Fibrillin-2 and Tenascin-C bridge the age gap in lung epithelial regeneration.
Fibrillin-2 and Tenascin-C bridge the age gap in lung epithelial regeneration.
复制标题
DOI：
10.1016/j.biomaterials.2017.06.027
复制
发表时间：
2017-09
期刊：
影响因子：
14
通讯作者：
Ott HC
中科院分区：
文献类型：
--
作者：
Gilpin SE;Li Q;Evangelista-Leite D;Ren X;Reinhardt DP;Frey BL;Ott HC
基于天然基质支架的器官工程包括将再生细胞群与相应的生物基质组合以按需形成功能性移植物。肺脱细胞化后保留的细胞外基质（ECM）为再细胞化后的整个器官再生提供了必要的结构和生物物理学线索。出生后早期肺中的独特ECM组合物，在活跃的肺泡形成期间，可能具有有助于驱动细胞粘附、存活和增殖的不同信号。我们评估了从成人肺组织分离的基底上皮干细胞（BESC）在来自新生儿（年龄< 1周）或成人肺供体（每组n=3个供体）的无细胞ECM上培养时的行为。我们接下来对肺支架进行了深入的蛋白质组学分析，以量化新生儿ECM中显著富集的蛋白质，并鉴定了糖蛋白Fibrillin-2（FBN-2）和Tenascin-C（TN-C）作为观察到的效果的潜在介质。在补充有FBN-2和TN-C的IV型胶原包被的板上培养的BESC显示出显著增加的增殖和减少的细胞衰老。未观察到上皮向间充质转化的显著增加。FBN-2和TN-C处理也增加了体外迁移。在再上皮化之前用FBN-2和TN-C处理的脱细胞肺支架支持更大的上皮增殖和组织重塑。在离体肺培养3天和7天后，BESC分布、基质排列和整体组织形态在经处理的肺支架上得到改善。这些结果表明，支架再上皮化在新生儿肺ECM上增强，并且向天然支架补充FBN-2和TN-C可能是肺组织再生中有价值的工具。
Organ engineering based on native matrix scaffolds involves combining regenerative cell populations with corresponding biological matrices to form functional grafts on-demand. The extracellular matrix (ECM) that is retained following lung decellularization provides essential structure and biophysical cues for whole organ regeneration after recellularization. The unique ECM composition in the early post-natal lung, during active alveologenesis, may possess distinct signals that aid in driving cell adhesion, survival, and proliferation. We evaluated the behavior of basal epithelial stem cells (BESCs) isolated from adult human lung tissue, when cultured on acellular ECM derived from neonatal (aged < 1 week) or adult lung donors (n=3 donors per group). A significant difference in cell proliferation and survival was found. We next performed in-depth proteomic analysis of the lung scaffolds to quantify proteins significantly enriched in the neonatal ECM, and identified the glycoproteins Fibrillin-2 (FBN-2) and Tenascin-C (TN-C) as potential mediators of the observed effect. BESCs cultured on Collagen Type IV coated plates, supplemented with FBN-2 and TN-C demonstrated significantly increased proliferation and decreased cellular senescence. No significant increase in epithelial-to-mesenchymal transition was observed. In vitro migration was also increased by FBN-2 and TN-C treatment. Decellularized lung scaffolds treated with FBN-2 and TN-C prior to re-epithelialization supported greater epithelial proliferation and tissue remodeling. BESC distribution, matrix alignment, and overall tissue morphology was improved on treated lung scaffolds, after 3 and 7 days of ex vivo lung culture. These results demonstrate that scaffold re-epithelialization is enhanced on neonatal lung ECM, and that supplementation of FBN-2 and TN-C to the native scaffold may be a valuable tool in lung tissue regeneration.
登录
查看更多内容
影响因子：
3.7
作者：
Godin LM;Sandri BJ;Wagner DE;Meyer CM;Price AP;Akinnola I;Weiss DJ;Panoskaltsis-Mortari A
通讯作者：
Panoskaltsis-Mortari A
影响因子：
3.8
作者：
Balestrini, Jenna L.;Niklason, Laura E.
通讯作者：
Niklason, Laura E.
影响因子：
8.9
作者：
Gilpin, Sarah Elizabeth;Guyette, Jacques P.;Ott, Harald C.
通讯作者：
Ott, Harald C.
影响因子：
4.8
作者：
Bax, DV;Bernard, SE;Kielty, CM
通讯作者：
Kielty, CM
影响因子：
4.8
作者：
Lin, GQ;Tiedemann, K;Reinhardt, DP
通讯作者：
Reinhardt, DP