Cell therapy of congenital corneal diseases with umbilical mesenchymal stem cells: lumican null mice.
Cell therapy of congenital corneal diseases with umbilical mesenchymal stem cells: lumican null mice.
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DOI：
10.1371/journal.pone.0010707
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发表时间：
2010-05-19
期刊：
影响因子：
3.7
通讯作者：
Kao WW
中科院分区：
文献类型：
--
作者：
Liu H;Zhang J;Liu CY;Wang IJ;Sieber M;Chang J;Jester JV;Kao WW
角膜移植是治疗角膜失明的最有效方法，但在发展中国家，医疗条件不佳、缺乏合格的医务人员和捐献的角膜往往阻碍了角膜移植的开展。本研究旨在开发针对基因突变的先天性角膜疾病的替代治疗方案。从新生脐带分离的人骨髓间充质干细胞移植治疗LUMICAN缺陷型小鼠薄而混浊的角膜。脐带间充质干细胞移植显著改善了LUMICAN空白小鼠的角膜透明度，增加了基质厚度，但人脐血间充质干细胞未能做到这一点。进一步的研究表明，间充质干细胞移植后，LUMICA缺陷型小鼠角膜基质中的胶原层发生了重组。移植的脐间充质干细胞在小鼠角膜基质中存活了3个月以上，几乎没有移植排斥反应。此外，这些细胞呈角质细胞表型，如树突状细胞形态、静止期、表达角质细胞特有的角蛋白硫化角质形成蛋白和LUMICAN，以及CD34。此外，脐带间充质干细胞移植改善了宿主角膜细胞的功能，这一点在Lumcan基因缺失的小鼠中得到了证实，角蛋白和乙醛脱氢酶3A1类的表达增强。脐间充质干细胞移植是治疗先天性角膜疾病合并角膜基质细胞功能障碍的一种很有前途的治疗方法。与捐献的角膜不同，脐带间充质干细胞很容易分离、扩增、储存，并可以在患者急需时从液氮中快速恢复。
Keratoplasty is the most effective treatment for corneal blindness, but suboptimal medical conditions and lack of qualified medical personnel and donated cornea often prevent the performance of corneal transplantation in developing countries. Our study aims to develop alternative treatment regimens for congenital corneal diseases of genetic mutation. Human mesenchymal stem cells isolated from neonatal umbilical cords were transplanted to treat thin and cloudy corneas of lumican null mice. Transplantation of umbilical mesenchymal stem cells significantly improved corneal transparency and increased stromal thickness of lumican null mice, but human umbilical hematopoietic stem cells failed to do the same. Further studies revealed that collagen lamellae were re-organized in corneal stroma of lumican null mice after mesenchymal stem cell transplantation. Transplanted umbilical mesenchymal stem cells survived in the mouse corneal stroma for more than 3 months with little or no graft rejection. In addition, these cells assumed a keratocyte phenotype, e.g., dendritic morphology, quiescence, expression of keratocyte unique keratan sulfated keratocan and lumican, and CD34. Moreover, umbilical mesenchymal stem cell transplantation improved host keratocyte functions, which was verified by enhanced expression of keratocan and aldehyde dehydrogenase class 3A1 in lumican null mice. Umbilical mesenchymal stem cell transplantation is a promising treatment for congenital corneal diseases involving keratocyte dysfunction. Unlike donated corneas, umbilical mesenchymal stem cells are easily isolated, expanded, stored, and can be quickly recovered from liquid nitrogen when a patient is in urgent need.
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