Auto-mobilized adult hematopoietic stem cells advance neovasculature in diabetic retinopathy of mice.
BACKGROUND
Hematopoietic stem cells (HSCs) can be used to deliver functionally active angiostatic molecules to the retinal vasculature by targeting active astrocytes and may be useful in targeting pre-angiogenic retinal lesions. We sought to determine whether HSC mobilization can ameliorate early diabetic retinopathy in mice.


METHODS
Mice were devided into four groups: normal mice control group, normal mice HSC-mobilized group, diabetic mice control group and diabetic mice HSC mobilized group. Murine stem cell growth factor (murine SCF) and recombined human granulocyte colony stimulating factor (rhG-csf) were administered to the mice with diabetes and without diabetes for continuous 5 days to induce autologous HSCs mobilization, and subcutaneous injection of physiological saline was used as control. Immunohistochemical double staining was conducted with anti-mouse rat CD31 monoclonal antibody and anti-BrdU rat antibody.


RESULTS
Marked HSCs clearly increased after SCF plus G-csf-mobilization. Non-mobilized diabetic mice showed more HSCs than normal mice (P=0.032), and peripheral blood significantly increased in both diabetic and normal mice (P=0.000). Diabetic mice showed more CD31 positive capillary vessels (P=0.000) and accelerated endothelial cell regeneration. Only diabetic HSC-mobilized mice expressed both BrdU and CD31 antigens in the endothelial cells of new capillaries.


CONCLUSIONS
Auto-mobilized adult hematopoietic stem cells advance neovasculature in diabetic retinopathy of mice.
Tian
Bei
B
Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Science Key Laboratory, Beijing 100730, China.
Li
Xiao-xin
XX
Shen
Li
L
Zhao
Min
M
Yu
Wen-zhen
WZ
D000818:Animals; D003930:Diabetic Retinopathy / Q000188:drug therapy*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D016298:Hematopoietic Cell Growth Factors / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism
D016298:Hematopoietic Cell Growth Factors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D016179:Granulocyte Colony-Stimulating Factor