Osteogenic differentiation of human mesenchymal stem cells through alginate-graft-poly(ethylene glycol) microsphere-mediated intracellular growth factor delivery.
Osteogenic differentiation of human mesenchymal stem cells through alginate-graft-poly(ethylene glycol) microsphere-mediated intracellular growth factor delivery.
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DOI：
10.1016/j.jconrel.2014.06.029
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发表时间：
2014-10-28
期刊：
影响因子：
--
通讯作者：
Oldinski RA
中科院分区：
文献类型：
--
作者：
Miao T;Rao KS;Spees JL;Oldinski RA
生长因子的细胞内传递增加了控制细胞行为和维持组织稳态的机会。最近，有报道称VEGFA通过胞内机制促进间充质干细胞（mesenchymal stem cells, MSCs）的成骨分化，提示了一种促进骨质疏松患者骨组织形成的新策略。本研究的目的是设计和制造配体偶联海藻酸-移植物-聚乙二醇微球，用于在原代人间充质干细胞中细胞内递送和释放VEGFA，以增强成骨分化，作为一种潜在的治疗方法。合成了三种类型的微球，并通过扫描电镜、体外药物释放动力学、MSC摄取和内化进行了表征：单独海藻酸盐（Alg）、海藻酸盐接枝聚乙二醇（Algg-PEG）和海藻酸盐接枝聚乙二醇- s - s -精氨酸-甘氨酸-天冬氨酸（Alg-g- rgd）。每种不同的微球配方在培养48小时内成功地将生物活性VEGFA转运到原代人间充质干细胞中，与空白微球（细胞内对照）或未封装VEGFA（细胞外对照）的对照处理相比，显著增强了成骨分化。细胞内或细胞外VEGFA的存在不影响成脂分化。这些结果表明海藻酸微球的内化和VEGFA的细胞内递送支持使用这种药物递送和细胞内机制来控制人间充质干细胞的命运和增强成骨分化的有效性。
The intracellular delivery of growth factors increases opportunities for controlling cell behavior and maintaining tissue homeostasis. Recently, VEGFA was reported to enhance osteogenic differentiation of mesenchymal stem cells (MSCs) through an intracrine mechanism, suggesting a new strategy to promote bone tissue formation in osteoporotic patients. The goal of this study was to design and fabricate ligand-conjugated alginate-graft-poly(ethylene glycol) microspheres for intracellular delivery and release of VEGFA in primary human MSCs to enhance osteogenic differentiation as a potential therapeutic. Three types of microspheres were synthesized and characterized by scanning electron microscopy, in vitro drug release kinetics, MSC uptake and internalization: alginate alone (Alg), alginate-graft-poly(ethylene glycol) (Algg-PEG) and alginategraft-poly(ethylene glycol)-S-S-arginine-glycine-aspartic acid (Alg-g-RGD). Each of the different microsphere formulations successfully transported bioactive VEGFA into primary human MSCs within 48 h of culture, and significantly enhanced osteogenic differentiation compared to control treatments with empty microspheres (intracellular control) or non-encapsulated VEGFA (extracellular control). Adipogenic differentiation was not affected by the presence of VEGFA intracellularly or extracellularly. These results demonstrating the internalization of alginate-based microspheres and intracellular delivery of VEGFA support the efficacy of using this drug delivery and intracrine mechanism to control the fate of human MSCs and enhance osteogenic differentiation.
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DOI：
10.1016/j.jconrel.2008.10.019
发表时间：
2009-02-20
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Jay SM;Saltzman WM
通讯作者：
Saltzman WM
DOI：
10.1016/j.ejpb.2008.09.021
发表时间：
2009-03
期刊：
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
影响因子：
--
作者：
Kim S;Kim JH;Jeon O;Kwon IC;Park K
通讯作者：
Park K
影响因子：
5.2
作者：
Iso, Yoshitaka;Rao, Krithika S.;Poole, Charla N.;Zaman, A. K. M. Tarikuz;Curril, Ingrid;Sobel, Burton E.;Kajstura, Jan;Anversa, Piero;Spees, Jeffrey L.
通讯作者：
Spees, Jeffrey L.
影响因子：
4.1
作者：
Liu, Jun;Zhou, Hongzhi;Trotman, Carroll Ann
通讯作者：
Trotman, Carroll Ann
影响因子：
14
作者：
Gåserod, O;Sannes, A;Skjåk-Bræk, G
通讯作者：
Skjåk-Bræk, G