Abstract 14888: Restoration of Krúppel-Like Factor 2 Expression by Oxytocin Facilitates Angiogenesis in Diabetes-Insulted Mesenchymal Stem Cells
Objective: The aim of this study is to examine whether the impaired function of diabetes-exposed stem cells is recovered by oxytocin with regard to Krüppel-like factor 2 (KLF2), a transcription factor critical in endothelial function.
Background: Angiogenesis is the main therapeutic mechanism of stem cell therapy for cardiovascular diseases, but diabetes is reported to reduce the function and number of progenitor cells.
Methods: Bone marrow cells (BMCs) were isolated from streptozotocin-induced diabetic rat or healthy rat. BMCs were treated with vehicle or oxytocin (100 nM) prior to experiments. Angiogenic activity was measured by Boyden chamber assay and Matrigel plug assay. KLF2 levels were measured by RT-PCR and Western blot. Mouse hind limb ischemia was induced by ligation of the femoral artery, and groups of mice received local injection of phosphate-buffered saline (Group 1), non-DM-BMSCs (Group 2), DM-BMSCs (Group 3), or oxytocin-treated DM-BMSCs (Group 4). Blood flow was assessed by laser Doppler imaging and ischemic muscle was harvested for assessment of capillary density..
Results: In Boyden chamber assay, tube length and tube area were severely low in DM-BMSCs, which were significantly recovered by oxytocin treatment. The mRNA and protein of KLF2 was dramatically reduced in DM-BMSCs but were restored by oxytocin. In the Matrigel plug assay, vessel formation of DM-BMSCs was attenuated but was recovered by oxytocin. Compared with that in the PBS-injected group, perfusion was recovered 2.52-fold in the non-DM-BMSCs group, whereas it was recovered 1.47-fold in the DM-BMSCs group. Hind limb perfusion in the oxytocin-treated DM-BMSCs group was 3.9-fold that in the DM-BMSCs group. To confirm the pro-angiogenic role of KLF2 in BMCs, KLF2 was transfected into DM-BMSCs and tube formation was significantly recovered.
Conclusion: Our results showed that DM-BMSCs were functionally impaired with lowered KLF2 and would result in insufficient outcomes in stem cell therapy. We demonstrated the striking effect of oxytocin on stem cell dysfunction and suggest oxytocin as a priming reagent in autologous stem cell therapy.
- © 2012 by American Heart Association, Inc.