Surface Tethering of Inflammation-Modulatory Nanostimulators to Stem Cells for Ischemic Muscle Repair.
Surface Tethering of Inflammation-Modulatory Nanostimulators to Stem Cells for Ischemic Muscle Repair.
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DOI：
10.1021/acsnano.9b04926
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发表时间：
2020-05-26
期刊：
影响因子：
17.1
通讯作者：
Kong H
中科院分区：
文献类型：
--
作者：
Leong J;Hong YT;Wu YF;Ko E;Dvoretskiy S;Teo JY;Kim BS;Kim K;Jeon H;Boppart M;Yang YY;Kong H
在过去的十年中，干细胞移植是一种很有前途的治疗外周动脉疾病的方法。干细胞是组织再生的旁分泌因子的活生物反应器。预刺激脂肪源性干细胞（ADSCs）已被提出作为潜在的候选者，但在激活其分泌活性用于临床应用方面遇到了挑战。在此，我们提出将释放肿瘤坏死因子α (TNFα)的纳米颗粒（称为纳米刺激剂）系在ADSC表面，可以原位刺激细胞分泌活性。我们通过将十八烷基胺移植的透明质酸络合到TNFα的脂质体载体上来检验这一假设。透明质酸增加了脂质体的稳定性和与ADSC表面CD44的关联。与这些TNFα载体连接的ADSCs显示出促血管生成血管内皮生长因子和免疫调节前列腺素E2 （PGE2）的分泌上调，而抗血管生成色素上皮源性因子的分泌降低。因此，与未处理的ADSCs相比，与纳米刺激器连接的ADSCs促进了3D微血管芯片中的血管化，并增强了小鼠缺血后肢的灌注恢复、行走和肌肉质量。我们建议这种原位刺激干细胞的表面系缚策略将取代昂贵和繁琐的预处理过程，并加快干细胞在临床中的应用，以改善各种损伤和疾病的治疗。
Stem cell transplantation has been a promising treatment for peripheral arterial diseases in the past decade. Stem cells act as living bioreactors of paracrine factors that orchestrate tissue regeneration. Prestimulated adipose-derived stem cells (ADSCs) have been proposed as potential candidates but have been met with challenges in activating their secretory activities for clinical use. Here, we propose that tethering the ADSC surface with nanoparticles releasing tumor necrosis factor α (TNFα), named nanostimulator, would stimulate cellular secretory activity in situ. We examined this hypothesis by complexing octadecylamine-grafted hyaluronic acid onto a liposomal carrier of TNFα. Hyaluronic acid increased the liposomal stability and association to CD44 on ADSC surface. ADSCs tethered with these TNFα carriers exhibited up-regulated secretion of proangiogenic vascular endothelial growth factor and immunomodulatory prosteoglandin E2 (PGE2) while decreasing secretion of antiangiogenic pigment epithelium-derived factors. Accordingly, ADSCs tethered with nanostimulators promoted vascularization in a 3D microvascular chip and enhanced recovery of perfusion, walking, and muscle mass in a murine ischemic hindlimb compared to untreated ADSCs. We propose that this surface tethering strategy for in situ stimulation of stem cells would replace the costly and cumbersome preconditioning process and expedite clinical use of stem cells for improved treatments of various injuries and diseases.
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内吞作用未插入：多种进入细胞的方法。
影响因子：
44.1
作者：
Kumari S;Mg S;Mayor S
通讯作者：
Mayor S
影响因子：
5.2
作者：
Lee, Sang Yoon;Kim, Won;Chung, Sun G.
通讯作者：
Chung, Sun G.
影响因子：
4.1
作者：
Anderson, Erin M.;Kwee, Brian J.;Mooney, David J.
通讯作者：
Mooney, David J.
影响因子：
14
作者：
Cheng, Hao;Byrska-Bishop, Marta;Zhang, Cathy T.;Kastrup, Christian J.;Hwang, Nathaniel S.;Tai, Albert K.;Lee, Won Woo;Xu, Xiaoyang;Nahrendorf, Matthias;Langer, Robert;Anderson, Daniel G.
通讯作者：
Anderson, Daniel G.
影响因子：
4.6
作者：
Ankrum JA;Dastidar RG;Ong JF;Levy O;Karp JM
通讯作者：
Karp JM