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Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells

Nature Medicine volume 11, pages 367–368 (2005)Cite this article

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In conclusion, we provide evidence that, especially under hypoxic conditions, genetically modified bone marrow–derived mesenchymal stem cells overexpressing the Akt1 gene release paracrine factor(s) that exert cytoprotective effects on cardiomyocytes exposed to hypoxia. Notably, we show that myocardial protection can also be achieved in vivo by Akt concentrated medium injection after acute infarction. Thus, we propose that a substantial portion of the salutary effects of Akt-MSCs is attributable to protection of ischemic myocardium instead of de novo regeneration by cardiomyogenic differentiation of the donor cells. Taken together, our data support a 'paracrine hypothesis' of stem cell action in tissue protection and repair. These findings would suggest that the isolation of the secreted factor(s) may have important therapeutic application for the prevention of ischemic tissue damage.

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Figure 1: In vitro effects of conditioned medium.
Figure 2: In vivo effects of concentrated conditioned medium from MSCs exposed to hypoxia.

References

  1. Tomita, S. et al. Circulation 100 (19 Suppl), II247–56 (1999).

    CAS  PubMed  Google Scholar 

  2. Orlic, D. et al. Nature 410, 701–705 (2001).

    Article  CAS  Google Scholar 

  3. Jackson, K.A. et al. J. Clin. Invest. 107, 1395–1402 (2001).

    Article  CAS  Google Scholar 

  4. Toma, C., Pittenger, M.F., Cahill, K.S., Byrne, B.J. & Kessler, P.D. Circulation 105, 93–98 (2002).

    Article  Google Scholar 

  5. Nygren, J.M. et al. Nat. Med. 10, 494–501 (2004).

    Article  CAS  Google Scholar 

  6. Mangi, A.A. et al. Nat. Med. 9, 1195–1201 (2003).

    Article  CAS  Google Scholar 

  7. Gnecchi, M. et al. Circulation 110 (17 Suppl), III249 (2004).

    Google Scholar 

  8. Kajstura, J. et al. Lab. Invest. 74, 86–107 (1996).

    CAS  PubMed  Google Scholar 

  9. Friedrich, J., Apstein, C.S. & Ingwall, J.S. Circulation 92, 3527–3238 (1995).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by US National Institutes of Health Grants HL 72010, HL73219, HL 58516, HL 35610 (to V.J.D.) and HL 5320, HL 63985 (J.S.I). M. Gnecchi was partially supported by a research award from the University of Pavia and IRCCS Policlinico San Matteo, Pavia, Italy.

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  1. Luis G Melo

    Present address: Department of Physiology, Queen's University, Kingston, Ontario, K7L 3N6, Canada

Authors and Affiliations

  1. Department of Medicine, Duke University Medical Center, DUMC 3701, Durham, 27710, North Carolina, USA

    Massimiliano Gnecchi, Luis G Melo, Fulvio Morello, Hui Mu, Lunan Zhang, Richard E Pratt & Victor J Dzau

  2. Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, 02115, Massachusetts, USA

    Massimiliano Gnecchi, Huamei He, Olin D Liang, Luis G Melo, Fulvio Morello, Hui Mu, Nicolas Noiseux, Lunan Zhang, Richard E Pratt, Joanne S Ingwall & Victor J Dzau

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  1. Massimiliano Gnecchi
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Correspondence to Victor J Dzau.

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Gnecchi, M., He, H., Liang, O. et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med 11, 367–368 (2005). https://doi.org/10.1038/nm0405-367

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