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BIOLOGICAL SCIENCES / MEDICAL SCIENCES
Bone marrow-derived cells fuse with normal and transformed intestinal stem cells

Adnan Z. Rizvi^*, John R. Swain, Paige S. Davies, Alexis S. Bailey, Adria D. Decker, Holger Willenbring, Markus Grompe^,¶, William H. Fleming^,¶, and Melissa H. Wong^,¶,||,**

*Departments of Surgery, Dermatology, **Cell and Developmental Biology, and Molecular and Medical Genetics, Center for Hematologic Malignancies, Division of Hematology and Medical Oncology, and ^¶Oregon Cancer Institute, Oregon Stem Cell Center, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239

Edited by Suzanne Cory, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia, and approved March 3, 2006 (received for review October 5, 2005)

Transplanted adult bone marrow-derived cells (BMDCs) have been shown to adopt the phenotype and function of several nonhematopoietic cell lineages and promote tumorigenesis. Beyond its cancer enhancing potential, cell fusion has recently emerged as an explanation of how BMDCs regenerate diseased heptocytes, contribute to Purkinje neurons and skeletal and cardiac muscle cells, and participate in skin and heart regeneration. Although bone marrow-derived epithelial cells also have been observed in the intestine, fusion as a mechanism has not been investigated. Here, we show that transplanted BMDCs fuse with both normal and neoplastic intestinal epithelium. Long-term repopulation by donor-derived cells was detected in all principal intestinal epithelial lineages including enterocytes, goblet cells, Paneth cells, and enteroendocrine cells, suggesting that the fusion partners of the BMDCs are long-lived intestinal progenitors or stem cells. Fusion of BMDCs with neoplastic epithelium did not result in tumor initiation. Our findings suggest an unexpected role for BMDCs in both regeneration and tumorigenesis of the intestine.

intestine | tumorigenesis | cell fusion | tissue regeneration

Author contributions: A.Z.R., W.H.F., and M.H.W. designed research; A.Z.R., J.R.S., P.S.D., A.S.B., A.D.D., and M.H.W. performed research; J.R.S., H.W., M.G., W.H.F., and M.H.W. contributed new reagents/analytic tools; J.R.S., P.S.D., A.S.B., M.G., W.H.F., and M.H.W. analyzed data; and A.Z.R., P.S.D., H.W., and M.H.W. wrote the paper.

Conflict of interest statement: No conflicts declared.

This paper was submitted directly (Track II) to the PNAS office.

^||To whom correspondence should be addressed. E-mail: wongme{at}ohsu.edu

© 2006 by The National Academy of Sciences of the USA

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