The effect of controlled growth factor delivery on embryonic stem cell differentiation inside fibrin scaffolds
The effect of controlled growth factor delivery on embryonic stem cell differentiation inside fibrin scaffolds
复制标题
DOI：
10.1016/j.scr.2008.05.006
复制
发表时间：
2008-09-01
影响因子：
1.2
通讯作者：
Sakiyama-Elbert, Shelly E.
中科院分区：
文献类型：
--
作者：
Willerth, Stephanie M.;Rader, Allison;Sakiyama-Elbert, Shelly E.
该项目的目标是开发3-D生物材料支架，该支架提供线索以指导胚胎干（ES）细胞衍生的神经祖细胞分化，接种在支架内，成为成熟的神经表型，特别是神经元和少突胶质细胞。进行释放研究以确定通过结合到纤维蛋白支架中的基于亲和力的递送系统保留神经营养因子-3（NT-3）、音刺猬蛋白和血小板衍生生长因子（PDGF）的适当条件。使用4-/4+视黄酸处理方案，从小鼠ES细胞形成含有神经祖细胞的胚状体，然后将其接种在含有药物递送系统的纤维蛋白支架内。该递送系统用于将各种生长因子剂量和组合递送至接种在支架内的细胞。NT-3和PDGF的受控递送同时增加神经祖细胞、神经元和少突胶质细胞的分数，而与接种在培养基中不存在生长因子的未修饰纤维蛋白支架内的对照培养物相比，获得的星形胶质细胞的分数降低。这些结果表明，这种策略可以用于产生用于脊髓损伤的潜在治疗的工程组织，并可以扩展到其他组织的分化研究。(c)2008 Elsevier B. V.保留所有权利。
The goal of this project was to develop 3-D biomaterial scaffolds that present cues to direct the differentiation of embryonic stem (ES) cell-derived neural progenitor cells, seeded inside the scaffolds, into mature neural phenotypes, specifically neurons and oligodendrocytes. Release studies were performed to determine the appropriate conditions for retention of neurotrophin-3 (NT-3), sonic hedgehog, and platelet-derived growth factor (PDGF) by an affinity-based delivery system incorporated into fibrin scaffolds. Embryoid bodies containing neural progenitors were formed from mouse ES cells, using a 4-/4+ retinoic acid treatment protocol, and then seeded inside fibrin scaffolds containing the drug delivery system. This delivery system was used to deliver various growth factor doses and combinations to the cells seeded inside the scaffolds. Controlled delivery of NT-3 and PDGF simultaneously increased the fraction of neural progenitors, neurons, and oligodendrocytes while decreasing the fraction of astrocytes obtained compared to control cultures seeded inside unmodified fibrin scaffolds with no growth factors present in the medium. These results demonstrate that such a strategy can be used to generate an engineered tissue for the potential treatment of spinal cord injury and could be extended to the study of differentiation in other tissues. (c) 2008 Elsevier B.V. All rights reserved.