In this study, CD34-/low and Sca1+ were used as markers for early HSCs.3,13 The number of CD34-/low and Sca1+ cells in diabetic mice without mobilization was higher than in normal mice, indicating that the damage to vascular endothelial cells caused by diabetes activated HSCs. Combined use of SCF and G-csf could successfully mobilize both diabetic and normal mice to multiple the number of HSCs in periphery blood, indicating that diabetes had no influence on the mobilization of HSCs in periphery blood. CD31 was the marker for EPC.14 The KK mouse, an accepted model for diabetic retinopathy,15 demonstrates microangiopathies associated with diabetes and changes in the eye associated with pre-proliferative disease. In this study, we found the number of capillaries with CD31+ cells obviously increased in HSCs in KK mouse. This result demonstrates HSCs can promote hyperplasia in the EPC of diabetic mice. In normal mice with HSCs-mobilized, CD31+ cells increased over the control group, but were less than in diabetic mice control groups. This result demonstrates that, in hyperglycemia, more HSCs can differentiate to EPCs. It remains to be seen whether hyperglycemic damage to the vessel activates self renovation and mobilizes HSCs in peripheral blood.
Abnormal expression of factors related to angiogenesis (e.g. VEGF, ang-2, and others) and breakdown of the internal blood-retina barrier play an important role in the development of this disease. Other studies have shown fewer EPC in the peripheral blood of Types I and II diabetic patients, and decreased differentiation, adhesion and chemotaxis. The hypothesis has been put forward that diabetic microcirculation pathological changes result from EPC dysfunction.16,17 Many studies have proven that HSCs migrate from the bone marrow to peripheral blood, are differentiated into circulating EPCs (CEPs), go to damaged organs, then are differentiated into EPCs, developing into healthy vascular endothelial cells and forming vessels with normal functions during physiological angiogenesis.3,18 Seminal research by Otani et al13 proved the feasibility of treating ischemic diabetic retinopathy by repairing retinal blood vessels with HSCs. In this study, autologous mobilization increased the number of retinal capillaries with CD31 marker. Brdu was used as tracer for formation of new retinal blood vessels after autologous HSCs mobilization in diabetic mice. However, the retinal blood vessel may take one of two paths: to become a normal functional vessel, where the endodermis cell has tight, integrated connections; or to become an abnormal vessel which does not function normally. This study only proved that HSCs can advance vessel regrowth. Whether these vessels support improvements in diabetic retinopathy requires further study.
We thank Dr. LI Liao-qing for preparation of histologic samples, and Prof. LIU Xue-zong, Dr. ZHANG Jun and Dr. LU Ai-li for assistance.
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