Neo-vascularization of the stroke cavity by implantation of human neural stem cells on VEGF-releasing PLGA microparticles.

Neo-vascularization of the stroke cavity by implantation of human neural stem cells on VEGF-releasing PLGA microparticles.
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DOI:
10.1016/j.biomaterials.2012.06.085
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发表时间:
2012-10
期刊:
影响因子:
14
通讯作者:
Modo, Michel
Modo, Michel
中科院分区:
工程技术1区
文献类型:
--
作者:
Bible, Ellen;Qutachi, Omar;Chau, David Y. S.;Alexander, Morgan R.;Shakesheff, Kevin M.;Modo, Michel

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替代中风后失去的组织可能提供新的神经基质以促进恢复。然而,需要克服重大的神经生物学和生物技术挑战,使这种可能性成为现实。人类神经干细胞(hNSCs)可以分化成成熟的脑细胞,但需要一个结构支持,将它们保留在腔内,并提供从头组织的形成。然而,在我们之前的工作中,即使在一周后,这种原始组织也缺乏能够维持其长期生存能力的脉管系统。因此,需要组织工程策略来开发脉管系统。血管内皮生长因子(VEGF)是已知的血管和动脉生成过程中促进内皮细胞的增殖和迁移。VEGF本身并不影响hNSCs的生存力或分化,而在有或没有VEGF的情况下,在聚(D,L-乳酸-共-乙醇酸)(PLGA)微粒上生长的细胞使星形胶质细胞和神经元分化加倍。分泌的爆发和持续交付的VEGF从微粒在体内吸引内皮细胞从主机到这个灵长类动物组织,并在部分建立一个新的血管,而在其他部分内皮细胞只是散布与hNSC。还有证据表明存在血运过度,这表明需要进一步研究以建立足够的血运水平。因此,有可能在由中风引起的组织腔内形成的新生组织内形成推定的新血管系统。
Replacing the tissue lost after a stroke potentially provides a new neural substrate to promote recovery. However, significant neurobiological and biotechnological challenges need to be overcome to make this possibility into a reality. Human neural stem cells (hNSCs) can differentiate into mature brain cells, but require a structural support that retains them within the cavity and affords the formation of a de novo tissue. Nevertheless, in our previous work, even after a week, this primitive tissue is void of a vasculature that could sustain its long-term viability. Therefore, tissue engineering strategies are required to develop a vasculature. Vascular endothelial growth factor (VEGF) is known to promote the proliferation and migration of endothelial cells during angio- and arteriogenesis. VEGF by itself here did not affect viability or differentiation of hNSCs, whereas growing cells on poly(D,L-lactic acid-co-glycolic acid) (PLGA) microparticles, with or without VEGF, doubled astrocytic and neuronal differentiation. Secretion of a burst and a sustained delivery of VEGF from the microparticles in vivo attracted endothelial cells from the host into this primate tissue and in parts established a neovasculature, whereas in other parts endothelial cells were merely interspersed with hNSCs. There was also evidence of a hypervascularization indicating that further work will be required to establish an adequate level of vascularization. It is therefore possible to develop a putative neovasculature within de novo tissue that is forming inside a tissue cavity caused by a stroke.
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