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Damaged epithelia regenerated by bone marrow–derived cells in the human gastrointestinal tract


Studies have shown that bone marrow cells have the potential to differentiate into a variety of cell types. Here we show that bone marrow cells can repopulate the epithelia of the human gastrointestinal tract. Epithelial cells of male donor origin were distributed in every part of the gastrointestinal tract of female bone marrow transplant recipients. Donor-derived epithelial cells substantially repopulated the gastrointestinal tract during epithelial regeneration after graft-versus-host disease or ulcer formation. Regeneration of gastrointestinal epithelia with donor-derived cells in humans shows a potential clinical application of bone marrow–derived cells for repairing severely damaged epithelia, not only in the gastrointestinal tract but also in other tissues.

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Figure 1: Detection of donor-derived epithelial cells using Y-chromosome FISH (Y-FISH).
Figure 2: Donor-derived cells repopulated every part of the GI tract epithelia.
Figure 3: Donor-derived epithelial cells were increased in the GI tract during GVHD.
Figure 4: Donor-derived epithelial cells were increased in the GI tract during epithelial regeneration.


  1. Cheng, H. & Leblond, C.P. Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. I. Columnar cell. Am. J. Anat. 141, 461–474 (1974).

    Article  CAS  Google Scholar 

  2. Bach, S.P., Renehan, A.G. & Potten, C.S. Stem cells: the intestinal stem cell as a paradigm. Carcinogenesis 21, 469–476 (2000).

    Article  CAS  Google Scholar 

  3. Wright, N.A. in Stem Cells (ed. Potten, C.S.) 315–330 (Academic Press, London, UK, 1997).

    Book  Google Scholar 

  4. Booth, C. & Potten, C.S. Gut instincts: thoughts on intestinal epithelial stem cells. J. Clin. Invest. 105, 1493–1499 (2000).

    Article  CAS  Google Scholar 

  5. Negrin, R.S. & Blume, K.G. in Williams Hematology, edn. 13 (ed. Beutler, E.) 209–247 (McGraw-Hill, New York, New York, 2001).

    Google Scholar 

  6. Blau, H.M., Brazelton, T.R. & Weimann, J.M. The evolving concept of stem cell: entity or function? Cell 105, 829–841 (2001).

    Article  CAS  Google Scholar 

  7. Petersen, B.E. et al. Bone marrow as a potential source of hepatic oval cells. Science 284, 1168–1170 (1999).

    Article  CAS  Google Scholar 

  8. Lagasse, E. et al. Purified hematopoietic stem cell can differentiate into hepatocytes in vivo. Nature Med. 6, 1229–1234 (2000).

    Article  CAS  Google Scholar 

  9. Thiese, N.D. et al. Liver from bone marrow in humans. Hepatology 32, 11–16 (2000).

    Article  Google Scholar 

  10. Alison, M.R. et al. Hepatocytes from non-hepatic adult stem cells. Nature 406, 257 (2000).

    Article  CAS  Google Scholar 

  11. Orlic, D. et al. Bone marrow cells regenerate infarcted myocardium. Nature 410, 701–705 (2001).

    Article  CAS  Google Scholar 

  12. Jackson, K.A. et al. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J. Clin. Invest. 107, 1395–1402 (2001).

    Article  CAS  Google Scholar 

  13. Guissoni, E. et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 401, 390–394 (1999).

    Google Scholar 

  14. Brazelton, T.R., Rossi, F.M.V., Keshet, G.I. & Blau, H.M. From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290, 1775–1779 (2000).

    Article  CAS  Google Scholar 

  15. Krause, D.S. et al. Multi-organ, multi-lineage engraftment by a single bone marrow–derived stem cell. Cell 105, 369–377 (2001).

    Article  CAS  Google Scholar 

  16. Korbling, M. et al. Hepatocytes and epithelial cells of donor origin in recipients of peripheral blood stem cells. N. Engl. J. Med. 346, 738–746 (2002).

    Article  Google Scholar 

  17. Terada, N. et al. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 416, 542–545 (2002).

    Article  CAS  Google Scholar 

  18. Ying, Q-L. et al. Changing potency by spontaneous fusion. Nature 416, 545–548 (2002).

    Article  CAS  Google Scholar 

  19. Wumser, A.E. & Gage, F.H. Cell fusion causes confusion. Nature 416, 485–486 (2002).

    Article  Google Scholar 

  20. McKay, R. A more astonishing hypothesis. Nat. Biotech. 20, 426–427 (2002).

    Article  CAS  Google Scholar 

  21. Ishino, S. et al. Loss of material from chromosome arm 1p during malignant progression of meningioma revealed by fluorescent in situ hybridization. Cancer 83, 360–366 (1998).

    Article  CAS  Google Scholar 

  22. Nakahori, Y., Mitani, K., Yamada, M. & Nakagome, Y. A human Y-chromosome-specific repeated DNA family (DYZ1) consists of a tandem array of pentanucleotides. Nucleic Acids Res. 14, 7569–7580 (1986).

    Article  CAS  Google Scholar 

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This study was supported in part by grants-in-aid from the Japanese Ministry of Education, Culture, Sports, Science and Technology, the Japanese Ministry of Health, Labor and Welfare, Chiyoda Mutual Life Foundation, Japan Heath Sciences Foundation, and Creative Scientific Research by the Japan Society for the Promotion of Science. The authors would like to thank H. Okano and Y. Tanaka for helpful discussion, T. Mori for providing the clinical information, S. Kakinuma for technical assistance, Y. Iwao for providing the specimens and R. Fujisaki for manuscript preparation.

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Correspondence to Mamoru Watanabe.

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Okamoto, R., Yajima, T., Yamazaki, M. et al. Damaged epithelia regenerated by bone marrow–derived cells in the human gastrointestinal tract. Nat Med 8, 1011–1017 (2002).

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