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H. Liu, J. V. Jester, M. Sieber, J. Chang, C.-Y. Liu, W. W. Kao; Human Mesenchymal Stem Cells Differentiate Into Keratocytes in the Mouse Cornea. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4519.
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© ARVO (1962-2015); The Authors (2016-present)
Mesenchymal stem cells (MSC) have been studied for their potential use of reparative strategies in various tissues. Herein, we examined whether human umbilical cord MSC can differentiate to express keratocan and lumican when they were transplanted into the corneal stroma of Kera-/- and Lum-/- mice.
MSC and hematopoietic stem cells (HSC) obtained from human umbilical cord were labeled by DIO in vitro, and then intrastromally injected into corneas of Kera-/- and Lum-/- mice. Morphological changes of human umbilical cord-derived cells in the cornea were examined by fluorescent stereomicroscopy. Mouse corneas were examined by HRTII for thickness. Immunohistochemistry and western blot analysis with anti-keratocan and anti-lumican antibodies were used to detect the expression of keratocan and lumican in the recipient mice.
Immunostaining confirmed that MSC and HSC were negative for both keratocan and lumican before the transplantation. One week after intrastromal injection, MSC and HSC changed shape to assume dendritic morphology. The number of transplanted HSC reduced by 80.4% (n=8) after five weeks of HSC injection in comparison to that of one week after injection of HSC; whereas 43.5% (n=10) of transplanted MSC remained. Imunostaining and western blot revealed that keratocan and lumican were present in the extracellular matrix of stroma of Kera-/- and Lum-/- mice one week after receiving MSC transplant, respectively. On the other hand, HSC transplanted cells did not appear to express either keratocan or lumican in the experimental mouse corneas. Moreover, immunostaining with anti-CD45, CD90, and F4/80 antibodies indicated that many leukocytes, T-cells, and macrophages of recipient origin appeared in corneal stroma of Kera-/- mice after the injection of HSC, suggesting graft rejection caused by HSC transplantation; in contrast few inflammatory cells were detected following MSC transplantation. In Lum-/- mice, transplantation of MSC caused a slight increase of corneal stroma thickness by 4.86±3.76 µm (average of increase ± standard deviation, P = 0.014, n=7).
MSC transplanted into the mouse cornea may differentiate to a keratocyte phenotype and express keratocan and lumican. These findings suggest that MSC transplantation may be a potential treatment strategy for certain genetic and/or acquired corneal diseases.
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