Schlötzer-Schrehardt U, Freudenberg U, Kruse F E
Augenklinik, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schwabachanlage 6, 91054, Erlangen, Deutschland.
Leibniz Institute of Polymer Research Dresden (IPF), Max Bergmann Center of Biomaterials Dresden (MBC), Hohe Str. 6, 01069, Dresden, Deutschland.
Ophthalmologe. 2017 Apr;114(4):327-340. doi: 10.1007/s00347-017-0468-0.
Limbal stem cells reside in a highly specialized complex microenvironment that is known as the stem cell niche, an anatomically protected region at the bottom of the Palisades of Vogt, where the stem cells are located and where their quiescence, proliferation and differentiation are maintained in balance. Besides the epithelial stem and progenitor cell clusters, the limbal niche comprises several types of supporting niche cells and a specific extracellular matrix mediating biochemical and biophysical signals. Stem cell-based tissue engineering aims to mimic the native stem cell niche and to present appropriate microenvironmental cues in a controlled and reproducible fashion in order to maintain stem cell function within the graft. Current therapeutic approaches for ex vivo expansion of limbal stem cells only take advantage of surrogate niches. However, new insights into the molecular composition of the limbal niche and innovative biosynthetic scaffolds have stimulated novel strategies for niche-driven stem cell cultivation. Promising experimental approaches include collagen-based organotypic coculture systems of limbal epithelial stem cells with their niche cells and biomimetic hydrogel platforms prefunctionalized with appropriate biomolecular and biophysical signals. Future translation of these novel regenerative strategies into clinical application is expected to improve long-term outcomes of limbal stem cell transplantation for ocular surface reconstruction.
角膜缘干细胞存在于一个高度特化的复杂微环境中，即所谓的干细胞生态位，它是位于沃格特嵴底部的一个解剖学上受到保护的区域，干细胞就位于此处，其静止、增殖和分化在此处保持平衡。除了上皮干细胞和祖细胞簇外，角膜缘生态位还包括几种类型的支持性生态位细胞以及介导生化和生物物理信号的特定细胞外基质。基于干细胞的组织工程旨在模拟天然干细胞生态位，并以可控且可重复的方式呈现适当的微环境线索，以维持移植物内的干细胞功能。目前用于角膜缘干细胞体外扩增的治疗方法仅利用了替代生态位。然而，对角膜缘生态位分子组成的新见解和创新的生物合成支架激发了基于生态位驱动的干细胞培养的新策略。有前景的实验方法包括角膜缘上皮干细胞与其生态位细胞的基于胶原蛋白的器官型共培养系统，以及用适当的生物分子和生物物理信号预功能化的仿生水凝胶平台。预计这些新型再生策略在未来转化为临床应用将改善用于眼表重建的角膜缘干细胞移植的长期效果。
