Ma Yanling, Xu Yongsheng, Xiao Zhifeng, Yang Wei, Zhang Chun, Song E, Du Yiqin, Li Lingsong
Peking University Stem Cell Research Center and Cell Biology Department, The 3rd Hospital, Peking University Health Science Center, 38 Xueyuan Rd., Haidian, Beijing, China 100083.
Stem Cells. 2006 Feb;24(2):315-21. doi: 10.1634/stemcells.2005-0046. Epub 2005 Aug 18.
To examine whether transplantation of human mesenchymal stem cells (MSCs) could reconstruct the corneal damage and also whether grafted MSCs could differentiate into corneal epithelial cells, we isolated MSCs from healthy donors. After growth and expansion on amniotic membrane, cells were transplanted into rat corneas 7 days after chemical burns. Reconstruction of the damaged cornea and the rat vision were measured once a week by slit lamp and by an optokinetic head-tracking instrument, respectively. Corneas were then cut out, fixed, and imbedded for immunofluorescent study of the expression of keratin 3 and keratin-pan as epithelial cell markers. Expression of CD45, interleukin 2, and metalloproteinase-2 was also investigated for inflammation and inflammation-related angiogenesis. The data showed that transplantation of MSCs, like limbal epithelial stem cells, successfully reconstructed damaged rat corneal surface. Interestingly, the therapeutic effect of the transplantation may be associated with the inhibition of inflammation and angiogenesis after transplantation of MSCs rather than the epithelial differentiation from MSCs. This study provides the first line of evidence that MSCs can be used for reconstruction of damaged corneas, presenting a new source for autotransplantation in the treatment of corneal disorders.
为了研究人骨髓间充质干细胞(MSCs)移植是否能够修复角膜损伤,以及移植的MSCs是否能够分化为角膜上皮细胞,我们从健康供体中分离出了MSCs。在羊膜上生长和扩增后,于化学烧伤7天后将细胞移植到大鼠角膜中。分别每周一次通过裂隙灯和视动性头部跟踪仪测量受损角膜的修复情况和大鼠的视力。然后取出角膜,固定并包埋,用于免疫荧光研究角蛋白3和泛角蛋白作为上皮细胞标志物的表达。还研究了CD45、白细胞介素2和金属蛋白酶-2的表达,以了解炎症和炎症相关的血管生成情况。数据显示,与角膜缘上皮干细胞一样,MSCs移植成功修复了受损的大鼠角膜表面。有趣的是,移植的治疗效果可能与MSCs移植后炎症和血管生成的抑制有关,而不是与MSCs向上皮细胞的分化有关。本研究提供了首个证据表明MSCs可用于修复受损角膜,为角膜疾病的自体移植提供了一种新的来源。