Abstract 17100: Priming with Erythropoietin Enhances Survival and Pro-Angiogenic Properties in Mesenchymal Stem Cells
Introduction: Accumulating evidence from animal studies shows that the administration of mesenchymal stem cells (MSCs) from bone marrow ameliorates tissue damage after ischemic injury. However, the inability to effectively graft culture-expanded stem cells to diseased or injured tissues remains a challenge for cell therapy. Erythropoietin (Epo) is an erythropoiesis-stimulating cytokine and protects erythroid progenitors from cell death. Epo receptor was identified in MSCs, but the action of Epo/Epo receptor signaling is not determined. In the present study we investigated whether Epo enhanced the survival and pro-angiogenic potential in the MCSs in both culture and animal experiments.
Methods and Results: Epo receptor was expressed on MSCs isolated from bone marrow in GFP-transgenic rats. In culture study, the Epo treatment (80IU/ml) significantly propagated the MSCs compared with the controls (2-fold increase, p<0.05). Quantitative RT-PCR analysis demonstrated that Epo significantly enhanced the expressions of basic-fibroblast growth factor and stromal cell-derived factor-1 in the cultured MSCs. In vivo, the GFP-MSCs preconditioned with and without Epo (80IU/ml) for 48 hours were locally administered to rat hindlimb ischemia model (n=11 in each group). Priming with Epo significantly increased the MSC engraftment in perivascular area of the injured muscle at day 3 after the implantation more than without Epo (1.5±1.3 vs. 3.0±2.1, p<0.05). The MSCs preconditioned with Epo significantly promoted blood perfusion documented by laser Doppler and capillary growth in histological study compared with the control group at day 14 (p<0.05, respectively). In addition to promoting neovascularization, the MSCs with Epo significantly inhibited macrophage infiltration in perivascular are (p<0.05 vs. the control).
Conclusions: Epo induced the proliferative activity and enhanced the production of angiogenic cytokines in the cultured MSCs from bone marrow. In vivo study demonstrated that the short-term priming with Epo promoted the cellular engraftment and neovascularization in the MSC therapy for ischemic limb muscle. MSC implantation combined with Epo may be a novel and feasible strategy in therapeutic angiogeneis.
Author Disclosures: T. Mizukami: None. Y. Iso: None. H. Usui: None. C. Sato: None. M. Sasai: None. S. Shioda: None. H. Suzuki: None.
This research has received full or partial funding support from the American Heart Association
- © 2014 by American Heart Association, Inc.