Ultrasound-targeted Microbubble Destruction Enhances Delayed BMC Delivery and Attenuates Post-infarction Cardiac Remodeling by Inducing Engraftment Signals

Delayed administration of bone marrow cells (BMCs) at 2-4 weeks after successful reperfusion in patients with acute myocardial infarction does not improve cardiac function. The reduction in engraftment signals observed following this time interval might impair the effects of delayed BMC treatment. Here, we aimed to determine whether ultrasound-targeted microbubble destruction (UTMD) treatment could increase engraftment signals, enhance the delivery of delayed BMCs, and subsequently attenuate post-infarction cardiac remodeling. A myocardial ischemia/reperfusion (I/R) model was induced in Wistar rats via left coronary ligation for 45 min followed by reperfusion. Western blotting revealed that engraftment signals peaked at 7 days post-I/R and were dramatically lower at 14 days post-I/R. The lower engraftment signals at 14 days post-I/R could be triggered by UTMD treatment at a mechanical index of 1.0~1.9. The troponin I levels in the 1.9 mechanical index group were higher than in the other groups. Simultaneous hematoxylin and eosin staining and fluorescence revealed that the number of engrafted BMCs in the ischemic zone was greater in the group treated with than in the control groups ( P <0.05). Both UTMD and delayed BMC transplantation improved cardiac function and decreased cardiac fibrosis at 4 weeks after treatment, as compared with control groups (both P <0.05). Histopathology demonstrated increased capillary density, myocardial cell proliferation, and c-kit+ ce...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research