Cytotherapy 13:431 (2011)
Bone marrow mesenchymal stromal cells with support of bispecifi cantibody and ultrasound-mediated microbubbles prevent myocardialfi brosis via the signal transducer and activators of transcription signaling pathway.
WEI DENG1 , QING-WEI CHEN1 , XING-SHENG LI1 , HAO LIU2 , SI-QIANG NIU2 ,YUE ZHOU2 , GUI-QIONG LI1 , DA-ZHI KE1 & XIAN-GANG MO1
1Gerontology Department of the No.2Hospital affi liated to Chongqing Medical University, Chongqing, China
Background aims. This study was initiated to investigate the effi cacy of myocardial fi brosis intervention via signal transducer and activators of transcription (STAT) signaling using bone marrow (BM) mesenchymal stromal cells (MSC) with the aid of bispecifi c antibody (BiAb) and ultrasound-mediated microbubbles (MB).
Methods . BiAb (anti-CD29*anti-myosin light chain antibody; AMLCA) was prepared and combined with isolated MSC from male mice and transfused into female mice with isoproterenol-induced myocardial fi brosis via the tail vein, followed by MB (MSC+ BiAb+MB). This study included seven groups: MSC+ BiAb+MB; MSC; BiAb; MB; MSC+BiAb; untreated; and control. Five weeks after treatment, expression levels of the sex-determining region of Y-chromosome (SRY), matrix metalloproteinases (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1 and vascular endothelial growth factor (VEGF) in myocardium were detected by fl uorescent quantitative real-time polymerase chain reaction (qRT-PCR). Collagen distribution was observed using Sirius Red staining. The protein expression of signal transducer and activators of transcription (STAT)1 and STAT3 was detected by Western blot.
Results . The highest homing number of MSC was in the MSC+ BiAb+MB group, second highest in the MSC+BiAb group, and lowest in MSC alone. Compared with the untreated group, MSC+BiAb+MB, MSC+BiAb and MSC groups had decreased levels of MMP-9, TIMP-1, STAT1 and collagen deposition, and increased levels of STAT3. Upregulated STAT3 and downregulated TIMP-1 were signifi cantly different in MSC+BiAb+MB compared with MSC alone or MSC+BiAb.
Conclusions. The homing rate and repairing effi cacy of MSC improved with treatment utilizing a combination of BiAb and MB. MSC can improve MMP – TIMP expression in injured myocardium and interfere with myocardial fi brosis after homing, a mechanism that may be related to the STAT-mediated signaling pathway.