Korean J Gastroenterol.  2011 Sep;58(3):139-143. 10.4166/kjg.2011.58.3.139.

Clinical Trials with Stem Cells in Digestive Diseases and Future Perspectives

Affiliations
  • 1Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea. taeilkim@yuhs.ac

Abstract

Many techniques for isolation, expansion and handling of stem cells are being developed rapidly, and preclinical evidence has shown the possibility to use this technology for refractory diseases in the near future. Among refractory digestive diseases, Crohn's disease and liver cirrhosis may be two main diseases where stem cell therapy can be applied for anti-inflammation and regeneration of tissue. Currently, with respect to these two diseases, clinical trials using hematopoietic stem cells and mesenchymal stem cells from bone marrow or adipose tissue have shown some evidence of clinical benefits to immune modulation, suppression of inflammation and regeneration of functional cells. However, for the development of practical stem cell therapy, we need more data on underlying mechanisms, effective subpopulation of stem cells and its sources, and effective parameters for monitoring and estimation. With technical advances, the research on embryonic and induced pluripotent stem cells will also contribute to the new therapeutic strategies for digestive regenerative medicine. In the future, a variety of stem cell therapies may be therapeutic options for refractory digestive diseases, but many technical challenges remain to be solved.

Keyword

Stem cell; Clinical trial; Digestive system disease; Crohn's disease; Liver cirrhosis

MeSH Terms

Bone Marrow Cells/cytology
Clinical Trials as Topic
Crohn Disease/therapy
Digestive System Diseases/*therapy
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells/cytology
Humans
Liver Cirrhosis/therapy
Mesenchymal Stromal Cells/cytology/transplantation

Reference

References

1. Glocker EO, Kotlarz D, Boztug K, et al. Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N Engl J Med. 2009; 361:2033–2045.
Article
2. Gratwohl A, Passweg J, Bocelli-Tyndall C, et al. Autologous hematopoietic stem cell transplantation for autoimmune diseases. Bone Marrow Transplant. 2005; 35:869–879.
Article
3. van Bekkum DW. Experimental basis of hematopoietic stem cell transplantation for treatment of autoimmune diseases. J Leukoc Biol. 2002; 72:609–620.
4. Drakos PE, Nagler A, Or R. Case of Crohn's disease in bone marrow transplantation. Am J Hematol. 1993; 43:157–158.
Article
5. García-Bosch O, Ricart E, Panés J. Review article: stem cell therapies for inflammatory bowel disease – efficacy and safety. Aliment Pharmacol Ther. 2010; 32:939–952.
Article
6. Craig RM, Traynor A, Oyama Y, Burt RK. Hematopoietic stem cell transplantation for severe Crohn's disease. Bone Marrow Transplant. 2003; 32(Suppl 1):S57–S59.
Article
7. Oyama Y, Craig RM, Traynor AE, et al. Autologous hematopoietic stem cell transplantation in patients with refractory Crohn's disease. Gastroenterology. 2005; 128:552–563.
Article
8. Cassinotti A, Annaloro C, Ardizzone S, et al. Autologous haematopoietic stem cell transplantation without CD34+ cell selection in refractory Crohn's disease. Gut. 2008; 57:211–217.
Article
9. Uccelli A, Mancardi G, Chiesa S. Is there a role for mesenchymal stem cells in autoimmune diseases? Autoimmunity. 2008; 41:592–595.
Article
10. Fang B, Song YP, Liao LM, Han Q, Zhao RC. Treatment of severe therapy-resistant acute graft-versus-host disease with human adipose tissue-derived mesenchymal stem cells. Bone Marrow Transplant. 2006; 38:389–390.
Article
11. Le Blanc K, Frassoni F, Ball L, et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008; 371:1579–1586.
Article
12. Onken JE, Gallup D, Hanson J, et al. Successful outpatient treatment of refractory Crohn's disease using adult mesenchymal stem cells. ACG 2006 Final Program Book. 2006; 121.
13. Duijvestein M, Wildenberg ME, Vos AC, et al. S40 Phase I results of intravenous autologous bone marrow derived mesenchymal stromal cell treatment in refractory Crohn's disease. J Crohn's & Colitis Suppl. 2010; 4:34.
Article
14. Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001; 7:211–228.
Article
15. García-Olmo D, García-Arranz M, García LG, et al. Autologous stem cell transplantation for treatment of rectovaginal fistula in perianal Crohn's disease: a new cell-based therapy. Int J Colorectal Dis. 2003; 18:451–454.
16. García-Olmo D, García-Arranz M, Herreros D, Pascual I, Peiro C, Rodríguez-Montes JA. A phase I clinical trial of the treatment of Crohn's fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum. 2005; 48:1416–1423.
Article
17. Garcia-Olmo D, Herreros D, Pascual I, et al. Expanded adipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial. Dis Colon Rectum. 2009; 52:79–86.
18. Houlihan DD, Newsome PN. Critical review of clinical trials of bone marrow stem cells in liver disease. Gastroenterology. 2008; 135:438–450.
Article
19. Fürst G, Schulte am Esch J, Poll LW, et al. Portal vein embolization and autologous CD133+ bone marrow stem cells for liver regeneration: initial experience. Radiology. 2007; 243:171–179.
20. Terai S, Ishikawa T, Omori K, et al. Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy. Stem Cells. 2006; 24:2292–2298.
Article
21. Kim JK, Park YN, Kim JS, et al. Autologous bone marrow infusion activates the progenitor cell compartment in patients with advanced liver cirrhosis. Cell Transplant. 2010; 19:1237–1246.
Article
22. Kharaziha P, Hellström PM, Noorinayer B, et al. Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection: a phase I-II clinical trial. Eur J Gastroenterol Hepatol. 2009; 21:1199–1205.
Article
23. Couto BG, Goldenberg RC, da Fonseca LM, et al. Bone marrow mononuclear cell therapy for patients with cirrhosis: a Phase 1 study. Liver Int. 2011; 31:391–400.
Article
24. Salama H, Zekri AR, Bahnassy AA, et al. Autologous CD34+ and CD133+ stem cells transplantation in patients with end stage liver disease. World J Gastroenterol. 2010; 16:5297–5305.
25. Lyra AC, Soares MB, da Silva LF, et al. Infusion of autologous bone marrow mononuclear cells through hepatic artery results in a short-term improvement of liver function in patients with chronic liver disease: a pilot randomized controlled study. Eur J Gastroenterol Hepatol. 2010; 22:33–42.
Article
26. Rashid ST, Corbineau S, Hannan N, et al. Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. J Clin Invest. 2010; 120:3127–3136.
Article
27. Sullivan GJ, Hay DC, Park IH, et al. Generation of functional human hepatic endoderm from human induced pluripotent stem cells. Hepatology. 2010; 51:329–335.
Article
28. Jozefczuk J, Prigione A, Chavez L, Adjaye J. Comparative analysis of human embryonic stem cell and induced pluripotent stem cell-derived hepatocyte-like cells reveals current drawbacks and possible strategies for improved differentiation. Stem Cells Dev. 2011; 20:1259–1275.
Article
29. Inamura M, Kawabata K, Takayama K, et al. Efficient generation of hepatoblasts from human ES cells and iPS cells by transient overexpression of homeobox gene HEX. Mol Ther. 2011; 19:400–407.
Article
30. Spence JR, Mayhew CN, Rankin SA, et al. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature. 2011; 470:105–109.
Article
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