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Stem Cell Reviews and Reports

, Volume 8, Issue 3, pp 972–981 | Cite as

Phase II Trial: Undifferentiated Versus Differentiated Autologous Mesenchymal Stem Cells Transplantation in Egyptian Patients with HCV Induced Liver Cirrhosis

  • Mervat El-Ansary
  • Iman Abdel-Aziz
  • Sherif Mogawer
  • Samah Abdel-Hamid
  • Olfat Hammam
  • Salwa Teaema
  • Marwa Wahdan
Article

Abstract

The study was aimed to evaluate the effect of autologous transplantation of BM-derived undifferentiated and differentiated MSCs in cirrhotic patients following chronic hepatitis C virus infection. Twenty-five patients with Child C liver cirrhosis, MELD score >12 were included. They were divided into 2 groups. Group I, the MSCs group (n = 15), this group was subdivided into two subgroups: Ia & Ib (undifferentiated and differentiated respectively). Group II (control group; n = 10) involved patients with cirrhotic liver under conventional supportive treatment. Ninety ml BM was aspirated from the iliac bone for separation of MSCs. Surface expression of CD271, CD29 and CD34 were analyzed using flowcytometry. Hepatogenesis was assessed by immunohistochemical expression of OV6, AFP and albumin. Finally approximately 1 million MSCs/Kg were suspended in saline and were placed in blood bag and injected slowly intravenously over 15 min at a rate of 5 drops/min in one session. Follow up of patients at 3 and 6 months postinfusion revealed partial improvement of liver function tests with elevation of prothrombin concentration and serum albumin levels, decline of elevated bilirubin and MELD score in MSCs group. Statistical comparisons between the two subgroups (group Ia & Ib) did not merit any significant difference regarding clinical and laboratory findings. In conclusion: Bone marrow MSCs transplantation either undifferentiated or differentiated can be used as a potential treatment for liver cirrhosis.

Keywords

MSCs Transplantation Liver cirrhosis Differentiation 

Abbreviations

BM

Bone marrow

MSCs

Mesenchymal stem cells

MELD score

Model of End–Stage Liver Disease

HSCs

Hematopoietic stem cells

HSC

Hepatic stellate cells

Notes

Acknowledgment

The authors would like to thank Kasr El-Aini hospital for in part supporting of this study. We also thank El-Ansary private laboratories, our patients for their willing participation in our research.

Disclosure

The authors of this manuscript have no conflicts of interest to disclose.

References

  1. 1.
    Christoforou, N., & Gearhart, J. D. (2007). Stem cells and their potential in cell-based cardiac therapies. Progress in Cardiovascular Diseases, 49, 396–413.PubMedCrossRefGoogle Scholar
  2. 2.
    Chop, M., & Li, Y. (2002). Treatment of neural injury with marrow stromal cells. Lancet Neurology, 1, 92–100.CrossRefGoogle Scholar
  3. 3.
    Pittenger, M. F. (2008). Mesenchymal stem cells from adult bone marrow. Methods in Molecular Biology, 449, 27–44.PubMedGoogle Scholar
  4. 4.
    Satija, N. K., Singh, V. K., Verma, Y. K., et al. (2009). Mesenchymal stem cell-based therapy: a new paradigm in regenerative medicine. Journal of Cellular and Molecular Medicine, 13(11–12), 4385–4402.PubMedCrossRefGoogle Scholar
  5. 5.
    Silva, W. A., Covas, D. T., Panepucci, R. A., et al. (2003). The profile of gene expression of human marrow mesenchymal stem cells. Stem Cells, 21, 661–669.PubMedCrossRefGoogle Scholar
  6. 6.
    Bühring, H. J., Battula, V. L., Treml, S., et al. (2007). Novel markers for the prospective isolation of human MSC. Annals of the New York Academy of Sciences, 1106, 262–271.PubMedCrossRefGoogle Scholar
  7. 7.
    Gronthos, S., Zannettino, A. C., Hay, D. J., et al. (2003). Molecular and cellular characterization of highly purified stromal stems derived from human bone marrow. Journal of Cell Science, 116, 1827–1835.PubMedCrossRefGoogle Scholar
  8. 8.
    Boiret, N., Rapatel, C., Veyrat-Masson, R., et al. (2005). Characterization of nonexpanded mesenchymal progenitor cells from normal adult human bone marrow. Experimental Hematology, 33, 219–225.PubMedCrossRefGoogle Scholar
  9. 9.
    Baddoo, M., Hill, K., Wilkinson, R., et al. (2003). Characterization of mesenchymal stem cells isolated from murine bone marrow by negative selection. Journal of Cellular Biochemistry, 89, 1235–1249.PubMedCrossRefGoogle Scholar
  10. 10.
    Fang, B., Shi, M., Liao, L., et al. (2004). Systemic infusion of FLK1 mesenchymal stem cells ameliorates carbontetrachloride-induced liver fibrosis in mice. Transplantation, 78, 83–88.PubMedCrossRefGoogle Scholar
  11. 11.
    Freeman, R. B., Steffick, D. E., Guidinger, M. K., et al. (2008). Liver and intestine transplantation in the United States, 1977–2006. American Journal of Transplantation, 8, 958–976.PubMedCrossRefGoogle Scholar
  12. 12.
    Parekkadan, B., Poll, D. V., Suganuma, K., et al. (2007). Mesenchymal stem cell-derived molecules reverse fulmimant hepatic failure. PLoS One, 2(9), 941–949.CrossRefGoogle Scholar
  13. 13.
    Dai, L., Li, H. Y., Guan, L., et al. (2008). The therapeutic potential of bone marrow-derived mesenchymal stem cells on hepatic cirrhosis. Stem Cell Research, 2, 16–25.PubMedCrossRefGoogle Scholar
  14. 14.
    Libbrecht, L., Desmet, V., Van Damme, B., et al. (2000). The immunohistochemical phenotype of dysplastic foci in human liver: correlation with putative progenitor cells. Journal of Hepatology, 33, 76–84.PubMedCrossRefGoogle Scholar
  15. 15.
    Xiao, J. C., Ruck, P., Adam, A., et al. (2003). Small epithelial cells in human liver cirrhosis exhibit features of hepatic stem like cells: immunohistochemical, electron microscopic and immunoelectron microscopic findings. Histopathology, 42, 141–149.PubMedCrossRefGoogle Scholar
  16. 16.
    Svegliati-Baroni, G., De Minicis, S., & Marzioni, M. (2008). Hepatic fibrogenesis in response to chronic liver injury: novel insights on the role of cell-to-cell interaction and transition. Liver International, 28(8), 1052–1064.PubMedCrossRefGoogle Scholar
  17. 17.
    Darwish, M. A., Faris, R., Darwish, N., et al. (2001). Hepatitis C and cirrhotic liver disease in the Nile delta of Egypt: a community-based study. The American Journal of Tropical Medicine and Hygiene, 64, 147–153.PubMedGoogle Scholar
  18. 18.
    Li, J., Li, M., Niu, B., et al. (2011). Therapeutic potential of stem cell in liver regeneration. Frontiers of Medicine, 5(1), 26–32.PubMedCrossRefGoogle Scholar
  19. 19.
    Kale, S. (2003). Bone marrow stem cells contribute to repair of the ischemically injured renal tubule. The Journal of Clinical Investigation, 112, 42–49.PubMedGoogle Scholar
  20. 20.
    Thiese, N. D. (2006). Emergent themes of liver stem cell biology: niche, quiescence, self-renewal, and plasticity. American Journal of Physiology—Gastrointestinal and Liver Physiology, 290, 189–193.CrossRefGoogle Scholar
  21. 21.
    Sarah, S., Tamora, V., Peggy, P., et al. (2006). Sequential exposure to cytokines reflecting embryogenesis: the key for in vitro differentiation of adult bone marrow stem cells into functional hepatocyte-like cells. Toxicological Sciences, 94(2), 330–341.CrossRefGoogle Scholar
  22. 22.
    Lange, C., Bassler, P., Lioznov, M. V., et al. (2005). Hepatocytic gene expression in cultured rat mesenchymal stem cells. Transplantation Proceedings, 37, 276–279.PubMedCrossRefGoogle Scholar
  23. 23.
    Terai, S., Ishikawa, T., Omori, K., et al. (2006). Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy. Stem Cells, 24, 2292–2298.PubMedCrossRefGoogle Scholar
  24. 24.
    Mohamadnejad, M., Alimoghaddam, K., Mohyeddin-Bonab, M., et al. (2007). Phase 1 trial of autologous bone marrow mesenchymal stem cell transplantation in patients with decompensated liver cirrhosis. 10(4), 459–466.Google Scholar
  25. 25.
    Abdel Aziz, M. T., Atta, H., Mahfouz, S., et al. (2007). Therapeutic potential of bone marrow-derived mesenchymal stem cells on experimental liver fibrosis. Clinical Biochemistry, 40, 893–899.PubMedCrossRefGoogle Scholar
  26. 26.
    Zhao, D. C., Lei, J. X., Chen, R., et al. (2005). Bone marrow-derived mesenchymal stem cells protect against experimental liver fibrosis in rat. World Journal of Gastroenterology, 14, 3431–3440.Google Scholar
  27. 27.
    Aquino, J. B., Bolontrade, M. F., Garcia, M. G., et al. (2010). Mesencymal stem cells as therapeutic tools and gene carrirers in hepatocellular carcinoma and liver fibrosis. Gene Therapy, 17, 62–708.CrossRefGoogle Scholar
  28. 28.
    Chen, X., Li, Y., Wang, L., et al. (2002). Ischemic rat brain extracts induce human marrow stromal cell growth factor production. Neuropathology, 22, 275–279.PubMedCrossRefGoogle Scholar
  29. 29.
    Zhang, B., Inagaki, M., Jiang, B., et al. (2009). Effects of BM and hepatocyte transplantation on liver injury. Journal of Surgical Research, 157(1), 71–80.PubMedCrossRefGoogle Scholar
  30. 30.
    Oyagi, S., Hirose, M., Kojima, M., et al. (2006). Therapeutic effect of transplanting HGF-treated bone marrowmesenchymal cells into CCl4-injured rats. Journal of Hepatology, 44, 742–748.PubMedCrossRefGoogle Scholar
  31. 31.
    Yu, Y., Lu, L., Qian, X., et al. (2010). Antifibrotic effect of hepatocyte growth factor-expressing mesenchymal stem cells in small-for-size liver transplant rats. Stem Cells and Development, 19(6), 903–914.PubMedCrossRefGoogle Scholar
  32. 32.
    Fox, I. J., & Strom, S. C. (2008). To be or not to be: generation of hepatocytes from cells outside the liver. Gastroenterology, 134, 878–881.PubMedCrossRefGoogle Scholar
  33. 33.
    Di Bonzo, L. V., Ferrero, I., Cravanzola, C., et al. (2008). Human mesenchymal stem cells as a two-edged sword in hepatic regenerative medicine: engraftment and hepatocyte differentiation versus profibrogenic potential. Gut, 57, 223–231.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Mervat El-Ansary
    • 1
  • Iman Abdel-Aziz
    • 2
  • Sherif Mogawer
    • 3
  • Samah Abdel-Hamid
    • 1
  • Olfat Hammam
    • 4
  • Salwa Teaema
    • 2
  • Marwa Wahdan
    • 2
  1. 1.Department of Clinical Pathology, Kasr El-AiniCairo UniversityCairoEgypt
  2. 2.Department of HaematologyTheodor Bilharz Research InstituteGizaEgypt
  3. 3.Department of Hepatology and Gastroenterology, Kasr El-AiniCairo UniversityCairoEgypt
  4. 4.Department of PathologyTheodor Bilharz Research InstituteGizaEgypt

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