Transplantation of human umbilical mesenchymal stem cells cures the corneal defects of mucopolysaccharidosis VII mice.
Transplantation of human umbilical mesenchymal stem cells cures the corneal defects of mucopolysaccharidosis VII mice.
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DOI：
10.1002/stem.1481
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发表时间：
2013-10
期刊：
影响因子：
5.2
通讯作者：
Kao, Winston W-Y.
中科院分区：
文献类型：
--
作者：
Coulson-Thomas, Vivien Jane;Caterson, Bruce;Kao, Winston W-Y.
粘多糖症(MPS)是由溶酶体外切糖苷酶突变导致糖胺多聚糖(GAG)积聚引起的一系列相关疾病。MPS VII由β-葡萄糖苷酸酶突变引起，表现为肝脏肿大、骨骼发育不良、身材矮小、角膜混浊和发育迟缓。目前治疗MPS的治疗方案对治疗角膜混浊和智力发育障碍无效。我们推测，移植到角膜基质中的人脐静脉间充质干细胞(UMSC)可以参与GAG的分解代谢，为MPS的细胞治疗提供了一种手段。为了进行这种治疗，将人UMSC移植到MPS VII小鼠的角膜中。UMSC移植分别恢复了宿主角膜基质细胞和内皮细胞的树突状和六角形形态，体内共聚焦显微镜(HRTII)显示角膜混浊减少。用HS和CS链抗体以及LAMP2的免疫组织化学显示，治疗后的角膜中GAG含量减少，溶酶体的数量和大小都减少了。移植前标记UMSC胞内室显示UMSC囊泡分布于角膜基质和内皮细胞。从MPSVII小鼠分离的皮肤成纤维细胞与UMSC的体外共培养实验表明，UMSC释放的中性囊泡被成纤维细胞摄取并与酸性溶酶体融合。因此，移植的UMSC既参与了细胞外GAG的代谢，又能使宿主角膜基质细胞降解积聚的GAG产物，提示UMSC可能成为治疗MPS和其他先天性代谢紊乱相关的角膜缺损的一种新的选择。
Mucopolysaccharidosis (MPS) are a family of related disorders caused by a mutation in one of the lysosomal exoglycosidases which leads to the accumulation of glycosaminoglycans (GAGs). MPS VII, caused by a mutation in β-glucuronidase, manifests hepatomegaly, skeletal dysplasia, short stature, corneal clouding and developmental delay. Current treatment regimens for MPS are not effective for treating corneal clouding and impaired mental development. We hypothesized that human umbilical mesenchymal stem cells (UMSC) transplanted into the corneal stroma could participate in the catabolism of GAGs providing a means of cell therapy for MPS. For such treatment, human UMSC were intrastromally transplanted into corneas of MPS VII mice. UMSC transplantation restored the dendritic and hexagonal morphology of host keratocytes and endothelial cells, respectively, and in vivo confocal microscopy (HRTII) revealed reduced corneal haze. Immunohistochemistry using antibodies against HS and CS chains as well as LAMP2 revealed a decrease in GAG content and both lysosomal number and size in the treated corneas. Labeling UMSC intracellular compartments prior to transplantation revealed the distribution of UMSC vesicles throughout the corneal stroma and endothelium. An in vitro co-culture assay between skin fibroblasts isolated from MPSVII mice and UMSC demonstrated that neutral vesicles released by the UMSC are taken up by the fibroblasts and proceed to fuse with the acidic lysosomes. Therefore, transplanted UMSC participate both in extracellular GAG turnover and enable host keratocytes to catabolize accumulated GAG products, suggesting that UMSC could be a novel alternative for treating corneal defects associated with MPS and other congenital metabolic disorders.
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影响因子：
3.8
作者：
Rowan, Daniel J.;Tomatsu, Shunji;Sly, William S.
通讯作者：
Sly, William S.
DOI：
10.1111/j.1749-6632.1971.tb46934.x
发表时间：
1971-01-01
影响因子：
5.2
作者：
NEUFELD, EF;CANTZ, MJ
通讯作者：
CANTZ, MJ
影响因子：
3
作者：
Kao, WWY;Liu, CY
通讯作者：
Liu, CY
影响因子：
3.7
作者：
Liu H;Ren G;Miao Z;Zhang X;Tang X;Han P;Gambhir SS;Cheng Z
通讯作者：
Cheng Z
影响因子：
7.5
作者：
Kadler KE;Hill A;Canty-Laird EG
通讯作者：
Canty-Laird EG