Bone marrow-derived progenitor cells promote corneal wound healing following alkali injury.
OBJECTIVE
To determine whether bone marrow-derived progenitor cells can be stimulated by inflammatory mediators and play a role in corneal wound healing following alkali injury.


METHODS
Sixty rabbits were divided into two groups (Group I and Group II). Group I served as a bone marrow-suppression model, and received 200 mg/kg cyclophosphamide. Corneal alkali injury was created in one eye of each rabbit in each group; the other eye served as control. Three days after corneal burn, inflammatory cells in peripheral blood were counted. At the end of 4 weeks follow-up, corneas of all rabbits were subjected to histochemical examination to assess infiltrated CD34 and C-kit positive cells. Clinical outcome was determined at the end of 4 weeks.


RESULTS
Cyclophosphamide suppressed bone marrow function in Group I by reducing cellularity by more than 30% and neutrophil distribution by 3.18 +/- 1.83%. The number of bone marrow hematopoietic and mesenchymal progenitor cells were all suppressed by cyclophophamide, as demonstrated by statistically significant differences between Group I and Group II of CD34+ cells (t = -21.62, P < 0.01) and C-Kit cells (t = -21.62, P < 0.01). Fewer inflammatory cells were released into circulation in Group I (14.42 +/- 5.70%) than in Group II (44.36 +/- 8.64%). Clinical observation revealed that Group II rabbits had much greater reepithelization (t = 6.999, P < 0.01) and clearer corneas (X(2) = 4.417, P < 0.01) than Group I.


CONCLUSIONS
Corneal alkali injury is a stimulus that induces a rapid bone marrow reaction to release not only inflammatory cells but also progenitor cells into circulation. Migrated bone marrow-derived progenitor cells can home to local sites to promote wound healing.
Ye
Juan
J
Department of Ophthalmology, The 2nd Affiliated Hospital of Zhejiang University, College of Medicine, Hangzhou, Zhejiang, China. YeJuan_99@yahoo.com.cn
Lee
Sang Yeul
SY
Kook
Koung Hoon
KH
Yao
Ke
K
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology*; D002057:Burns, Chemical / Q000378:metabolism* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D019573:Epithelium, Corneal / Q000502:physiology*; D005126:Eye Burns / Q000139:chemically induced* / Q000473:pathology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D007124:Immunoenzyme Techniques; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011817:Rabbits; D012972:Sodium Hydroxide; D014945:Wound Healing / Q000502:physiology*
D018952:Antigens, CD34; D007166:Immunosuppressive Agents; D012972:Sodium Hydroxide; D003520:Cyclophosphamide; D019009:Proto-Oncogene Proteins c-kit