Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Cardiovascular Pharmacology

Differentiation of bone marrow mesenchymal stem cells induced by myocardial medium under hypoxic conditions

Abstract

Aim:

To explore whether bone marrow mesenchymal stem cells (MSC) can differentiate into myocardial-like cells induced by myocardial medium, especially the hypoxia/reoxygenation-conditioned medium of cardiomyocytes.

Methods:

Myocardial cells obtained from neonatal Sprague-Dawley rat ventricles were isolated and cultured in vitro and a hypoxia reoxygenation model was established. The MSC isolated from adult Sprague-Dawley rats were purified and then incubated with 3 different mediums: medium A - the conditioned medium of normal cardiomyocytes; medium B - the conditioned medium of cardiomyocytes after hypoxia reoxygenation; and the control medium - ordinary medium. The expressions of the cardiac myosin heavy chain (MHC), troponin T (TnT) and connexin 43 were investigated in the MSC after 24 h, 48 h and 72 h cultivation, respectively.

Results:

The MSC expressed MHC and TnT when incubated with the conditioned medium of cardiomyocytes after hypoxia reoxygenation, but did not express connexin 43. None of MHC, TnT and connexin 43 was detected in the MSC incubated with the conditioned medium of normal cardiomyocytes.

Conclusion:

The results indicate for the first time that myocardial medium for hypoxic preconditioning can induce MSC differentiation into myocardial-like cells.

References

  1. 1

    Shim WS, Jiang S, Wong P, Tan J, Chua YL, Tan YS, et al. Ex vivo differentiation of human adult bone marrow stem cells into cardiomyocyte-like cells. Biochem Biophys Res Commun 2004; 324: 481–8.

    CAS  Article  Google Scholar 

  2. 2

    Wang JS, Shum-Tim D, Galipeau J, Chedrawy E, Eliopoulos N, Chiu RC . Marrow stromal cells for cellular cardiomyoplasty: feasibility and potential clinical advantages. J Thorac Cardiovasc Surg 2000; 120: 999–1005.

    CAS  Article  Google Scholar 

  3. 3

    Han M, Trotta P, Coleman C, Linask KK . MCT-4, A511/Basigin and EF5 expression patterns during early chick cardiomyogenesis indicate cardiac cell differentiation occurs in a hypoxic environment. Dev Dyn 2006; 235: 124–31.

    CAS  Article  Google Scholar 

  4. 4

    Dobson KR, Reading L, Haberey M, Marine X, Scutt A . 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 1999; 65: 411–3.

    CAS  Article  Google Scholar 

  5. 5

    Makino S, Fukuda K, Miyoshi S, Konishi F, Kodama H, Pan J, et al. Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest 1999; 103: 697–705.

    CAS  Article  Google Scholar 

  6. 6

    Simpson PC, Savion S . Differentiation of rat myocytes in single cell culture with and without proliferating non myocardial myocytes: hypoxic cross striation, ultrastructure, and chronotropic response to catecholamines. Circ Res 1982; 50: 101–6.

    CAS  Article  Google Scholar 

  7. 7

    Negoro S, Kunisada K, Fujio Y, Funamoto M, Darville MI, Eizirik DL, et al. Activation of signal transducer and activator of transcription 3 protects cardiomyocytes from hypoxia/reoxygenation-induced oxidative stress through the upregulation of manganese superoxide dismutase. Circulation 2001; 104: 979–81.

    CAS  Article  Google Scholar 

  8. 8

    Xu FF, Liu XH, Cai LR . Role of hypoxia-inducible factor-1 alpha in the prevention of cardiomyocyte injury induced by hypoxic preconditioning. Acta Physiol Sin 2004, 56: 609–14.

    CAS  Google Scholar 

  9. 9

    Wakitani S, Saito T, Caplan AI . Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve 1995; 18: 1417–26.

    CAS  Article  Google Scholar 

  10. 10

    Fukuda K . Molecular characterization of regenerated cardiomyocytes derived from adult mesenchymal stem cells. Congenti Anom 2002; 42: 1–9.

    CAS  Article  Google Scholar 

  11. 11

    Yoon J, Min BG, Kim YH, Shim WJ, Ro YM, Lim DS . Differentiation, engraftment and functional effects of pre-treated mesenchymal stem cells in a rat myocardial infarct model. Acta Cardiol 2005; 60: 277–84.

    Article  Google Scholar 

  12. 12

    Xu M, Wani M, Dai YS, Wang J, Yan M, Ayub A, et al. Differentiation of bone marrow stromal cells into the cardiac phenotype requires intercellular communication with myocytes. Circulation 2004; 110: 2658–65.

    Article  Google Scholar 

  13. 13

    Yuan Y, Chen LF, Zhang SY, Wu W, Chen H, Yan XW . Differentiation of mesenchymal stem cells into cardiomyogenic cells under the induction of myocardial cell lysate. Zhonghua Xin Xue Guan Bing Za Zhi 2005; 33: 170–3.

    CAS  PubMed  Google Scholar 

  14. 14

    Rodriguez-Sinovas A, Garcia-Dorado D, Pina P, Ruiz-Meana M, Soler-Soler J . Effect of sarcolemmal rupture on myocardial electrical impedance during oxygen deprivation. Am J Physiol Heart Circ Physiol 2005; 288: H1396–403.

    CAS  Article  Google Scholar 

  15. 15

    Ito H, Adachi S, Tamamori M, Fujisaki H, Tanaka M, Lin M, et al. Mild hypoxia induces hypertrophy of cultured neonatal rat cardiomyocytes: a possible endogenous endothelin-1-mediated mechanism. J Mol Cell Cardiol 1996; 28: 1271–7.

    CAS  Article  Google Scholar 

  16. 16

    Shen JG, Quo XS, Jiang B, Li M, Xin W, Zhao BL . Chinonin, a novel drug against cardiomyocyte apoptosis induced by hypoxia and reoxygenation. Biochim Biophys Acta 2000; 1500: 217–26.

    CAS  Article  Google Scholar 

  17. 17

    Kacimi R, Long CS, Koudssi F, Karliner JS . Expression and regulation of adhesion molecules in cardiac cells by cytokines: Response to acute hypoxia. Circ Res 1998; 82: 576–86.

    CAS  Article  Google Scholar 

  18. 18

    Linask KK . Regulation of heart morphology: current molecular and cellular perspectives on the coordinated emergence of cardiac form and function. Birth Defects Res C Embryo Today 2003; 69: 14–24.

    CAS  Article  Google Scholar 

  19. 19

    Seko Y, Fujimura T, Taka H, Mineki R, Murayama K, Nagai R . Hypoxia followed by reoxygenation induces secretion of cyclophilin A from cultured rat cardiac myocytes. Biochem Biophys Res Commun 2004; 317: 162–8.

    CAS  Article  Google Scholar 

  20. 20

    Germack R, Dickenson JM . Adenosine triggers preconditioning through MEK/ERK1/2 signalling pathway during hypoxia/ reoxygenation in neonatal rat cardiomyocytes. J Mol Cell Cardiol 2005; 39: 429–42.

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Jian-an Wang.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Xie, Xj., Wang, Ja., Cao, J. et al. Differentiation of bone marrow mesenchymal stem cells induced by myocardial medium under hypoxic conditions. Acta Pharmacol Sin 27, 1153–1158 (2006). https://doi.org/10.1111/j.1745-7254.2006.00436.x

Download citation

Keywords

  • bone marrow
  • mesenchymal stem cells
  • cardiomyocyte
  • hypoxia
  • reoxygenation

Further reading

Search

Quick links