Shock Wave Therapy Applied to Rat Bone Marrow-Derived Mononuclear Cells Enhances Formation of Cells Stained Positive for CD31 and Vascular Endothelial Growth Factor

Abstract

Background This study tested the hypothesis that shock wave (SW) therapy applied to bone marrow-derived mononuclear cells (BMDMNCs) enhances the formation of vascular endothelial growth factor (VEGF) and positively stained CD31 (CD31+) cells, an endothelial phenotype. Methods and ResultsThe BMDMNCs (~1.2×10 6 cells/2 femoral bones) were obtained from adult male Sprague-Dawley rats and SW therapy was applied once to BMDMNCs in group I (140 SW: defined as 140 shots in total, given at 0.09 mJ/mm 2 ), group II (280 SW), and group III (560 SW). Group IV was not treated by SW and served as the control group. Six experiments were done in each group. The BMDMNCs were cultured following SW therapy and the supernatants were collected on days 1, 3, 7 and 14 for assessment of VEGF levels. Immunocytochemical staining and flow cytometric measurement were performed on days 0 and 14. Experimental results demonstrated that VEGF levels were significantly higher in groups I-III than in group IV, and in group II than in group I at all intervals, and in group II than in group III on day 14 (all p values <0.005). Additionally, the number of positively stained VEGF cells on days 1, 3 and 14 and the number of newly formed CD31+ cells on day 14 were significantly higher in group II than in group IV (all p values <0.001). Conclusions These data suggest that application of SW to BMDMNCs significantly enhanced VEGF production and promoted differentiation of BMDMNCs into endothelial phenotype cells. (Circ J 2008; 72: 150 -156)

Autologous Bone Marrow-Derived Mononuclear Cell Therapy Prevents the Damage of Viable Myocardium and Improves Rat Heart Function Following Acute Anterior Myocardial Infarction

“…More importantly, our findings suggest that the new vessel formation is the result of angiogenesis and vasculogenesis and the effects of cytokines following BMDMNC transplantation. Interestingly, in vitro studies 32,33 have recently demonstrated that either cytokine or shock wave therapy applied to BMDMNC can enhance angiogenesis, expression of vascular endothelial growth factor, and positive CD31 cellular staining. Other recent investigations [5][6][7]34,35 have also shown that autologous bone marrow cell transplantation elicits angiogenesis, which in turn improves ischemia-induced organ dysfunction.…”

Double-Blind and Placebo-Controlled Study of the Effectiveness and Safety of Extracorporeal Cardiac Shock Wave Therapy for Severe Angina Pectoris

“…Thus, it remains to be examined whether our SW therapy promotes recruitment of bone marrow-derived cells by the ischemic myocardium of humans. 14, 15 Fourth, the detailed molecular mechanisms of the beneficial effects of SW in humans remain to be clarified in future studies. [3][4][5][6][7] In conclusion, the present double-blind, placebo-controlled study further confirmed the effectiveness and safety of our extracorporeal cardiac SW therapy for the treatment of severe angina pectoris, although large-scale multi-center study is needed.…”

Molecular mechanisms of the angiogenic effects of low-energy shock wave therapy: roles of mechanotransduction

“…Low-energy SW therapy has been reported to promote migration and differentiation of bone marrow-derived mononuclear cells (32,42), and the effects of the combination therapies of cell transplantation and SW have also been reported (2,5). Understanding of the detailed mechanisms of SW-induced angiogenesis may enable us to develop new therapeutic strategies (e.g., combination of pharmacotherapy and SW therapy).…”