1. Department of Neurological Surgery, University of California at San Francisco, San Francisco, California 94143-0520, USA
2. Howard Hughes Medical Institute, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109-0934, USA
3. Instituto Cavanilles, University of Valencia, Valencia 46100, Spain
4. Institute of Medical Microbiology, University of Dusseldorf, D-40225 Dusseldorf, Germany
5. Picower Center for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307, USA

Correspondence to: Arturo Alvarez-Buylla¹ Email: abuylla@itsa.ucsf.edu

Abstract

Recent studies have suggested that bone marrow cells possess a broad differentiation potential, being able to form new liver cells, cardiomyocytes and neurons^{1, 2}. Several groups have attributed this apparent plasticity to 'transdifferentiation'^{3, 4, 5}. Others, however, have suggested that cell fusion could explain these results^{6, 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.