Table 1 Subconjunctival injection of MSCs in experimental models of corneal epithelial damage
Species | Experimental model | Cell administration route | Follow-up time | Clinical signs | Cell migration | Anti-inflammatory/immunomodulatory effects | Corneal/limbal markers | Reference |
|---|---|---|---|---|---|---|---|---|
Mouse | Corneal and limbal mechanical removal in diabetic mice | Mouse BM-MSCs: one injection (5 × 104/5 μl PBS) immediately after damage | 24, 48, and 72 h | ↓Epithelial defect ↑Corneal epithelium proliferation | Migration to the limbal stroma and wound healing edge | ↓Inflammatory infiltrates ↓CD45, CD86 ↓M1: TNFα, MCP-1 ↑M2: CD206, IL-10, Arg-1 | ↑P63 ↓K12 | Di et al. [33] |
Corneal mechanical removal (2 mm trephine) | Mouse BM-MSCs: one injection (5 × 105/10 μl PBS) 1 h after damage | 2 and 4 days | ↓Epithelial defect ↓Corneal opacity | Migration to the cornea and conjunctiva | ↓CD45 ↓IL-1β, TNFα | – | Shukla et al. [62] | |
Rat | Corneal chemical burn (3 mm Ø disc/1 M NaOH 40s) | Rat BM-MSCs (2 injections 2 × 106/100 μl PBS): one immediately, and one 3 days after damage | 3–7 days | ↓Neovascularization ↓Epithelial defect ↑Corneal epithelium regeneration | No migration. Cells located in the injection site | ↓CD68 ↓MIP-1α, TNFα | – | Yao et al. [35] |
Corneal chemical burn (6 mm Ø disc/1 M NaOH 30s) | Rat BM-MSCs (2 injections 2 × 106/100 μl PBS + polysaccharide hydrogel): one immediately and one 2 days after damage | 3, 7, 14, and 28 days | ↓Neovascularization (↓VEGF and ↑TSP-1) ↑Corneal epithelium regeneration ↓Corneal opacity | – | ↓Inflammatory infiltrate ↑TGFβ ↓MIP-1α, TNFα | – | Ke et al. [36] | |
Corneal chemical burn (4 mm Ø disc/1 M NaOH 30s) | Human limbal MSCs: one injection (2.4 × 106/500 μl) 2 days after damage | 1, 2, 3, and 4 weeks | ↓Corneal opacity ↓Neovascularization ↓Epithelial defect | Migration to the corneal epithelium | ↓Inflammatory infiltrate | – | Acar et al. [63] | |
Corneal chemical burn (3 mm Ø disc/1 N NaOH 30s) | Rat BM-MSCs (1 × 106/100 μl PBS): one injection 7 days after damage | 7, 14, 21, and 28 days | ↑Corneal wound healing ↓Neovascularization (↓VEGF and MMP-9) ↓Epithelial defect ↓Corneal opacity | No migration. Cells located in the injection site | ↓Inflammatory infiltrate | – | Ghazaryan et al. [34] | |
Corneal/limbal chemical burn (3 mm Ø disc/1 M NaOH 40s) | Rat BM-MSCs: one injection (2 × 106/100 μl PBS) 3 days after damage | 3, 6, 9, and 12 days | ↓Corneal opacity ↓Neovascularization | – | – | – | Pan et al. [38] | |
Corneal chemical burn (6 mm Ø disc 1 N NaOH 20s) | Rat BM-MSCs (pre-stimulated with TNF-α and non-stimulated): one injection (2 × 106/100 μl PBS) immediately after damage | 3, 7, and 14 days | ↓Corneal opacity ↓Epithelial defect | No migration. Cells located in the injection site | ↓Inflammatory infiltrates ↓CD68 ↓iNOS, TNFα, IL-1, IL-6, MCP-1, MIP-1α ↑PTGS2, TSG-6 | – | Zhang et al. [64] | |
Rabbit | Corneal chemical burn (7 mm Ø disc/10% NaOH 40s) | Human AT-MSCs (1.3 × 105/200 μl saline solution): one injection immediately after damage | 30 days | ↓Epithelial defect ↓Corneal opacity | – | – | ↑Connexin-43 ↑β-catenin No changes in E-cadherin and p63 | Lin et al. [37] |
Corneal chemical burn (6 mm Ø disc 1 N NaOH 30s on the upper cornea) | Combined administration: AT-MSCs (2 × 106/500 μl) from rabbit by topical administration + stromal pocket + subconjunctival injection (immediately after injury) | 3, 7, 14, 21, and 28 days | ↓Corneal opacity ↓Neovascularization (↓VEGF) ↓Epithelial defect | – | ↓Inflammation | – | Almaliotis et al. [65] | |
Partial corneal/limbal chemical burn (4 mm Ø disc/1 M KOH 30s) | Human BM-MSCs or human limbal MSCs: one injection (5 × 103/200 μl) immediately after damage | 7, 14, 28 days, and 3 months | ↓Corneal opacity ↓Neovascularization ↓Epithelial defect ↓Goblet cells in the cornea | Human limbal MSC: migration to the cornea | – | – | Li et al. [39] |