Stem Cell Therapy Restores Transparency to Defective Murine Corneas

Abstract

Corneal scarring from trauma and inflammation disrupts vision for millions worldwide, but corneal transplantation, the primary therapy for corneal blindness, is unavailable to many affected individuals. In this study, stem cells isolated from adult human corneal stroma were examined for the ability to correct stromal opacity in a murine model by direct injection of cells into the corneal stroma. In wild-type mice, injected human stem cells remained viable for months without fusing with host cells or eliciting an immune T-cell response. Human corneal-specific extracellular matrix, including the proteoglycans lumican and keratocan, accumulated in the treated corneas. Lumican-null mice have corneal opacity similar to that of scar tissue as a result of disruption of stromal collagen organization. After injection with human stromal stem cells, stromal thickness and collagen fibril defects in these mice were restored to that of normal mice. Corneal transparency in the treated mice was indistinguishable from that of wild-type mice. These results support the immune privilege of adult stem cells and the ability of stem cell therapy to regenerate tissue in a manner analogous to organogenesis and clearly different from that of normal wound healing. The results suggest that cell-based therapy can be an effective approach to treatment of human corneal blindness.

Stem Cells in the Trabecular Meshwork for Regulating Intraocular Pressure

“…We also elucidated the pathological changes responsible for the change of outflow and the elevation of IOP. Previously, we discovered that adult corneal stromal stem cells have an ability to remodel tissue matrix in vivo 70 and TM stem cells can selectively home to TM region in vivo. 71 We hypothesize that homed TM stem cells, like corneal stromal stem cells, can remodel tissue matrix in vivo to promote TM extracellular matrix turnover and maintain TM homeostasis.…”

Mesenchymal stem cells: Potential role in corneal wound repair and transplantation

“…Niche stromal cells might provide a specialized microenvironment for the maintenance of LSCs [30] . In addition, corneal limbal stromal cells possess immune privileged [34] and immunosuppressive properties. Limbal MSCs can suppress T cell proliferation by constitutively secreting transforming growth factor-β1 (TGF-β1) [35] .…”

Postnatal periodontal ligament as a novel adult stem cell source for regenerative corneal cell therapy

“…These cells can further transform into highly contractile myofibroblasts (under the action by TGFβ and platelet‐derived growth factor) that are shown to associate with corneal haze development and scar formation 62, 63. Human corneal stromal stem cells (CSSCs) identified from limbal stroma have offered an opportunity to develop functional CSKs through population doublings and produce stroma‐like ECM 64. Future identification of unique markers will help in a more efficient isolation of pure CSSCs and a better control of differentiation 65, 66.…”