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Present Status and Perspectives of Stem Cell-Based Therapies for Gastrointestinal Diseases

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Abstract

In recent years the interest in stem cell-based therapies for gastrointestinal injury has been increasing continuously. From the clinical point of view, transplantation of bone marrow derived stem cells may represent an alternative therapy for gastrointestinal injury, such as radioactive injury, inflammatory bowel disease, and other refractory gastrointestinal tract injury. There were several reports indicated that bone marrow derived stem cells located in the injured gastrointestinal tract and contributed to its regeneration by differentiating into functional epithelia cells or infusing with the gastrointestinal stem cells. Although the concept of cell-based therapy for various diseases of the gastrointestinal is widely accepted, the practical approach in humans remains difficult. Here we discussed the recent published data on clinical and experimental bone marrow stem cell transplantation and the possible role of stem cells in gastrointestinal tissue repair.

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References

  1. Ayala, A., Song, G. Y., Chung, C. S., Redmond, K. M., & Chaudry, I. H. (2000). Immune depression in polymicrobial sepsis: The role of necrotic (injured) tissue and endotoxin. Critical Care Medicine, 28, 2949–2955. doi:10.1097/00003246-200008000-00044.

    Article  PubMed  CAS  Google Scholar 

  2. Nussler, N. C., Muller, A. R., Weidenbach, H., Vergopoulos, A., Platz, K. P., Volk, H. D., et al. (2003). IL-10 increases tissue injury after selective intestinal ischemia/reperfusion. Annals of Surgery, 238, 49–58. doi:10.1097/00000658-200307000-00007.

    Article  PubMed  Google Scholar 

  3. Ford, H. R. (2006). Mechanism of nitric oxide-mediated intestinal barrier failure: Insight into the pathogenesis of necrotizing enterocolitis. Journal of Pediatric Surgery, 41, 294–299. doi:10.1016/j.jpedsurg.2005.11.003.

    Article  PubMed  Google Scholar 

  4. Neal, M. D., Leaphart, C., Levy, R., Prince, J., Billiar, T. R., Watkins, S., et al. (2006). Enterocyte TLR4 mediates phagocytosis and translocation of bacteria across the intestinal barrier. Journal of Immunology, 176, 3070–3079.

    CAS  Google Scholar 

  5. Cetin, S., Leaphart, C. L., Li, J., Ischenko, I., Hayman, M., Upperman, J., et al. (2006). Nitric oxide inhibits enterocyte migration through activation of RhoA-GTPase in a SHP-2-dependent manner. American Journal of Physiology: Gastrointestinal and Liver Physiology, 292, G1347–G1358. doi:10.1152/ajpgi.00375.2006.

    Article  CAS  Google Scholar 

  6. Khalil, P. N., Weiler, V., Nelson, P. J., Khalil, M. N., Moosmann, S., Mutschler, W. E., et al. (2007). Nonmyeloablative stem cell therapy enhances microcirculation and tissue regeneration in murine inflammatory bowel disease. Gastroenterology, 132, 944–954. doi:10.1053/j.gastro.2006.12.029.

    Article  PubMed  Google Scholar 

  7. Haider, H., & Ashraf, M. (2005). Bone marrow cell transplantation in clinical perspective. Journal of Molecular and Cellular Cardiology, 38, 225–235. doi:10.1016/j.yjmcc.2004.12.005.

    Article  PubMed  CAS  Google Scholar 

  8. Nagy, R. D., Tsai, B. M., Wang, M., Markel, T. A., Brown, J. W., & Meldrum, D. R. (2005). Stem cell transplantation as a therapeutic approach to organ failure. Journal of Surgical Research, 129, 152–160. doi:10.1016/j.jss.2005.04.016.

    Article  PubMed  CAS  Google Scholar 

  9. Krause, D. S., Theise, N. D., Collector, M. I., Henegariu, O., Hwang, S., Gardner, R., et al. (2001). Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell, 105, 369–377. doi:10.1016/S0092-8674(01)00328-2.

    Article  PubMed  CAS  Google Scholar 

  10. Lagasse, E., Connors, H., & Al-Dhalimy, M. (2000). Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nature Medicine, 6, 1229–1234. doi:10.1038/81326.

    Article  PubMed  CAS  Google Scholar 

  11. Bengala, C., Guarneri, V., & Giovannetti, E. (2005). Prolonged fixed dose rate infusion of gemcitabine with autologous haemopoietic support in advanced pancreatic adenocarcinoma. British Journal of Cancer, 93, 35–40. doi:10.1038/sj.bjc.6602673.

    Article  PubMed  CAS  Google Scholar 

  12. Brazelton, T. R., Rossi, F. M., & Keshet, G. I. (2000). From marrow to brain: Expression of neuronal phenotypes in adult mice. Science, 290, 1775–1779. doi:10.1126/science.290.5497.1775.

    Article  PubMed  CAS  Google Scholar 

  13. Goodell, M. A., Jackson, K. A., Majka, S. M., Mi, T., Wang, H., Pocius, J., et al. (2001). Stem cell plasticity in muscle and bone marrow. Annals of the New York Academy of Sciences, 938, 208–218.

    Article  PubMed  CAS  Google Scholar 

  14. Jackson, K. A., Majka, S. M., Wang, H., Pocius, J., Hartley, C. J., Majesky, M. W., et al. (2001). Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. Journal of Clinical Investigation, 107, 1395–1402. doi:10.1172/JCI12150.

    Article  PubMed  CAS  Google Scholar 

  15. Orlic, D., Kajstura, J., & Chimenti, S. (2001). Bone marrow cells regenerate infracted myocardium. Nature, 410, 701–705. doi:10.1038/35070587.

    Article  PubMed  CAS  Google Scholar 

  16. Okamoto, R., Yajima, T., Yamazaki, M., Kanai, T., Mukai, M., Okamoto, S., et al. (2002). Damaged epithelial regenerated by bone marrow derived cells in the human gastrointestinal tract. Nature Medicine, 8, 1011–1017. doi:10.1038/nm755.

    Article  PubMed  CAS  Google Scholar 

  17. Kayahara, T., Sawada, M., Takaishi, S., Fukui, H., Seno, H., Fukuzawa, H., et al. (2003). Candidate markers for stem and early progenitor cells, Musashi-1 and Hes1, are expressed in crypt base columnar cells of mouse small intestine. FEBS Letters, 535, 131–135. doi:10.1016/S0014-5793(02)03896-6.

    Article  PubMed  CAS  Google Scholar 

  18. Booth, C., & Potten, C. S. (2000). Gut instincts: Thoughts on intestinal epithelial stem cells. Journal of Clinical Investigation, 105, 1493–1499. doi:10.1172/JCI10229.

    Article  PubMed  CAS  Google Scholar 

  19. Markel, T. A., Crisostomo, P. R., Lahm, T., Novotny, N. M., Rescorla, F. J., Tector, J., et al. (2008). Stem cells as a potential future treatment of pediatric intestinal disorders. Journal of Pediatric Surgery, 43, 1953–1963. doi:10.1016/j.jpedsurg.2008.06.019.

    Article  PubMed  Google Scholar 

  20. Dekaney, C. M., Rodriguez, J. M., Graul, M. C., & Henning, S. J. (2005). Isolation and characterization of a putative intestinal stem cell fraction from mouse jejunum. Gastroenterology, 129, 1567–1580. doi:10.1053/j.gastro.2005.08.011.

    Article  PubMed  CAS  Google Scholar 

  21. Barker, N., Ridgway, R. A., van Es, J. H., van de Wetering, M., Begthel, H., & van den Born, M. (2009). Crypt stem cells as the cells-of-origin of intestinal cancer. Nature, 457, 608–611. doi:10.1038/nature07602.

    Article  PubMed  CAS  Google Scholar 

  22. Yen, T. H., & Wright, N. A. (2006). The gastrointestinal tract stem cell niche. Stem Cell Rev, 2, 203–212. doi:10.1007/s12015-006-0048-1.

    Article  PubMed  CAS  Google Scholar 

  23. Brittan, M., & Wright, N. A. (2004). Stem cell in gastrointestinal structure and neoplastic development. Gut, 53, 899–910. doi:10.1136/gut.2003.025478.

    Article  PubMed  CAS  Google Scholar 

  24. Brittan, M., Hunt, T., Jeffery, R., Poulsom, R., Forbes, S. J., Hodivala-Dilke, K., et al. (2002). Bone marrow derivation of pericryptal myofibroblasts in the mouse and human small intestine and colon. Gut, 50, 752–757. doi:10.1136/gut.50.6.752.

    Article  PubMed  CAS  Google Scholar 

  25. Okamoto, R., & Watanabe, M. (2003). Prospects for regeneration of gastrointestinal epithelia using bone marrow cells. Trends in Molecular Medicine, 9, 286–290. doi:10.1016/S1471-4914(03)00110-2.

    Article  PubMed  Google Scholar 

  26. Resbeut, M., Marteau, P., Cowen, D., Richaud, P., Bourdin, S., Dubois, J. B., et al. (1997). A randomized double blind placebo controlled multicenter study of mesalazine for the prevention of acute radiation enteritis. Radiotherapy and Oncology, 44, 59–63. doi:10.1016/S0167-8140(97)00064-9.

    Article  PubMed  CAS  Google Scholar 

  27. Chen, S. W., Liang, J. A., Yang, S. N., Hung, Y. C., Yeh, L. S., Shiau, A. C., et al. (2004). Radiation injury to intestine following hysterectomy and adjuvant radiotherapy for cervical cancer. Gynecologic Oncology, 95, 208–214. doi:10.1016/j.ygyno.2004.07.003.

    Article  PubMed  Google Scholar 

  28. Carr, K. E., Hume, S. P., Nelson, A. C., O’Shea, O., Hazzard, R. A., & McCullough, J. S. (1996). Morphological profiles of neutron and X-irradiated small intestine. Journal of Radiation Research (Tokyo), 37, 38–48. doi:10.1269/jrr.37.38.

    Article  CAS  Google Scholar 

  29. Crook, J., Esche, B., & Futter, N. (1996). Effect of pelvic radiotherapy for prostate cancer on bowel, bladder, and sexual function: The patient’s perspective. Urology, 47, 387–394. doi:10.1016/S0090-4295(99)80458-0.

    Article  PubMed  CAS  Google Scholar 

  30. Zhang, J., Gong, J. F., Zhang, W., Zhu, W. M., & Li, J. S. (2008). Effects of transplanted bone marrow mesenchymal stem cells on the irradiated intestine of mice. Journal of Biomedical Science, 15, 585–594. doi:10.1007/s11373-008-9256-9.

    Article  PubMed  CAS  Google Scholar 

  31. Jiang, Y., Jahagirdar, B. N., Reinhardt, R. L., Schwartz, R. E., Keene, C. D., Ortiz-Gonzalez, X. R., et al. (2002). Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 418, 41–49. doi:10.1038/nature00870.

    Article  PubMed  CAS  Google Scholar 

  32. Devine, S. M., Cobbs, C., Jennings, M., Bartholomew, A., & Hoffman, R. (2003). Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates. Blood, 101, 2999–3001. doi:10.1182/blood-2002-06-1830.

    Article  PubMed  CAS  Google Scholar 

  33. Semont, A., Francois, S., Mouiseddine, M., Francois, A., Sache, A., Frick, J., et al. (2007). Mesenchymal stem cells increase self-renewal of small intestinal epithelium and accelerate structural recovery after radiation injury. Advances in Experimental Medicine and Biology, 585, 19–30. doi:10.1007/978-0-387-34133-0_2.

    Article  Google Scholar 

  34. Okamoto, R., Matsumoto, T., & Watanabe, M. (2006). Regeneration of the intestinal epithelial: Regulation of bone marrow-derived epithelial cell differentiation towards secretory lineage cells. Human Cell, 19, 71–75. doi:10.1111/j.1749-0774.2006.00010.x.

    Article  PubMed  Google Scholar 

  35. Sands, B. E. (2007). Infammatory bowel disease: Past, present, and future. Journal of Gastroenterology, 42, 16–25. doi:10.1007/s00535-006-1995-7.

    Article  PubMed  Google Scholar 

  36. Kashyap, A., & Forman, S. J. (1998). Autologous bone marrow transplantation for non-Hodgkin’s lymphoma resulting in long term remission of coincidental Crohn’s disease. British Journal of Haematology, 103, 651–652. doi:10.1046/j.1365-2141.1998.01059.x.

    Article  PubMed  CAS  Google Scholar 

  37. Lopez-Cubero, S. O., Sullivan, K. M., & McDonald, G. B. (1998). Course of Crohn’s disease after allogeneic marrow transplantation. Gastroenterology, 114, 433–440. doi:10.1016/S0016-5085(98)70525-6.

    Article  PubMed  CAS  Google Scholar 

  38. Ditschkowski, M., Einsele, H., Schwerdtfeger, R., Bunjes, D., Trenschel, R., Beelen, D. W., et al. (2003). Improvement of inflammatory bowel disease after allogeneic stem-cell transplantation. Transplantation, 75, 1745–1747. doi:10.1097/01.TP.0000062540.29757.E9.

    Article  PubMed  Google Scholar 

  39. Oyama, Y., Craig, R. M., Traynor, A. E., Quigley, K., Statkute, L., Halverson, A., et al. (2005). Autologous hematopoietic stem cell transplantation in patients with refractory Crohn’s disease. Gastroenterology, 128, 552–563. doi:10.1053/j.gastro.2004.11.051.

    Article  PubMed  Google Scholar 

  40. Cassinotti, A., Annaloro, C., Ardizzone, S., Onida, F., Della Volpe, A., Clerici, M., et al. (2008). Autologous haematopoietic stem cell transplantation without CD34 + cell selection in refractory Crohn’s disease. Gut, 57, 211–217. doi:10.1136/gut.2007.128694.

    Article  PubMed  CAS  Google Scholar 

  41. Mitsuyama, K., Andoh, A., Masuda, J., Yamasaki, H., Kuwaki, K., Takedatsu, H., et al. (2008). Mobilization of bone marrow cells by leukocytapheresis in patients with ulcerative colitis. Ther Apher Dial, 12, 271–277. doi:10.1111/j.1744-9987.2008.00587.x.

    Article  PubMed  Google Scholar 

  42. Padron Velazquez, J. L. (2006). Stem cell fusion as an ultimate line of defense against xenobiotics. Medical Hypotheses, 67, 383–387. doi:10.1016/j.mehy.2006.01.031.

    Article  PubMed  CAS  Google Scholar 

  43. Ambrosi, D. J., & Rasmussen, T. P. (2005). Reprogramming mediated by stem cell fusion. Journal of Cellular and Molecular Medicine, 9, 320–330. doi:10.1111/j.1582-4934.2005.tb00358.x.

    Article  PubMed  CAS  Google Scholar 

  44. Rizvi, A. Z., Swain, J. R., Davies, P. S., Bailey, A. S., Decker, A. D., Willenbring, H., et al. (2006). Bone marrow-derived cells fuse with normal and transformed intestinal stem cells. Proceedings of the National Academy of Sciences of the United States of America, 103, 6321–6325. doi:10.1073/pnas.0508593103.

    Article  PubMed  CAS  Google Scholar 

  45. Matsumoto, T., Okamoto, R., Yajima, T., Mori, T., Okamoto, S., Ikeda, Y., et al. (2005). Increase of bone marrow-derived secretory lineage epithelial cells during regeneration in the human intestine. Gastroenterology, 128, 1851–1867. doi:10.1053/j.gastro.2005.03.085.

    Article  PubMed  CAS  Google Scholar 

  46. Fishbein, T., Novitskiy, G., Mishra, L., Matsumoto, C., Kaufman, S., Goyal, S., et al. (2007). NOD2-expressing bone marrow-derived cells appear to regulate epithelial innate immunity of the transplanted human small intestine. Gut, 57, 323–330. doi:10.1136/gut.2007.133322.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Benyan Wu.

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Li Yan and Changhao Cai are co-first author

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Yan, L., Cai, C., Li, J. et al. Present Status and Perspectives of Stem Cell-Based Therapies for Gastrointestinal Diseases. Stem Cell Rev and Rep 5, 278–282 (2009). https://doi.org/10.1007/s12015-009-9070-4

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