Weant Jessica, Eveleth David D, Subramaniam Amuthakannan, Jenkins-Eveleth Jennifer, Blaber Michael, Li Ling, Ornitz David M, Alimardanov Asaf, Broadt Trevor, Dong Hui, Vyas Vinay, Yang Xiaoyi, Bradshaw Ralph A
Trefoil Therapeutics, Inc, San Diego, CA, USA.
Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, USA.
Growth Factors. 2021 Feb-Jul;39(1-6):14-27. doi: 10.1080/08977194.2021.2012468. Epub 2021 Dec 9.
Utilising rabbit corneal endothelial cells (CEC) in three different paradigms, two human FGF1 derivatives (TTHX1001 and TTHX1114), engineered to exhibit greater stability, were tested as proliferative agents. Primary CECs and mouse NIH 3T3 cells treated with the two FGF1 derivatives showed equivalent EC ranges (3.3-24 vs.1.9-16. ng/mL) and, in organ culture, chemically lesioned corneas regained half of the lost endothelial layer in three days after treatment with the FGF1 derivatives as compared to controls. , following cryolesioning, the CEC monolayer, as judged by specular microscopy, regenerated 10-11 days faster when treated with TTHX1001. Over two weeks, all treated eyes showed clearing of opacity about twice that of untreated controls. In all three rabbit models, both FGF1 derivatives were effective in inducing CEC proliferation over control conditions, supporting the prediction that these stabilised FGF1 derivatives can potentially regenerate corneal endothelial deficits in humans.
利用三种不同范式下的兔角膜内皮细胞（CEC），对两种经过工程改造以表现出更高稳定性的人FGF1衍生物（TTHX1001和TTHX1114）作为增殖剂进行了测试。用这两种FGF1衍生物处理的原代CEC和小鼠NIH 3T3细胞显示出等效的内皮细胞范围（3.3 - 24对1.9 - 16 ng/mL），并且在器官培养中，与对照组相比，用FGF1衍生物处理三天后，化学损伤的角膜恢复了一半损失的内皮层。此外，在冷冻损伤后，通过镜面显微镜判断，用TTHX1001处理时CEC单层再生速度加快10 - 11天。在两周多的时间里，所有接受治疗的眼睛的混浊清除程度约为未治疗对照组的两倍。在所有三种兔模型中，两种FGF1衍生物在诱导CEC增殖方面均比对照条件更有效，支持了这些稳定的FGF1衍生物可能在人类中再生角膜内皮缺陷的预测。
