Mesenchymal stem cells can be recruited to wounded tissue via hepatocyte growth factor‐loaded biomaterials

Mesenchymal stem cells can be recruited to wounded tissue via hepatocyte growth factor‐loaded biomaterials
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间充质干细胞可以通过负载肝细胞生长因子的生物材料招募到受伤组织

DOI:
10.1002/term.2201
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发表时间:
2016
影响因子:
3.3
通讯作者:
Neuss S
Neuss S
中科院分区:
工程技术3区
文献类型:
--
作者:
van de Kamp J;Paefgen V;Wöltje M;Böbel M;Rheinnecker M;Jaekel J;Labude N;Rath B;Knüchel R;Jahnen-Dechent W;Neuss S

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间充质干细胞(MSC)是中胚层组织的前体细胞,并且由于其营养表型,已知它们在伤口愈合中发挥有益作用。此外,各种组织工程策略是基于MSC/生物材料构建体。由于间充质干细胞的分离和扩增是一个长期的过程,主要目标是开发一种内源性干细胞募集系统,以避免通常用于组织工程的体内步骤。因此,胶原蛋白和丝素蛋白负载有肝细胞生长因子(HGF),一种用于MSC的化学引诱物。胶原蛋白在聚合过程中与HGF混合,而丝素蛋白和HGF通过转基因蚕作为融合蛋白产生。为了证明活性HGF的释放,进行了酶联免疫吸附试验、体外迁移试验和动物研究,以证明MSC体内迁移,然后详细检查生物材料的免疫学效应。肝细胞生长因子在体外前8 h内从丝素蛋白和胶原蛋白中呈爆发式释放,并逐渐释放至168 h。体外实验表明,当MSCs暴露于HGF时,可以定向迁移。体内实验表明,载HGF的胶原蛋白和丝素蛋白作为皮下植入物是耐受的。此外,已证明内源性MSC是从局部环境中募集的。这些结果首次显示了内源性MSC在体外和体内向负载HGF的胶原蛋白(快速可降解)和丝素蛋白支架(长期可降解)的募集。这些知识可用于制造现成的、现成的结构,用于慢性伤口或烧伤患者。版权所有© 2016约翰威利父子有限公司.
Mesenchymal stem cells (MSC) are precursor cells of mesodermal tissue and, because of their trophic phenotype, they are known to play beneficial roles in wound healing. In addition, various tissue engineering strategies are based on MSC/biomaterial constructs. As the isolation and expansion of MSCs is a long‐term process, a major goal is to develop an endogenous stem cell recruitment system that circumvents allex vivosteps generally used for tissue engineering. Therefore collagen and silk fibroin were loaded with hepatocyte growth factor (HGF), a chemoattractant for MSCs. Collagen was mixed with HGF during polymerization, while silk fibroin and HGF were produced as fusion proteins by transgenic silkworms. To demonstrate release of active HGF, enzyme‐linked immunosorbent assay,in vitromigration assays and animal studies were performed to demonstrate MSC migrationin vivo, followed by detailed examinations of the immunological effects of the biomaterials. Hepatocyte growth factor was released burst‐like, both from silk fibroin and collagen during the first 8 h and gradually for up to 168 hin vitro. Directed migrationin vitrowas demonstrated when MSCs were exposed to HGF.In vivo, HGF‐loaded collagen and silk fibroin were tolerated as subcutaneous implants. In addition, it was proved that endogenous MSCs were recruited from the local environment. These results show for the first time recruitment of endogenous MSCs to HGF‐loaded collagen (fast degradable) and silk fibroin scaffolds (long‐term degradable)in vitroandin vivo. This knowledge could be applied to make off‐the‐shelf, readily available constructs for use in patients with chronic wound or burns. Copyright © 2016 John Wiley & Sons, Ltd.