Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA; Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Eye Research Center, The Five Senses Health Institute, Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.
Ocul Surf. 2023 Oct;30:187-195. doi: 10.1016/j.jtos.2023.09.008. Epub 2023 Sep 25.
Different approaches to delivery of mesenchymal stem/stromal cells (MSCs) for ameliorating corneal injuries have been investigated. This study was aimed to compare the efficacy of intrastromal and subconjunctival injection of human bone marrow-derived MSCs (hBM-MSCs) in a corneal epithelial injury model.
Twenty-four C57BL/6J mice underwent total corneal and limbal epithelial debridement. Then, the mice were divided into three different groups: (1) intrastromal hBM-MSCs injection, (2) subconjunctival hBM-MSCs injection, and (3) injection of frozen medium as a control. Mice were monitored by slit lamp and underwent anterior segment optical coherence tomography (ASOCT). Following euthanasia, the corneas were further evaluated by histology and immunostaining.
hBM-MSC injection successfully healed epithelial defects regardless of the delivery route (P < 0.001). However, intrastromal injection was superior to subconjunctival injection in reducing defect area (P = 0.001). Intrastromal injection of hBM-MSCs also significantly reduced corneal opacity and neovascularization and improved ASOCT parameters compared to subconjunctival injection or no treatment (P < 0.001, P = 0.003, and P < 0.001, respectively). Although both of the treatment groups were positive for CK12 and had reduced levels of MUC5AC compared to the control, CK12 staining was stronger in the intrastromal group compared to the subconjunctival group. Also, persistency of MSCs was confirmed by in vivo (up to 2 weeks) and in vitro assessments (up to 4 weeks).
Although the injection of hBM-MSC using both intrastromal and subconjunctival methods improve wound healing and reduce neovascularization and opacity, the intrastromal approach is superior in terms of corneal healing.
为了改善角膜损伤，人们已经研究了多种间充质干细胞（MSCs）的递送方法。本研究旨在比较骨髓间充质干细胞（hBM-MSCs）经角膜基质内和结膜下注射治疗角膜上皮损伤模型的疗效。
24 只 C57BL/6J 小鼠接受全角膜和角膜缘上皮清创术。然后，将小鼠分为三组：（1）角膜基质内注射 hBM-MSCs，（2）结膜下注射 hBM-MSCs，（3）注射冷冻培养基作为对照。通过裂隙灯和眼前节光学相干断层扫描（ASOCT）对小鼠进行监测。安乐死后，进一步通过组织学和免疫染色评估角膜。
无论递送途径如何，hBM-MSC 注射均成功治愈上皮缺损（P<0.001）。然而，与结膜下注射相比，角膜基质内注射在减少缺损面积方面更具优势（P=0.001）。与结膜下注射或不治疗相比，角膜基质内注射 hBM-MSCs 还显著降低了角膜混浊和新生血管形成，并改善了 ASOCT 参数（P<0.001，P=0.003 和 P<0.001）。尽管两组治疗组的 CK12 均呈阳性，且与对照组相比 MUC5AC 水平降低，但角膜基质内组的 CK12 染色强于结膜下组。此外，体内（长达 2 周）和体外评估（长达 4 周）均证实了 MSCs 的持续性。
虽然通过角膜基质内和结膜下注射 hBM-MSC 均可改善伤口愈合并减少新生血管形成和混浊，但在角膜愈合方面，角膜基质内注射方法更具优势。
