Combined Therapy with Extracorporeal Shockwave and Bone Marrow Derived Mesenchymal Stem Cell Alleviates Left Ventricular Dysfunction and Remodeling through Inhibiting Inflammatory Stimuli & Enhancing Angiogenesis in a Swine Acute Myocardial Infarction

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Jiunn-Jye Sheu (1), Hon-Kan Yip (2)

Institution:
(1) Dept. of Surgery, (2) Dept. of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan


Introduction:
We hypothesized that combined therapy with extracorporeal shock wave (ECSW) and bone marrow-derived mesenchymal stem cells (BMDMSCs) offered an additional benefit as compared with each treatment modality alone in alleviating left ventricular (LV) dysfunction through enhancing angiogenesis, exerting cytokine/paracrine effects, and suppressing inflammatory response/oxidative stress.

Methods:
Male mini-pigs, weighting 18-20 kg, were equally divided into group 1 (normal control), group 2 [AMI (by ligation of left anterior descending artery), group 3 (AMI- ECSW), group 4 (AMI-BMDMSC) and group 5 (AMI-ECSW- BMDMSC). The animals were sacrificed at day 60 after.

Results:
The baseline LV injection fraction (LVEF) did not differ among five groups (p>0.5). However, by day 60, the LVEF was highest in group 1 and lowest in group 2, higher in group 5 than in groups 3 and 4, and higher in group 3 than in group 4 (p<0.001), whereas the LV chamber size showed an opposite pattern of VLEF among the five groups (p<0.001). The cellular and protein levels of VEGF, CXCR4 and SDF-α in infarct area (IA) were progressively increased from groups 1 to 5 (all p<0.005). The small-vessel number and CD31 protein expression in IA were highest in groups 1 and 5, lowest in group 2, higher in group 4 than in group 3 (p<0.001). The protein (MMP-9, TNF-1α and NF-κB, oxidized protein) and cellular (CD14+, CD40+) biomarkers in IA were highest in group 2 and lowest group 1, lower in group 5 than in groups 3 and 4, and lower in group 4 than in group 3 (all p<0.001).

Discussion:
none

Conclusion:
Combined therapy is superior to either one alone for improving LVEF and inhibiting LV remodeling mainly through regulating angiogenesis and inflammation/oxidative stress.