PMID- 16915405 OWN - NLM STAT- MEDLINE DCOM- 20070423 LR - 20181201 IS - 0031-6768 (Print) IS - 0031-6768 (Linking) VI - 453 IP - 1 DP - 2006 Oct TI - Homing and differentiation of mesenchymal stem cells delivered intravenously to ischemic myocardium in vivo: a time-series study. PG - 43-52 AB - Mesenchymal stem cells (MSCs) are potential sources of cells for tissue repair. However, little information is available about the time course of homing and differentiation of systemically delivered MSCs after acute myocardial ischemia (MI). In the present study, MSCs were isolated from male rat bone marrow and expanded in vitro. Female rats were divided randomly into three groups. Three hours after coronary ligation, the transplanted group received an infusion of MSCs through the tail vein; at the same time, a coronary-ligated control group was injected with culture medium, and a normal (unligated) group received MSCs. Homing of MSCs to the heart was assessed by expression of the Y chromosome sry gene using fluorescence in situ hybridization (FISH) at 3 days, 1, 4, and 8 weeks after transplantation. Immunofluorescent staining was used to examine markers for cardiomyocytes, endothelial cells, and smooth muscle cells. Hemodynamics in the hearts was also measured to assess cardiac function. At each time point, sry-positive cells were present in the cardiac tissue in transplanted group but not in the hearts of normal and control group animals. The number of sry-positive cells was significantly higher at 1 week compared to 3 days after transplantation. No significant difference was found in the number of sry-positive cells among those of 1, 4, and 8 weeks after transplantation. At 3 days and 1 week after transplantation, the sry-positive cells in the transplanted group lacked troponin, desmin, smooth muscle alpha-actin, and CD31. At the later time points, cardiomyocytes, smooth muscle cells, and endothelial cells bearing sry were identified in the transplanted group. The cardiac function in transplanted group showed higher improvement at 4 and 8 weeks compared to 1 week after transplantation. Our data suggest that intravenously delivered MSCs are capable of homing toward the ischemic myocardium, and the fastigium of homing appeared around 1 week after MI. The differentiation of MSCs to cardiomyocytes, smooth muscle cells, and endothelial cells shows to be time dependent and arises at 1 to 4 weeks after transplantation. FAU - Jiang, Wenhui AU - Jiang W AD - Medical College, Xi'an Jiaotong University, No. 1 Jiankang Road, Xi'an, Shaanxi 710061, China. FAU - Ma, Aiqun AU - Ma A FAU - Wang, Tingzhong AU - Wang T FAU - Han, Ke AU - Han K FAU - Liu, Yu AU - Liu Y FAU - Zhang, Yanmin AU - Zhang Y FAU - Dong, Anping AU - Dong A FAU - Du, Yuan AU - Du Y FAU - Huang, Xin AU - Huang X FAU - Wang, Jun AU - Wang J FAU - Lei, Xinjun AU - Lei X FAU - Zheng, Xiaopu AU - Zheng X LA - eng PT - Journal Article DEP - 20060817 PL - Germany TA - Pflugers Arch JT - Pflugers Archiv : European journal of physiology JID - 0154720 SB - IM MH - Animals MH - Cell Differentiation/physiology MH - Female MH - Heart/*physiology MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/cytology/*physiology MH - Myocardial Ischemia/pathology/*therapy MH - Rats MH - Rats, Sprague-Dawley MH - Regeneration/*physiology MH - Time Factors EDAT- 2006/08/18 09:00 MHDA- 2007/04/24 09:00 CRDT- 2006/08/18 09:00 PHST- 2006/04/27 00:00 [received] PHST- 2006/06/08 00:00 [accepted] PHST- 2006/05/29 00:00 [revised] PHST- 2006/08/18 09:00 [pubmed] PHST- 2007/04/24 09:00 [medline] PHST- 2006/08/18 09:00 [entrez] AID - 10.1007/s00424-006-0117-y [doi] PST - ppublish SO - Pflugers Arch. 2006 Oct;453(1):43-52. doi: 10.1007/s00424-006-0117-y. Epub 2006 Aug 17.