Mesenchymal stem cell transplantation in a rabbit corneal alkali burn model: engraftment and involvement in wound healing.
OBJECTIVE
To investigate whether systemically transplanted mesenchymal stem cells (MSCs) can home and engraft in tissue to promote cornea wound healing after alkali burn, as a new source for treatment.


METHODS
Corneal alkali burn was created in four group rabbits: Group I, normal bone marrow function, without MSCs transplantation; Group II, normal bone marrow function, with MSCs transplantation; Group III, bone marrow suppressed by cyclophosphamide, without MSCs; Group IV, bone marrow suppressed by cyclophosphamide, with MSCs. Clinical outcome was evaluated by cornea re-epithelization, cornea opacity, and neovascularization. Cell engraftment into bone marrow, circulation, and cornea was monitored. Immunohistochemistry, using proliferating cell nuclear antigen (PCNA), P63, vimentin, and alpha-smooth muscle actin (alpha-SMA) was carried out to assess the cell proliferative and differentiative ability.


RESULTS
At the time of 1-month follow-up, Group II rabbits showed the best clinical results with a clearer healed cornea compared with other groups. Well-formed neovascularization appeared on day 14 after alkali burn in Group II, that coincided with the maximum engraftment of MSCs. PCNA, P63, vimentin were more strongly expressed in Group II at multiple time points. DiI-labelled MSCs were differentiated into myofibroblast by the expression of alpha-SMA. Delayed and insufficient cell engraftment, with malformed neovascularization and retarded corneal wound healing was found in Groups III and IV.


CONCLUSIONS
Systemically transplanted MSCs can engraft to injured cornea to promote wound healing, by differentiation, proliferation, and synergizing with haemotopoietic stem cells.
Ye
J
J
Eye Center, 2nd Affiliated Hospital of Zhejiang University, College of Medicine, Hangzhou, Zhejiang, China. YeJuan_99@yahoo.com.au
Yao
K
K
Kim
J C
JC
D000468:Alkalies; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002057:Burns, Chemical / Q000473:pathology / Q000628:therapy*; D002454:Cell Differentiation; D049109:Cell Proliferation; D003315:Cornea / Q000098:blood supply / Q000473:pathology; D003520:Cyclophosphamide / Q000494:pharmacology; D004195:Disease Models, Animal; D005126:Eye Burns / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D006085:Graft Survival; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D018919:Neovascularization, Physiologic; D011817:Rabbits; D014945:Wound Healing
D000468:Alkalies; D003520:Cyclophosphamide