Controlled epi-cortical delivery of epidermal growth factor for the stimulation of endogenous neural stem cell proliferation in stroke-injured brain
Controlled epi-cortical delivery of epidermal growth factor for the stimulation of endogenous neural stem cell proliferation in stroke-injured brain
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DOI：
10.1016/j.biomaterials.2011.04.032
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发表时间：
2011-08-01
期刊：
影响因子：
14
通讯作者：
Shoichet, Molly S.
中科院分区：
文献类型：
--
作者：
Cooke, Michael J.;Wang, Yuanfei;Shoichet, Molly S.
用生物分子治疗中枢神经系统（CNS）病症的挑战之一是实现局部递送，同时使侵入性最小化。对于中风的治疗，通过生长因子刺激内源性神经干/祖细胞（NSPCs）是一种有前途的组织再生策略。表皮生长因子（EGF）在直接递送至脑室时增强室管膜下区（SVZ）中内源性NSPCs的增殖;然而，这种策略是高度侵入性的。我们设计了一种基于生物材料的策略，将分子直接输送到大脑，而不会损伤组织。EGF或聚（乙二醇）-修饰的EGF（PEG-EGF）分散在透明质酸和甲基纤维素（HAMC）水凝胶，并放置epi-cortically对未受伤和中风受伤的小鼠大脑。PEG修饰降低了蛋白酶对EGF降解的速率，导致蛋白质积累在更大的组织深度比以前所示的显着增加。因此，EGF和PEG-EGF在未受伤和中风受伤的大脑中增加NSPC增殖;在中风受伤的大脑中，PEG-EGF显着增加NSPC刺激。我们的外皮层递送系统是一种用于局部递送到大脑的微创方法，为局部递送到大脑提供了新的范例。(C)2011爱思唯尔有限公司保留所有权利。
One of the challenges in treating central nervous system (CNS) disorders with biomolecules is achieving local delivery while minimizing invasiveness. For the treatment of stroke, stimulation of endogenous neural stem/progenitor cells (NSPCs) by growth factors is a promising strategy for tissue regeneration. Epidermal growth factor (EGF) enhances proliferation of endogenous NSPCs in the subventricular zone (SVZ) when delivered directly to the ventricles of the brain; however, this strategy is highly invasive. We designed a biomaterials-based strategy to deliver molecules directly to the brain without tissue damage. EGF or poly(ethylene glycol)-modified EGF (PEG-EGF) was dispersed in a hyaluronan and methylcellulose (HAMC) hydrogel and placed epi-cortically on both uninjured and stroke-injured mouse brains. PEG-modification decreased the rate of EGF degradation by proteases, leading to a significant increase in protein accumulation at greater tissue depths than previously shown. Consequently, EGF and PEG-EGF increased NSPC proliferation in uninjured and stroke-injured brains; and in stroke-injured brains, PEG-EGF significantly increased NSPC stimulation. Our epi-cortical delivery system is a minimally-invasive method for local delivery to the brain, providing a new paradigm for local delivery to the brain. (C) 2011 Elsevier Ltd. All rights reserved.