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

Alvarez-Dolado, Manuel and Pardal, Ricardo and Garcia-Verdugo, Jose M. and Fike, John R. and Lee, Hyun O. and Pfeffer, Klaus and Lois, Carlos and Morrison, Sean J. and Alvarez-Buylla, Arturo and Garcia-Verdugo, José-Manuel (2003) Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature, 425 (6961). pp. 968-973. ISSN 0028-0836. https://resolver.caltech.edu/CaltechAUTHORS:20181001-113520564

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Abstract

Recent studies have suggested that bone marrow cells possess a broad differentiation potential, being able to form new liver cells, cardiomyocytes and neurons. Several groups have attributed this apparent plasticity to ‘transdifferentiation’. Others, however, have suggested that cell fusion could explain these results. 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/nature02069DOIArticle
ORCID:
AuthorORCID
Alvarez-Dolado, Manuel0000-0002-0655-8289
Garcia-Verdugo, Jose M.0000-0001-9872-6499
Lois, Carlos0000-0002-7305-2317
Alvarez-Buylla, Arturo0000-0003-4426-8925
Garcia-Verdugo, José-Manuel0000-0001-9872-6499
Additional Information:© 2003 Springer Nature Limited. Received 18 August; accepted 24 September 2003; Published online 12 October 2003. 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. Animal care and bone marrow transplant: Animal care and all procedures were approved by the Institutional Animal Care Committees at UCSF and the University of Michigan. The authors declare that they have no competing financial interests.
Funders:
Funding AgencyGrant Number
NIHUNSPECIFIED
Sandler FoundationUNSPECIFIED
Ministerio de Ciencia Y Tecnologia (MCYT)UNSPECIFIED
Deutsche Forschungsgemeinschaft (DFG)UNSPECIFIED
Issue or Number:6961
Record Number:CaltechAUTHORS:20181001-113520564
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20181001-113520564
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:90063
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:02 Oct 2018 19:45
Last Modified:09 Mar 2020 13:18

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