Graduate Institute of Clinical Medicine, Taipei Medical University, and Center for Stem Cell Research, Wan Fang Hospital, Taipei, Taiwan.
Tissue Eng Part A. 2011 Jan;17(1-2):255-66. doi: 10.1089/ten.TEA.2010.0106. Epub 2010 Nov 29.
Loss of corneal epithelial cells results in visual problems. Stem cells isolated from the limbal area of the ocular surface are able to replenish lost corneal epithelial cells. However, destruction of the healthy limbus tissue is inevitable. Theoretically, orbital fat should be an excellent source to isolate stem cells for regenerating ocular tissues as the orbital connective tissues share the same embryonic origin with the ocular proper in early organogenesis. The aim of this study is to isolate stem cells from the human orbital fat and to explore their differentiation potentials into epithelial cells. It was found that spindle-shaped, fibroblast-like cells with extensive proliferation potentials could be isolated from orbital fat tissues. These orbital fat-derived stem cells (OFSCs) possessed multi-lineage differentiation potential to become osteoblasts, chondrocytes, and adipocytes. Upon mix-culture with corneal epithelial cells, OFSCs changed their morphology to round, polygonal epithelial-like cells. Loss of CD105 expression and increased expression of epithelial cell markers, including epithelial-specific antigen and zonal occludin-1, were found upon mix-culture with corneal epithelial cells. Moreover, corneal epithelial differentiation was evidenced by expression of cytokeratin -19 and cytokeratin -3 after mix-culture with corneal epithelial cells, whereas human adipose-derived stem cells from subcutaneous fat were unable to differentiate into corneal epithelial cells under the same induction condition. We further found that direct contact with corneal epithelial cells was essential for OFSCs to commit to corneal epithelial cells. Taken together, orbital fat tissues are a novel source for multi-potent stem cells that possess the potential to differentiate into corneal epithelial lineage. OFSCs are therefore a potential candidate for cell therapy and tissue engineering of corneal epithelium.
角膜上皮细胞的丧失会导致视力问题。从眼表面的角膜缘区分离出来的干细胞能够补充丢失的角膜上皮细胞。然而，健康的角膜缘组织的破坏是不可避免的。从理论上讲，眶脂肪应该是分离用于再生眼组织的干细胞的绝佳来源，因为眶结缔组织在早期器官发生中与眼本身具有相同的胚胎起源。本研究的目的是从人眶脂肪中分离干细胞，并探索其分化为上皮细胞的潜力。结果发现，可以从眶脂肪组织中分离出具有广泛增殖潜力的纺锤形、成纤维细胞样细胞。这些眶脂肪来源的干细胞（OFSCs）具有多能分化潜力，可分化为成骨细胞、软骨细胞和脂肪细胞。在与角膜上皮细胞共培养时，OFSCs 会改变其形态为圆形、多角形的上皮样细胞。与角膜上皮细胞共培养时，发现 CD105 表达丢失，上皮细胞标志物的表达增加，包括上皮特异性抗原和区域闭合蛋白-1。与角膜上皮细胞共培养后，还发现表达细胞角蛋白-19 和细胞角蛋白-3，表明发生了角膜上皮分化，而来自皮下脂肪的人脂肪来源干细胞在相同诱导条件下不能分化为角膜上皮细胞。我们进一步发现，与角膜上皮细胞的直接接触对于 OFSCs 向角膜上皮细胞分化是必需的。总之，眶脂肪组织是一种具有分化为角膜上皮谱系潜能的多潜能干细胞的新来源。因此，OFSCs 是角膜上皮细胞治疗和组织工程的潜在候选者。
