| Objective: To isolate and purify marrow-derived mesenchymal stemcells (MSCs); to explore the effect of mesenchymal stem celltransplantation on cardiac function in rats with adriamycin (Adr)-inducedheart failure.Methods: To establish a rat model of heart failure, Adr was givenintraperitoneally to 12-week old F344 rats (n=36) weekly at a dose of 2mg?kg-1 body weight for 6 weeks. The surviving rats (n=32) were thenrandomly diveded into two groups, the cell tranplantation group (n=14)and the tranplantation control group (n=18). Another 10 normal rats servedas normal controls, which received saline injection instead of Adrinjection. MSCs were isolated from 8-week old F344 rats and cultured invitro. Cells at the third passage were identified with a flow cytometerand were labeled with (5-Bromo-2'-Dexuuridine, BrdU) beforetransplantation. One week after the last administration of Adr,BrdU-labeled MSCs (3×10~6 cells) or culture medium was transplanted intorats (the transplantation group and the transplantation control group,respectively) via femoral vein. Four weeks after the transplantation,cardiac function was evaluated with the use of a physiological recorder.Hearts were analyzed by immunohistochemical staining to identify thetransplanted BrdU-labeled cells.Rusults: Cultured MSCs at the third passage were positive for CD44and CD90 (99.8%±0.9% and 97.7%±0.4%, respectively), but negative forCD11b/c and CD34 (84.2%±0.2% and 97.91%±0.7%, respectively). Four weeksafter transplantation, BrdU-labeled transplanted MSCs could be found inthe hearts of the recipients. Hemodynamic measurements showed that Adrpressure (LVSP) , heart rate, maximal slope of left ventricular systolicpressure increment (LV +dP/dt) and diastolic pressure decrement (LV-dP/dt), as well as an increase in maximal left ventricular end-diastolicpressure (LVDP) in the transplantation control group(n=11)(86.34±6.53vs 128.23±14.82,347.17±24.30 vs 451.33±32.78,2292.07±106.04 vs3776.14±209.98,2226.30±138.93 vs 3264.85±256.22, 17.31±2.86 vs3.61±2.53,respectively, P<0.01, compared with the normal control group).Hemodynamic parameters such as LVSP, heart rate, LV +dP/dt and LV -dP/dtin the transplantation group(n=10) were significantly higher as comparedwith those in the transplantation control group(126.93±4.26 vs86.34±6.53 , 379.78±6.48 vs 347.17±24.30 , 2892.02±174.51 vs2292.07±106.04 , 2815.04±154.11 vs 2226.30±138.93 , respectively,P<0.01), but significantly lower as compared with those(except LVSP:126.93±4.26 vs 128.23±14.82,P>0.05) in the normal control group(379.78±6.48 vs 451.33±32.78,2892.02±174.51 vs 3776.14±2.9.98,2815.04±154.11 vs 3264.85±256.22,respectively, P<0.01). LVDP in thetransplantation group was significantly lower as compared with that inthe transplantation control group(11.02±2.74 vs 17.31±2.86,P<0.01),but significantly higher as compared with that in the normal control group(11.02±2.74 vs 3.61±2.53,P<0.01). Conclusions: 1. Cultured MSCs at the third passage express CD44 andCD90, but don't express CD11b/c and CD34. 2. A rat heart failure modelcan be successfully established by intraperitoneal injection of Adr. 3.Mesenchymal stem cell transplantation via femoral venous injection maysignificantly improve cardiac function in rats with Adr-induced heartfailure.
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