Cell therapy of congenital corneal diseases with umbilical mesenchymal stem cells: lumican null mice.
BACKGROUND
Keratoplasty 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.


RESULTS
Human 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
Umbilical 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.
Liu
Hongshan
H
Department of Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States of America.
Zhang
Jianhua
J
Liu
Chia-Yang
CY
Wang
I-Jong
IJ
Sieber
Martin
M
Chang
John
J
Jester
James V
JV
Kao
Winston W Y
WW
D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D002469:Cell Separation; D048430:Cell Shape; D002470:Cell Survival; D011508:Chondroitin Sulfate Proteoglycans / Q000172:deficiency* / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D003316:Corneal Diseases / Q000151:congenital* / Q000473:pathology / Q000628:therapy*; D003713:Dendritic Cells / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D007632:Keratan Sulfate / Q000172:deficiency* / Q000378:metabolism; D000071234:Lumican; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D011509:Proteoglycans / Q000378:metabolism; D017154:Stromal Cells / Q000473:pathology / Q000637:transplantation; D014470:Umbilical Cord / Q000166:cytology*; D015854:Up-Regulation
D000444:Aldehyde Dehydrogenase; D015415:Biomarkers; D011508:Chondroitin Sulfate Proteoglycans; D003094:Collagen; D007632:Keratan Sulfate; D000071234:Lumican; D011509:Proteoglycans; C099280:Kera protein, mouse; C000604306:LUM protein, human; C000604307:Lum protein, mouse; C105543:Aldh3a1 protein, mouse