeted in situ delivery of factors that will promote new blood vessel growth.
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