Cell Therapy of Congenital Corneal Diseases with Umbilical Mesenchymal Stem Cells: Lumican Null Mice

Abstract

BackgroundKeratoplasty is the most effective treatment for corneal blindness, but suboptimal medical conditions and lack of qualified medical personnel and donated cornea often prevent the performance of corneal transplantation in developing countries. Our study aims to develop alternative treatment regimens for congenital corneal diseases of genetic mutation.Methodology/Principal FindingsHuman mesenchymal stem cells isolated from neonatal umbilical cords were transplanted to treat thin and cloudy corneas of lumican null mice. Transplantation of umbilical mesenchymal stem cells significantly improved corneal transparency and increased stromal thickness of lumican null mice, but human umbilical hematopoietic stem cells failed to do the same. Further studies revealed that collagen lamellae were re-organized in corneal stroma of lumican null mice after mesenchymal stem cell transplantation. Transplanted umbilical mesenchymal stem cells survived in the mouse corneal stroma for more than 3 months with little or no graft rejection. In addition, these cells assumed a keratocyte phenotype, e.g., dendritic morphology, quiescence, expression of keratocyte unique keratan sulfated keratocan and lumican, and CD34. Moreover, umbilical mesenchymal stem cell transplantation improved host keratocyte functions, which was verified by enhanced expression of keratocan and aldehyde dehydrogenase class 3A1 in lumican null mice.Conclusions/SignificanceUmbilical mesenchymal stem cell transplantation is a promising treatment for congenital corneal diseases involving keratocyte dysfunction. Unlike donated corneas, umbilical mesenchymal stem cells are easily isolated, expanded, stored, and can be quickly recovered from liquid nitrogen when a patient is in urgent need.

Umbilical Cord Mesenchymal Stem Cells Suppress Host Rejection

“…Umbilical cord mesenchymal stem cell (UMSC) 2 transplantation successfully recovers corneal transparency and increased corneal thickness of lumican null mice (Lum Ϫ/Ϫ ) (1). Interestingly, these cells assume a keratocyte phenotype and promote collagen lamellae re-organization (1). We have also found that UMSCs transplanted into the corneal stroma of mice with the congenital metabolic disorder mucopolysaccharidosis VII impede progression of the stromal disease and improve corneal haze (2).…”

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

“…They also exhibited a dendritic morphology similar to that of natural keratocytes. Liu et al [57,58] reported that bone marrow-derived MSCs or umbilical MSCs transplanted into the cornea of keratocyte dysfunction mice significantly increased stromal thickness and improved corneal transparency and host keratocyte functions. These MSCs assumed corneal keratocyte phenotype and expressed the keratocyte-specific markers keratocan and lumican.…”

Corneal endothelium: developmental strategies for regeneration

“…The corneal transparency returned after 12 weeks with an increase of about 10% in stromal thickness, which was recorded after 8 weeks with no immune rejection. 100 In another study, a rabbit model for limbal stem cell deficiency was used to transplant bone marrow stem cells suspended in fibrin gel. 101 After 28 days, the corneas were completely epithelialized and transplanted stem cells expressed cytokeratin 3, a protein expressed by corneal epithelial cells.…”