Effects of transplantation timing on myocardial regeneration with bone marrow mesenchymal stem cells

    CAO Feng1,2, JIA Guoª²Liang2, NIU Liª²Li1, ZHANG Peng1, JIAO Wenª²Cang1, WANG Dongª²Mei1, LI Yanª²Hua1, PEI Xueª²Tao1

    Beijing Institute of Transfusion Medicine, Academy of Military Medical Sciences, Beijing 100850, China, 2Department of Cardiovasology, Xijing Hospital, Fourth Military Medical University, Xi¬ðan 710033, China

    ¡¾Abstract¡¿ AIM: To investigate the best time for rat mesenchymal stem cells (MSCs) engrafted in infarcted heart. METHODS: Myocardial infarctions (MI) were created by occluding the left anterior descending artery (LAD) in Wistar rats. The hearts were harvested and investigated by HE staining at different times after MI to study the inflammatory reaction. 2¡Á106 rMSCs (n=10/group, labeled with DAPI previously) at 1 h, 1 wk, 2 wk and 4 wk after MI or culture medium of the same volume (n=10) at 1 h after MI (as control) were injected into the marginal zone of the infarct region. Eight weeks after MI, morphologic, histologic and immunohistochemical characteristics and heart function were studied in different groups. RESULTS: After isolation and purification, rMSCs showed homogenous with CD44low+CD90high+/CD34-CD45-CD31-. No DAPI(+) MSCs survived when grafted 1 wk after MI with heart function and scar size similar to those in control. The cells transplanted at 1 h, 2 wk and 4 wk after MI were viable in large numbers in the host hearts and migrated from the margin to the center of the infarct region. Immunohistochemical staining revealed that the engrafted stem cells expressed both desmin and cTnI. The histologic and functional studies showed that the left ventricle functions and free wall scar areas in 1 h, 2 wk and 4 wk groups improved compared with those in both control and 1 wk groups(P<0.05). The transplantation of rMSCs at 2 wk after MI was associated with a significant increase of left ventricular endª²systolic pressure, the increase of ratio of left ventricular pressure rise and the limitation of scar area compared with those in the 1 h group and 4 wk group (P<0.05). CONCLUSION: Our findings suggest that excessive inflammatory reaction is not suitable for engrafted cells while subsequent growth factors, released within or around the injured myocardium, may have contributed to the graft survival and the functional recovery. ......