Wnt activation as a potential therapeutic approach to treat partial limbal stem cell deficiency.
Wnt activation as a potential therapeutic approach to treat partial limbal stem cell deficiency.
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DOI：
10.1038/s41598-023-42794-8
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发表时间：
2023-09-21
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
角膜缘上皮干/祖细胞（LSC）是位于利姆布斯的成体干细胞，受其涉及许多信号通路（如Wnt）的小生境的严格调控。Wnt蛋白是一种分泌型形态发生蛋白，在胚胎发育、干细胞增殖、自我更新、组织再生和成人重塑中发挥关键作用。已经显示，小分子Wnt模拟物可以改善离体LSC扩增。对LSC和/或其生态位的损伤可导致角膜缘干细胞缺乏症（LSCD），这是一种可导致角膜失明且难以治疗的疾病。本研究探讨了通过Wnt激活在部分LSCD中重新填充残余LSC是否可能是一种新的治疗方法。为了模拟由于化学损伤引起的LSCD，将单个培养的LSC暴露于各种浓度的氢氧化钠。观察到LSC表型的进行性丧失：p63亮细胞和细胞角蛋白（K）14+细胞的百分比下降，而K12+细胞的百分比增加。通过分别用氯化锂（LiCl）和小分子Wnt模拟物处理LSC来实现Wnt活化。处理18 h后，LSC增殖增加，LSC表型恢复，而未处理的细胞不增殖并失去其表型。与未处理的细胞相比，Wnt模拟物处理的细胞中p63bright细胞的百分比显著增加，而K12+细胞的百分比显著降低。这些发现表明，局部Wnt激活可能会在碱性损伤后拯救LSC。
Limbal epithelial stem/progenitor cells (LSCs) are adult stem cells located at the limbus, tightly regulated by their niche involving numerous signaling pathways, such as Wnt. Wnt proteins are secreted morphogens that play critical roles in embryonic development, stem cell proliferation, self-renewal, tissue regeneration, and remodeling in adults. It has been shown that a small molecule Wnt mimic could improve LSCs expansion ex vivo. Damage to the LSCs and/or their niche can lead to limbal stem cell deficiency (LSCD), a condition that can cause corneal blindness and is difficult to treat. This study explored if repopulating residual LSCs in partial LSCD through Wnt activation could be a novel therapeutic approach. To mimic LSCD due to a chemical injury, single cultured LSCs were exposed to various concentrations of sodium hydroxide. A progressive loss of the LSCs phenotype was observed: the percentage of p63bright cells and cytokeratin (K)14+ cells decreased while the percentage of K12+ increased. Wnt activation was attained by treating the LSCs with lithium chloride (LiCl) and a small-molecule Wnt mimic, respectively. After 18 h of treatment, LSCs proliferation was increased, and the LSCs phenotype was recovered, while the untreated cells did not proliferate and lost their phenotype. The percentage of p63bright cells was significantly higher in the Wnt mimic-treated cells compared with untreated cells, while the percentage of K12+ cells was significantly lower. These findings suggest that local Wnt activation may rescue LSCs upon alkaline injury.
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DOI：
10.1089/ten.tec.2016.0388
发表时间：
2017-04
期刊：
Tissue engineering. Part C, Methods
影响因子：
--
作者：
González S;Chen L;Deng SX
通讯作者：
Deng SX
影响因子：
2.8
作者：
通讯作者：
--
影响因子：
3.4
作者：
Bonnet C;Roberts JS;Deng SX
通讯作者：
Deng SX
影响因子：
4.6
作者：
Bonnet C;Oh D;Mei H;Robertson S;Chang D;Bourges JL;Behar-Cohen F;Zheng JJ;Deng SX
通讯作者：
Deng SX
影响因子：
2.8
作者：
Goswami, Dinesh G.;Tewari-Singh, Neera;Agarwal, Rajesh
通讯作者：
Agarwal, Rajesh