Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, 01069 Dresden, Germany.
Biomaterials. 2013 Sep;34(28):6670-82. doi: 10.1016/j.biomaterials.2013.05.031. Epub 2013 Jun 14.
The use of exogenous signals is gaining importance in renal regenerative therapies. We wanted to explore the role of extracellular matrix (ECM) constituents on renal structure formation during renal organogenesis. We used a recently established organ culture setup to expose embryonic kidney rudiments directly to a large set of surface-immobilized or dissolved ECM molecules and growth factors. Organ culture was also performed on immobilized adult kidney ECM extracts and on reactive polymer films without any biomolecular components. The applied conditions resulted in distinct differences of organ phenotypes, underlining the multifaceted role of exogenous signals during kidney development. Specific ECM components, including collagen I and laminin, supported nephronal and tubular structure formation of the developing organ. ECM biopolymers, e.g. hyaluronic acid, were found to determine the fate of developing explants in a concentration- and molecular weight-dependent manner. The organ culture system used was an effective and robust means to identify exogenous signals that direct kidney development. This system can provide valuable insight for future regenerative therapies of kidney diseases.
外源性信号在肾脏再生治疗中变得越来越重要。我们希望探索细胞外基质 (ECM) 成分在肾脏器官发生过程中对肾脏结构形成的作用。我们使用了最近建立的器官培养设置,将胚胎肾原基直接暴露于大量表面固定或溶解的 ECM 分子和生长因子中。器官培养也在固定的成人肾脏 ECM 提取物和没有任何生物分子成分的反应性聚合物薄膜上进行。应用的条件导致器官表型的明显差异,强调了外源性信号在肾脏发育过程中的多方面作用。特定的 ECM 成分,包括胶原蛋白 I 和层粘连蛋白,支持发育中器官的肾单位和管状结构的形成。ECM 生物聚合物,例如透明质酸,被发现以浓度和分子量依赖的方式决定发育外植体的命运。所使用的器官培养系统是一种有效且强大的方法,可以识别指导肾脏发育的外源性信号。该系统可为肾脏疾病的未来再生治疗提供有价值的见解。