School of Medicine, Nankai University, Tianjin, People's Republic of China.
Department of Ophthalmology, The Third Medical Center of Chinese People's Liberation Army General Hospital, Beijing, People's Republic of China.
Stem Cells. 2023 Jun 15;41(6):592-602. doi: 10.1093/stmcls/sxad027.
Corneal alkali burns cause extensive damage not only to the cornea but also to the intraocular tissues. As an anti-inflammatory therapy, subconjunctival administration of mesenchymal stem cells (MSCs) for corneal protection after corneal alkali burn has been explored. Little evidence demonstrates the potential of subconjunctival MSCs delivery in protecting the post-burn intraocular tissues. This study aimed to evaluate the therapeutic efficacy of subconjunctival injection of human placental (hP)-MSCs in protecting against ocular destruction after the burn. hP-MSCs were subconjunctivally administered to C57/BL mice after corneal alkali burn. Western blot of iNOS and CD206 was performed to determine the M1 and M2 macrophage infiltration in the cornea. Infiltration of inflammatory cells in the anterior uvea and retina was analyzed by flow cytometry. The TUNEL assay or Western blot of Bax and Bcl2 was used to evaluate the anti-apoptotic effects of MSCs. MSCs could effectively facilitate cornea repair by suppressing inflammatory cytokines IL-1β, MCP-1, and MMP9, and polarizing CD206 positive M2 macrophages. Anterior uveal and retinal inflammatory cytokines expression and inflammatory cell infiltration were inhibited in the MSC-treated group. Reduced TUNEL positive staining and Bax/Bcl2 ratio indicated the anti-apoptosis of MSCs. MSC-conditioned medium promoted human corneal epithelial cell proliferation and regulated LPS-stimulated inflammation in RAW 264.7 macrophages, confirming the trophic and immunoregulatory effects of MSCs. Our findings demonstrate that subconjunctival administration of MSCs exerted anti-inflammatory and anti-apoptotic effects in the cornea, anterior uvea, and retina after corneal alkali burn. This strategy may provide a new direction for preventing post-event complications after corneal alkali burn.
角膜碱烧伤不仅会对角膜造成广泛损伤，还会对眼内组织造成损伤。间充质干细胞（MSCs）作为一种抗炎治疗方法，已被探索用于角膜碱烧伤后的角膜保护。很少有证据表明结膜下注射 MSCs 传递在保护烧伤后眼内组织方面的潜力。本研究旨在评估结膜下注射人胎盘（hP）-MSCs 对预防烧伤后眼破坏的治疗效果。在角膜碱烧伤后，将 hP-MSCs 结膜下注射到 C57/BL 小鼠中。通过 Western blot 检测 iNOS 和 CD206 以确定角膜中 M1 和 M2 巨噬细胞的浸润。通过流式细胞术分析眼前段和视网膜中炎症细胞的浸润。TUNEL 检测或 Bax 和 Bcl2 的 Western blot 用于评估 MSC 的抗凋亡作用。MSCs 可以通过抑制炎症细胞因子 IL-1β、MCP-1 和 MMP9，并使 CD206 阳性的 M2 巨噬细胞极化，有效地促进角膜修复。在 MSC 处理组中，抑制了前葡萄膜炎和视网膜中炎症细胞因子的表达和炎症细胞浸润。减少的 TUNEL 阳性染色和 Bax/Bcl2 比值表明 MSC 的抗凋亡作用。MSC 条件培养基促进人角膜上皮细胞的增殖，并调节 LPS 刺激的 RAW 264.7 巨噬细胞中的炎症，证实了 MSCs 的营养和免疫调节作用。我们的研究结果表明，结膜下注射 MSCs 可在角膜碱烧伤后对角膜、眼前段和视网膜发挥抗炎和抗凋亡作用。这种策略可能为预防角膜碱烧伤后事件相关并发症提供新的方向。
