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Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes

Nature volume 425, pages 968–973 (2003)Cite this article

Abstract

Recent studies have suggested that bone marrow cells possess a broad differentiation potential, being able to form new liver cells, cardiomyocytes and neurons1,2. Several groups have attributed this apparent plasticity to ‘transdifferentiation’3,4,5. Others, however, have suggested that cell fusion could explain these results6,7,8,9. Using a simple method based on Cre/lox recombination to detect cell fusion events, we demonstrate that bone-marrow-derived cells (BMDCs) fuse spontaneously with neural progenitors in vitro. Furthermore, bone marrow transplantation demonstrates that BMDCs fuse in vivo with hepatocytes in liver, Purkinje neurons in the brain and cardiac muscle in the heart, resulting in the formation of multinucleated cells. No evidence of transdifferentiation without fusion was observed in these tissues. These observations provide the first in vivo evidence for cell fusion of BMDCs with neurons and cardiomyocytes, raising the possibility that cell fusion may contribute to the development or maintenance of these key cell types.

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Figure 1: Method to detect cell fusion events.
Figure 2: Fusion of hepatocytes with BMDCs after bone marrow transplantation.
Figure 3: Purkinje cells fuse with BMDCs after bone marrow transplantation.
Figure 4: BMDCs fuse with cells in the heart.

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Acknowledgements

The authors thank G. Martin and P. Soriano for transgenic mouse lines, J. Maher at the UCSF Liver Centre for advice and assistance, and M. Kiel, O. Yilmaz and The University of Michigan Flow Cytometry Core for help with flow cytometry. R.P. thanks E. Schaller for technical help. M.A-D. thanks B. Rico, I. Cobos, T. Aragon and U. Borello for personal and scientific support. This work was supported by grants from NIH, the Sandler Foundation, the Spanish Ministry of Science and Technology (Ataxias Cerebelosa), and the Deutsche Forschungsgemeinschaft (DFG). R.P. was the recipient of a postdoctoral fellowship from the Spanish Ministry of Science and Technology.

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Authors and Affiliations

  1. Department of Neurological Surgery, University of California at San Francisco, San Francisco, California, 94143-0520, USA

    Manuel Alvarez-Dolado, John R. Fike & Arturo Alvarez-Buylla

  2. Howard Hughes Medical Institute, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, 48109-0934, USA

    Ricardo Pardal, Hyun O. Lee & Sean J. Morrison

  3. Instituto Cavanilles, University of Valencia, Valencia, 46100, Spain

    Jose M. Garcia-Verdugo

  4. Institute of Medical Microbiology, University of Dusseldorf, Dusseldorf, D-40225, Germany

    Klaus Pfeffer

  5. Picower Center for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139-4307, USA

    Carlos Lois

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  1. Manuel Alvarez-Dolado
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Correspondence to Arturo Alvarez-Buylla.

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Alvarez-Dolado, M., Pardal, R., Garcia-Verdugo, J. et al. Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature 425, 968–973 (2003). https://doi.org/10.1038/nature02069

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