Auto-mobilized adult hematopoietic stem cells advance neovasculature in diabetic retinopathy of mice

Chin Med J (Engl). 2010 Aug;123(16):2265-8.

Abstract

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.

Conclusion: Auto-mobilized adult hematopoietic stem cells advance neovasculature in diabetic retinopathy of mice.

MeSH terms

  • Animals
  • Diabetic Retinopathy / drug therapy*
  • Female
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Hematopoietic Cell Growth Factors / therapeutic use
  • Hematopoietic Stem Cell Mobilization / methods*
  • Humans
  • Immunohistochemistry
  • Mice
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism

Substances

  • Hematopoietic Cell Growth Factors
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Granulocyte Colony-Stimulating Factor