Full Text:   <1833>

CLC number: R54

On-line Access: 

Received: 2009-05-25

Revision Accepted: 2009-07-03

Crosschecked: 2009-07-03

Cited: 25

Clicked: 3443

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
1. Reference List
Open peer comments

Journal of Zhejiang University SCIENCE B 2009 Vol.10 No.8 P.619~624

10.1631/jzus.B0920153


Protective paracrine effect of mesenchymal stem cells on cardiomyocytes


Author(s):  Mei-xiang XIANG, Ai-na HE, Jian-an WANG, Chun GUI

Affiliation(s):  Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China

Corresponding email(s):   wang_jian_an@tom.com

Key Words:  Mesenchymal stem cell (MSC), Apoptosis, Mitochondrial transmembrane potential, Hypoxia/reoxygenation (H/R)


Mei-xiang XIANG, Ai-na HE, Jian-an WANG, Chun GUI. Protective paracrine effect of mesenchymal stem cells on cardiomyocytes[J]. Journal of Zhejiang University Science B, 2009, 10(8): 619~624.

@article{title="Protective paracrine effect of mesenchymal stem cells on cardiomyocytes",
author="Mei-xiang XIANG, Ai-na HE, Jian-an WANG, Chun GUI",
journal="Journal of Zhejiang University Science B",
volume="10",
number="8",
pages="619~624",
year="2009",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B0920153"
}

%0 Journal Article
%T Protective paracrine effect of mesenchymal stem cells on cardiomyocytes
%A Mei-xiang XIANG
%A Ai-na HE
%A Jian-an WANG
%A Chun GUI
%J Journal of Zhejiang University SCIENCE B
%V 10
%N 8
%P 619~624
%@ 1673-1581
%D 2009
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B0920153

TY - JOUR
T1 - Protective paracrine effect of mesenchymal stem cells on cardiomyocytes
A1 - Mei-xiang XIANG
A1 - Ai-na HE
A1 - Jian-an WANG
A1 - Chun GUI
J0 - Journal of Zhejiang University Science B
VL - 10
IS - 8
SP - 619
EP - 624
%@ 1673-1581
Y1 - 2009
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B0920153


Abstract: 
Objective: The aim of this study was to test the protective effect of mesenchymal stem cells (MSCs) on cardiomyocytes in vitro and to investigate the anti-apoptotic signaling pathway. Methods: MSCs from Sprague-Dawley (SD) rats were separated and cultured. MSC medium was collected from MSCs cultured in serum-free Dulbecco’s modified eagle medium (DMEM) under hypoxia. Cultured cardiomyocytes from neonatal SD rats were exposed to hypoxia/reoxygenation (H/R) and treated with MSC medium. The apoptotic cardiomyocytes were stained with Annexin-V-fluorescein isothiocyanate (FITC), Hoechst 33342 and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). The mitochondrial transmembrane potential of cardiomyocytes was assessed using a fluorescence microscope. The expression of Bcl-2, Bax, cytochrome C, apoptosis-induced factor (AIF), and caspase-3 was tested by Western blot analysis. Results: Our data demonstrated that MSC medium reduced H/R-induced cardiomyocyte apoptosis, increased the Bcl-2/Bax ratio, and reduced the release of cytochrome C and AIF from mitochondria into the cytosol. Conclusion: MSCs protected the cardiomyocytes from H/R-induced apoptosis through a mitochondrial pathway in a paracrine manner.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1] Amado, L.C., Saliaris, A.P., Schuleri, K.H., John, M.S., Xie, J.S., Cattaneo, S., Durand, D.J., Fitton, T., Kuang, J.Q., Stewart, G., et al., 2005. Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc. Natl. Acad. Sci. USA, 102(32):11474-11479.

[2] Antonsson, B., 2001. Bax and other pro-apoptotic Bcl-2 family “killer-proteins” and their victim, the mitochondrion. Cell Tissue Res., 306(3):347-361.

[3] Chen, T.L., Wang, J.A., Shi, H., Gui, C., Luo, R.H., Xie, X.J., Xiang, M.X., Zhang, X., Cao, J., 2008. Cyclosporin a pre-incubation attenuates hypoxia/reoxygenation-induced apoptosis in mesenchymal stem cells. Scand. J. Clin. Lab. Invest., 68(7):585-593.

[4] Daugas, E., Susin, S.A., Zamzami, N., Ferri, K.F., Irinopoulou, T., Larochette, N., Prevost, M.C., Leber, B., Andrews, D., Penninger, J., Kroemer, G., 2000. Mitochondrio-nuclear translocation of aif in apoptosis and necrosis. Faseb. J., 14(5):729-739.

[5] Dobson, K.R., Reading, L., Haberey, M., Marine, X., Scutt, A., 1999. Centrifugal isolation of bone marrow from bone: an improved method for the recovery and quantitation of bone marrow osteoprogenitor cells from rat tibiae and femurae. Calcif. Tissue Int., 65(5):411-413.

[6] Fehlberg, S., Gregel, C.M., Göke, A., Göke, R., 2003. Bisphenol A diglycidyl ether-induced apoptosis involves Bax/Bid-dependent mitochondrial release of apoptosis-inducing factor (AIF), cytochrome C and Smac/DIABLO. Br. J. Pharmacol., 139(3):495-500.

[7] Gnecchi, M., He, H., Liang, O.D., Melo, L.G., Morello, F., Mu, H., Noiseux, N., Zhang, L., Pratt, R.E., Ingwall, J.S., Dzau, V.J., 2005. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat. Med., 11(4):367-368.

[8] Institute of Laboratory Animal Research, Commission on Life Science, National Research Council, 1996. Guide for the Care and Use of the Laboratory Animal. National Academic Press, Washington, DC, USA, p.1-140.

[9] Janssens, S., Dubois, C., Bogaert, J., Theunissen, K., Deroose, C., Desmet, W., Kalantzi, M., Herbots, L., Sinnaeve, P., Dens, J., et al., 2006. Autologous bone marrow-derived stem-cell transfer in patients with St-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet, 367(9505):113-121.

[10] Kemp, K.C., Hows, J., Donaldson, C., 2005. Bone marrow-derived mesenchymal stem cells. Leuk/Lymphoma, 46(11):1531-1544.

[11] Kinnaird, T., Stabile, E., Burnett, M.S., Shou, M., Lee, C.W., Barr, S., Fuchs, S., Epstein, S.E., 2004. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation, 109(12): 1543-1549.

[12] Kocher, A.A., Schuster, M.D., Szabolcs, M.J., Takuma, S., Burkhoff, D., Wang, J., Homma, S., Edwards, N.M., Itescu, S., 2001. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves. Cardiac. Function Nat. Med., 7(1): 430-436.

[13] Meyer, G.P., Wollert, K.C., Lotz, J., Steffens, J., Lippolt, P., Fichtner, S., Hecker, H., Schaefer, A., Arseniev, L., Hertenstein, B., Ganser, A., Drexler, H., 2006. Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months follow-up data from the randomized, controlled boost (bone marrow transfer to enhance St-elevation infarct regeneration) trial. Circulation, 113(10):1287-1294.

[14] Murphy, K.M., Streips, U.N., Lock, R.B., 1999. Bax membrane insertion during Fas(Cd95)-induced apoptosis precedes cytochrome C release and is inhibited by Bcl-2. Oncogene, 18(44):5991-5999.

[15] Shim, W.S., Jiang, S., Wong, P., Tan, J., Chua, Y.L., Tan, S., Sin, Y.K., Lim, T., Chua, C.H., Teh, M., et al., 2004. Ex vivo differentiation of human adult bone marrow stem cells into cardiomyocyte-like cells. Biochem. Biophys. Res. Commun., 324(2):481-488.

[16] Simpson, P., Savion, S., 1982. Differentiation of rat myocytes in single cell cultures with and without proliferating nonmyocardial cells. Cross-striations, ultrastructure, and chronotropic response to isoproterenol. Circ. Res., 50(1): 101-116.

[17] Susin, S.A., Lorenzo, H.K., Zamzami, N., Marzo, I., Snow, B.E., Brothers, G.M., Mangion, J., Jacotot, E., Costantini, P., Loeffler, M., et al., 1999. Molecular characterization of mitochondrial apoptosis-inducing factor. Nature, 397(6718):441-446.

[18] Takahashi, M., Li, T.S., Suzuki, R., Kobayashi, T., Ito, H., Ikeda, Y., Matsuzaki, M., Hamano, K., 2006. Cytokines produced by bone marrow cells can contribute to functional improvement of the infarcted heart by protecting cardiomyocytes from ischemic injury. Am. J. Physiol. Heart Circ. Physiol., 291(2):H886-H893.

[19] Tang, J., Xie, Q., Pan, G., Wang, J., Wang, M., 2006. Mesenchymal stem cells participate in angiogenesis and improve heart function in rat model of myocardial ischemia with reperfusion. Eur. J. Cardiothorac. Surg., 30(2): 353-361.

[20] Uemura, R., Xu, M., Ahmad, N., Ashraf, M., 2006. Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling. Circ. Res., 98(11):1414-1421.

[21] Wang, P.P., Wang, J.H., Yan, Z.P., Hu, M.Y., Lau, G.K., Fan, S.T., Luk, J.M., 2004. Expression of hepatocyte-like phenotypes in bone marrow stromal cells after HGF induction. Biochem. Biophys. Res. Commun., 320(3): 712-716.

[22] Xie, X.J., Wang, J.A., Cao, J., Zhang, X., 2006. Differentiation of bone marrow mesenchymal stem cells induced by myocardial medium under hypoxic conditions. Acta Pharmacol. Sin., 27(9):1153-1158.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - Journal of Zhejiang University-SCIENCE