Author + information
To explore the possibility of endogenous BMSC homing to myocardial infarcts which is induced by the ultrasound-targeted microbubble destruction (UTMD) mediated overexpression of SDF-1α, and the relationship between SDF-1α expression levels and BMSC homing activity.
We used UTMD to mediate transfection of adenovirus carrying SDF-1α genes in acute myocardial infarction (AMI) rats. AMI rat tail veins were injected with microbubbles carrying pAd-EGFP/SDF-1α mixtures, which were then ruptured by irradiation. All AMI rats were divided into control and experimental groups: myocardial infarction + ultrasound irradiation group (M + U/control group); and three experimental subgroups based on SDF-1α genes transfection length of time (S): 1 day, 2 days and 3 days of transfection (M + S1 + U, M + S2 + U and M + S3 + U). Blood SDF-1α concentration was then measured along with the number of BMSCs in the blood along with cardiomyocyte mRNA expression and protein content in the infarct area at 7 days after injection, which were CD73, CD90, CD105 and CXCR4 mRNA and protein.
SDF-1α concentrations in peripheral blood were significantly increased after transfection. ELISA analyses indicated that the SDF-1α concentration in the M + S3 + U group was 354.99 ± 31.38 pg/ml, which was 1.75 and 1.28 times that of the M + S1 + U and M + S2 + U groups, respectively; The number of BMSCs also significantly increased in peripheral blood and the infarcted area. Western blot analyses indicated that the expression of CD105 proteins in the M + S3 + U group was 4.90, 2.27 and 1.27 times that of the M + U, M + S1 + U and M + S2 + U groups, respectively. The differences were all statistically significant (P < 0.05). Further analyses indicated that the number of homing BMSCs increased with increased SDF-1α expression.
Our results suggest that UTMD-mediated transduction of exogenous SDF-1α genes into myocardial infarcted AMI rats can effectively promote the homing of endogenous BMSCs into the heart. Moreover, the number of homing stem cells was controlled by the level of SDF-1α expression.