Khorolskaya Julia I, Perepletchikova Daria A, Kachkin Daniel V, Zhurenkov Kirill E, Alexander-Sinkler Elga I, Ivanova Julia S, Mikhailova Natalia A, Blinova Miralda I
Institute of Cytology Russian Academy of Science, 194064 St. Petersburg, Russia.
Laboratory of Amyloid Biology, St. Petersburg State University, 199034 St. Petersburg, Russia.
Biomedicines. 2021 Sep 1;9(9):1134. doi: 10.3390/biomedicines9091134.
The development of cell-based approaches to the treatment of various cornea pathologies, including limbal stem cell deficiency (LSCD), is an area of current interest in regenerative biomedicine. In this context, the shortage of donor material is urgent, and limbal mesenchymal stem cells (L-MSCs) may become a promising cell source for the development of these novel approaches, being established mainly within the rabbit model. In this study, we obtained and characterized rabbit L-MSCs and modified them with lentiviral transduction to express the green fluorescent protein EGFP (L-MSCs-EGFP). L-MSCs and L-MSCs-EGFP express not only stem cell markers specific for mesenchymal stem cells but also ABCG2, ABCB5, ALDH3A1, PAX6, and p63a specific for limbal epithelial stem cells (LESCs), as well as various cytokeratins (3/12, 15, 19). L-MSCs-EGFP have been proven to differentiate into adipogenic, osteogenic, and chondrogenic directions, as well as to transdifferentiate into epithelial cells. The possibility of using L-MSCs-EGFP to study the biocompatibility of various scaffolds developed to treat corneal pathologies was demonstrated. L-MSCs-EGFP may become a useful tool for studying regenerative processes occurring during the treatment of various corneal pathologies, including LSCD, with the use of cell-based technologies.
基于细胞的方法用于治疗包括角膜缘干细胞缺乏症(LSCD)在内的各种角膜病变,是再生生物医学当前关注的一个领域。在这种情况下,供体材料短缺的问题亟待解决,而角膜缘间充质干细胞(L-MSCs)可能成为开发这些新方法的一种有前景的细胞来源,目前主要是在兔模型中建立相关研究。在本研究中,我们获取并鉴定了兔L-MSCs,并通过慢病毒转导对其进行修饰以表达绿色荧光蛋白EGFP(L-MSCs-EGFP)。L-MSCs和L-MSCs-EGFP不仅表达间充质干细胞特有的干细胞标志物,还表达角膜缘上皮干细胞(LESCs)特有的ABCG2、ABCB5、ALDH3A1、PAX6和p63a,以及各种细胞角蛋白(3/12、15、19)。已证实L-MSCs-EGFP可向脂肪生成、成骨和成软骨方向分化,也可转分化为上皮细胞。研究证明了使用L-MSCs-EGFP来研究为治疗角膜病变而开发的各种支架的生物相容性的可能性。L-MSCs-EGFP可能成为研究在使用基于细胞的技术治疗包括LSCD在内的各种角膜病变过程中发生的再生过程的有用工具。