Research Institute of Clinical and Experimental Lymphology-Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 2 Timakova Str., 630060 Novosibirsk, Russia.
Novosibirsk Branch of S. Fedorov Eye Microsurgery Federal State Institution, 10 Kalkhidskaya Str., 630096 Novosibirsk, Russia.
Int J Mol Sci. 2023 May 16;24(10):8828. doi: 10.3390/ijms24108828.
Fibroblasts isolated and expanded from ReLEx SMILE lenticules can be a source of human keratocytes. Since corneal keratocytes are quiescent cells, it is difficult to expand them in vitro in suitable numbers for clinical and experimental use. In the present study, this problem was solved by isolating and growing corneal fibroblasts (CFs) with a high proliferative potential and their reversion to keratocytes in a selective serum-free medium. Fibroblasts reversed into keratocytes (rCFs) had a dendritic morphology and ultrastructural signs of activation of protein synthesis and metabolism. The cultivation of CFs in a medium with 10% FCS and their reversion into keratocytes was not accompanied by the induction of myofibroblasts. After reversion, the cells spontaneously formed spheroids and expressed keratocan and lumican markers, but not mesenchymal ones. The rCFs had low proliferative and migratory activity, and their conditioned medium contained a low level of VEGF. CF reversion was not accompanied by a change with the levels of IGF-1, TNF-alpha, SDF-1a, and sICAM-1. In the present study, it has been demonstrated that fibroblasts from ReLEx SMILE lenticules reverse into keratocytes in serum-free KGM, maintaining the morphology and functional properties of primary keratocytes. These keratocytes have a potential for tissue engineering and cell therapy of various corneal pathologies.
从 ReLEx SMILE 透镜中分离和扩增的成纤维细胞可以成为人角膜基质细胞的来源。由于角膜基质细胞是静止细胞,因此很难在体外以合适的数量进行扩增,以用于临床和实验用途。在本研究中,通过分离和培养具有高增殖潜能的角膜成纤维细胞(CFs)及其在无血清选择性培养基中向角膜基质细胞的逆转来解决了这个问题。逆转成角膜基质细胞(rCFs)的成纤维细胞具有树突状形态和蛋白质合成和代谢激活的超微结构迹象。CFs 在含有 10%FCS 的培养基中的培养及其向角膜基质细胞的逆转并没有伴随着肌成纤维细胞的诱导。逆转后,细胞自发形成球体并表达角膜蛋白聚糖和亮蛋白标志物,但不表达间充质标志物。rCFs 的增殖和迁移活性低,其条件培养基中含有低水平的 VEGF。CF 逆转并不伴随着 IGF-1、TNF-α、SDF-1a 和 sICAM-1 水平的变化。在本研究中,已经证明来自 ReLEx SMILE 透镜的成纤维细胞在无血清 KGM 中向角膜基质细胞逆转,保持原代角膜基质细胞的形态和功能特性。这些角膜基质细胞具有用于各种角膜病变的组织工程和细胞治疗的潜力。