自愈水凝胶
间充质干细胞
体内
药物输送
再生医学
聚乙二醇
肝再生
PEG比率
全身给药
细胞凋亡
药理学
再生(生物学)
细胞生物学
材料科学
生物医学工程
干细胞
化学
医学
纳米技术
生物
生物化学
高分子化学
经济
生物技术
财务
作者
Soura Mardpour,Mohammad Hossein Ghanian,Hamid Sadeghi Abandansari,Saeid Mardpour,Abdoreza Nazari,Faezeh Shekari,Hossein Baharvand
标识
DOI:10.1021/acsami.9b10126
摘要
Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have been widely reported as promising cell-free products that show therapeutic effects of the parental cells but not their limitations. Due to the intrinsic liver tropism of MSC-EVs, they have been widely used as therapeutics or drug carriers for treatment of liver diseases. However, rapid clearance from the target site may attenuate the efficiency of systemically administered MSC-EVs. Herein, sustained release into the peritoneum has been proposed as a new strategy to prolong the bioavailability of the MSC-EVs in the target liver. During intraperitoneal injection, clickable polyethylene glycol (PEG) macromeres were mixed with MSC-EVs to form EV-encapsulated PEG hydrogels via a fast, biocompatible click reaction. Upon biodegradation, the EV-laden hydrogels were swollen gradually to release EVs in a sustained manner over 1 month. In vivo tracking of the labeled EVs revealed that the accumulation of EVs in the liver was extended by hydrogel-mediated delivery for 1 month. Four weeks after injection in a rat model of chronic liver fibrosis, the physical and histopathological investigations of the harvested liver showed superior antifibrosis, anti-apoptosis, and regenerative effects of the EVs when delivered by the sustained systemic release (Gel-EV) to the conventional bolus injection (Free-EV). Specifically, the Gel-EV system improved the antifibrosis, anti-inflammation, anti-apoptosis, and regenerative effects of the EVs to nearly 40, 50, 40, and 50% compared to Free-EV, respectively, as was specified by quantification of the fibrotic area, α-SMA density, and caspase-3 density in the harvested tissues and ALT enzyme in serum. This study may potentiate the use of MSC-EVs as cell-free therapeutics for chronic liver failure. The sustained systemic delivery strategy may open a new paradigm to extend the effects of disease-targeting EVs over time.
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