Molecular and Cellular Biochemistry

, Volume 387, Issue 1–2, pp 279–285 | Cite as

Impact of repeated intravenous bone marrow mesenchymal stem cells infusion on myocardial collagen network remodeling in a rat model of doxorubicin-induced dilated cardiomyopathy

  • Qin Yu
  • Qianxiao Li
  • Rongmei Na
  • Xiaofei Li
  • Baiting Liu
  • Lili Meng
  • Hanyu Liutong
  • Weiyi Fang
  • Ning Zhu
  • Xiaoqun Zheng
Article

Abstract

Bone marrow mesenchymal stem cells (MSCs) transplantation improved cardiac function and reduced myocardial fibrosis in both ischemic and non-ischemic cardiomyopathies. We evaluated the effects of repeated peripheral vein injection of MSCs on collagen network remodeling and myocardial TGF-β1, AT1, CYP11B2 (aldosterone synthase) gene expressions in a rat model of doxorubicin (DOX)-induced dilated cardiomyopathy (DCM). Thirty-eight out of 53 SD rats survived at 10 weeks post-DOX injection (2.5 mg/kg/week for 6 weeks, i.p.) were divided into DCM blank (without treatment, n = 12), DCM placebo (intravenous tail injection of 0.5 mL serum-free culture medium every other day for ten times, n = 13), and DCM plus MSCs group (intravenous tail injection of 5 × 106 MSCs dissolved in 0.5 mL serum-free culture medium every other day for 10 times, n = 13). Ten untreated rats served as normal controls. At 20 weeks after DOX injection, echocardiography, myocardial collagen content, myocardial expressions of types I and III collagen, TGF-β1, AT1, and CYP11B2 were compared among groups. At 20 weeks post-DOX injection, 8 rats (67 %) survived in DCM blank group, 9 rats (69 %) survived in DCM placebo group while 13 rats (100 %) survived in DCM plus MSCs group. Left ventricular end-diastolic diameter was significantly higher and ejection fraction was significantly lower in DCM blank and DCM placebo groups compared to normal control rats, which were significantly improved in DCM plus MSCs group (all p < 0.05 vs. DCM blank and DCM placebo groups). Moreover, myocardial collagen volume fraction, types I and III collagen, myocardial mRNA expressions of TGF-β1, AT1, CYP11B2, and collagen I/III ratio were all significantly lower in DCM plus MSCs group compared to DCM blank and DCM placebo groups (all p < 0.05). Repeated intravenous MSCs transplantation could improve cardiac function by attenuating myocardial collagen network remodeling possibly through downregulating renin–angiotensin–aldosterone system in DOX-induced DCM rats.

Keywords

Mesenchymal stem cells transplantation Dilated cardiomyopathy Collagen network remodeling Doxorubicin 

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Qin Yu
    • 1
  • Qianxiao Li
    • 1
    • 2
  • Rongmei Na
    • 1
  • Xiaofei Li
    • 1
    • 3
  • Baiting Liu
    • 1
  • Lili Meng
    • 1
  • Hanyu Liutong
    • 1
  • Weiyi Fang
    • 4
  • Ning Zhu
    • 5
  • Xiaoqun Zheng
    • 6
  1. 1.Department of CardiologyAffiliated Zhongshan Hospital of Dalian UniversityDalianChina
  2. 2.Department of CardiologyZhejiang Province Hospital of Integrated Traditional Chinese and Western MedicineHangzhouChina
  3. 3.Linqu County People’s Procuraforate of Shandong ProvinceWeifangChina
  4. 4.Department of CardiologyShanghai Chest HospitalShanghaiChina
  5. 5.Department of CardiologyThe Second Affiliated Hospital of Dalian Medical UniversityDalianChina
  6. 6.Department of CardiologyDalian Central HospitalDalianChina

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