权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Investigation on neural and ocular surface regeneration after cultivated mucosal epithelial sheet transplantation using amniotic membrane

羊膜培养粘膜上皮片移植后神经及眼表再生的研究

基本信息

批准号：
18591931
负责人：
INATOMI Tsutomu
金额：
$ 2.57万
依托单位：
Kyoto Prefectural University of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

Cultivated mucosal epithelial transplantation using corneal epithelial stem cells and oral mucosal epithelium dramatically improves the clinical outcome of severe ocular surface reconstruction. However, the biological mechanisms behind the cell proliferation and differentiation still remain unclear. In this study, the in vivo condition of the regenerated tissue structure composed of transplanted epithelium was investigated using in vivo laser confocal microscopy. The surviving oral mucosal epithelium showed a well-differentiated, stratified epithelial structure similar to corneal epithelium. The high density and large number of basal cells indicated the active potential for cell proliferation to maintain the ocular surface. No neural regeneration was observed in the epithelial cell layer and sub-amniotic membrane region even after an extended period of time. This evidence is consistent with the low amount of ocular surface sensation.Oral mucosal stem- and progenitor cells expressed p75 that exhibited a high affinity with neurotrophin, indicating that surviving oral mucosal epithelium may be regulated by nerve growth factor (NGF) and neurotrophin 3 and 4. Differentiated oral mucosal epithelium on the ocular surface does not express keratin 1 and 4, keratins that are specific for keratinization, but does express keratin 3 and 13. Surviving oral mucosal epithelium does not express keratin 12 that is cornea specific or MUCSAC that is specific for goblet cells. This study concluded that surviving oral mucosal epithelium on the ocular surface is able to retain the oral mucosal epithelial lineage without transdifferentiation into ocular surface epithelium.

使用角膜上皮干细胞和口腔粘膜上皮培养的粘膜上皮移植显著改善了严重眼表重建的临床结果。然而，细胞增殖和分化背后的生物学机制仍不清楚。本研究利用体内激光共聚焦显微镜研究了由移植上皮构成的再生组织结构的体内条件。存活的口腔黏膜上皮显示出分化良好的复层上皮结构，类似于角膜上皮。基底层细胞密度高，数量多，提示细胞增殖活跃，维持眼表功能。即使在较长的时间后，仍未观察到上皮细胞层和羊膜下区域的神经再生。口腔黏膜干/祖细胞表达与神经营养因子高度亲和力的p75，提示存活的口腔黏膜上皮可能受神经生长因子(NGF)和神经营养因子3、4的调节。分化后的口腔黏膜上皮不表达角蛋白1和4，角蛋白3和13是角化所特有的，但表达角蛋白3和13。存活的口腔粘膜上皮不表达角蛋白12(角蛋白12)或MUCSAC(杯状细胞特异性)。这项研究的结论是，存活在眼表上的口腔粘膜上皮能够保留口腔黏膜上皮的谱系，而不会转分化为眼表上皮。