Peptide Nanofibers Preconditioned with Stem Cell Secretome Are Renoprotective
Peptide Nanofibers Preconditioned with Stem Cell Secretome Are Renoprotective
复制标题
DOI：
10.1681/asn.2010040403
复制
发表时间：
2011-04-01
影响因子：
13.6
通讯作者：
Danesh, Farhad R.
中科院分区：
文献类型：
--
作者：
Wang, Yin;Bakota, Erica;Danesh, Farhad R.
干细胞可能有助于急性肾损伤后的肾恢复，这可能通过其分泌细胞因子、趋化因子和生长因子而发生。在这里，我们开发了一种无细胞的、基于纳米纤维的自组装肽制剂，以递送胚胎干细胞（ESCs）的分泌组。使用一个集成的在体外和体内的方法，我们发现，与ESCs预处理的纳米纤维可以逆转细胞通透性过高和细胞凋亡在体外，并防止脂多糖诱导的急性肾损伤在体内。预处理纳米纤维的肾脏保护作用与Rho激酶激活的衰减相关。我们还观察到，在预处理过程中卵泡抑素，脂联素和分泌性白细胞蛋白酶的组合存在是必不可少的纳米纤维的肾脏保护性能。总之，我们开发了一种设计者-肽载体，其可以作为干细胞有益作用的递送平台，而没有畸胎瘤形成或有限的细胞移植和活力的问题。
Stem cells may contribute to renal recovery following acute kidney injury, and this may occur through their secretion of cytokines, chemokines, and growth factors. Here, we developed an acellular, nanofiber-based preparation of self-assembled peptides to deliver the secretome of embryonic stem cells (ESCs). Using an integrated in vitro and in vivo approach, we found that nanofibers preconditioned with ESCs could reverse cell hyperpermeability and apoptosis in vitro and protect against lipopolysaccharide-induced acute kidney injury in vivo. The renoprotective effect of preconditioned nanofibers associated with an attenuation of Rho kinase activation. We also observed that the combined presence of follistatin, adiponectin, and secretory leukoprotease during preconditioning was essential to the renoprotective properties of the nanofibers. In summary, we developed a designer-peptide nanofiber that can serve as a delivery platform for the beneficial effects of stem cells without the problems of teratoma formation or limited cell engraftment and viability.