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Autologous bone marrow cell infusion therapy for liver cirrhosis patients

  • Topics
  • Regenerative medicine in Hepato-Biliary-Pancreatic Sciences
  • Published:
Journal of Hepato-Biliary-Pancreatic Sciences

Abstract

We developed a novel cell therapy, autologous bone marrow cell infusion (ABMi) therapy, using autologous bone marrow, for liver cirrhosis patients. Our study depends on the findings from basic studies that bone marrow cell infusion repairs liver fibrosis in the cirrhotic liver, and improves liver function and the survival rate. Beginning in November 2003, we started a clinical study and found that ABMi therapy was safe and effective for liver cirrhosis patients. Multicenter trials in Japan and Korea have also shown the effectiveness of ABMi therapy. In this review, we report the current status of ABMi therapy for liver cirrhosis patients.

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Abbreviations

CCl4:

Carbon tetrachloride

GFP:

Green fluorescent protein

BMI:

Bone marrow cell infusion

ABMi:

Autologous bone marrow cell infusion

MMP:

Matrix metalloproteinase

LC:

Liver cirrhosis

MNC:

Mononuclear cell

FACS:

Fluorescent-activated cell sorter

LR cell:

Liver repair cell

References

  1. Terai S, Ishikawa T, Omori K, Aoyama K, Marumoto Y, Urata Y, Yokoyama Y, Uchida K, Yamasaki T, Fujii Y, Okita K, Sakaida I. Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy. Stem Cells. 2006;24:2292–8.

    Article  CAS  PubMed  Google Scholar 

  2. Terai S, Marumoto Y, Ishikawa T, Aoyama K, Omori K, Yamamoto N, Sakaida I, Nishina H, Okumoto K, Saitou T, Kawata S, Okita K. LRCT Study: ABMI therapy for LC patient. Saiseiiryou Gakkai. 2006;5:79–87.

    Google Scholar 

  3. Alison MR, Poulsom R, Jeffery R, Dhillon AP, Quaglia A, Jacob J, Novelli M, Prentice G, Williamson J, Wright NA. Hepatocytes from non-hepatic adult stem cells. Nature. 2000;406:257.

    Article  CAS  PubMed  Google Scholar 

  4. Theise ND, Nimmakayalu M, Gardner R, Illei PB, Morgan G, Teperman L, Henegariu O, Krause DS. Liver from bone marrow in humans. Hepatology. 2000;32:11–6.

    Article  CAS  PubMed  Google Scholar 

  5. Terai S, Yamamoto N, Omori K, Sakaida I, Okita K. A new cell therapy using bone marrow cells to repair damaged liver. J Gastroenterol. 2002;37(Suppl 14):162–3.

    CAS  PubMed  Google Scholar 

  6. Terai S, Sakaida I, Yamamoto N, Omori K, Watanabe T, Ohata S, Katada T, Miyamoto K, Shinoda K, Nishina H, Okita K. An in vivo model for monitoring trans-differentiation of bone marrow cells into functional hepatocytes. J Biochem (Tokyo). 2003;134:551–8.

    CAS  Google Scholar 

  7. Sakaida I, Terai S, Yamamoto N, Aoyama K, Ishikawa T, Nishina H, Okita K. Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice. Hepatology. 2004;40:1304–11.

    Article  PubMed  Google Scholar 

  8. Terai S, Sakaida I, Nishina H, Okita K. Lesson from the GFP/CCl4 model-translational research project: the development of cell therapy using autologous bone marrow cells in patients with liver cirrhosis. J Hepatobiliary Pancreat Surg. 2005;12:203–7.

    Article  PubMed  Google Scholar 

  9. Ishikawa T, Terai S, Urata Y, Marumoto Y, Aoyama K, Sakaida I, Murata T, Nishina H, Shinoda K, Uchimura S, Hamamoto Y, Okita K. Fibroblast growth factor 2 facilitates the differentiation of transplanted bone marrow cells into hepatocytes. Cell Tissue Res. 2006;323:221–31.

    Article  CAS  PubMed  Google Scholar 

  10. Ishikawa T, Terai S, Urata Y, Marumoto Y, Aoyama K, Murata T, Mizunaga Y, Yamamoto N, Nishina H, Shinoda K, Sakaida I. Administration of fibroblast growth factor 2 in combination with bone marrow transplantation synergistically improves carbon-tetrachloride-induced liver fibrosis in mice. Cell Tissue Res. 2007;327:463–70.

    Article  CAS  PubMed  Google Scholar 

  11. Yamamoto N, Terai S, Ohata S, Watanabe T, Omori K, Shinoda K, Miyamoto K, Katada T, Sakaida I, Nishina H, Okita K. A subpopulation of bone marrow cells depleted by a novel antibody, anti-Liv8, is useful for cell therapy to repair damaged liver. Biochem Biophys Res Commun. 2004;313:1110–8.

    Article  CAS  PubMed  Google Scholar 

  12. Ohata S, Nawa M, Kasama T, Yamasaki T, Sawanobori K, Hata S, Nakamura T, Asaoka Y, Watanabe T, Okamoto H, Hara T, Terai S, Sakaida I, Katada T, Nishina H. Hematopoiesis-dependent expression of CD44 in murine hepatic progenitor cells. Biochem Biophys Res Commun. 2009;379:817–23.

    Article  CAS  PubMed  Google Scholar 

  13. Watanabe T, Nakagawa K, Ohata S, Kitagawa D, Nishitai G, Seo J, Tanemura S, Shimizu N, Kishimoto H, Wada T, Aoki J, Arai H, Iwatsubo T, Mochita M, Satake M, Ito Y, Matsuyama T, Mak TW, Penninger JM, Nishina H, Katada T. SEK1/MKK4-mediated SAPK/JNK signaling participates in embryonic hepatoblast proliferation via a pathway different from NF-kappaB-induced anti-apoptosis. Dev Biol. 2002;250:332–47.

    CAS  PubMed  Google Scholar 

  14. Higashiyama R, Inagaki Y, Hong YY, Kushida M, Nakao S, Niioka M, Watanabe T, Okano H, Matsuzaki Y, Shiota G, Okazaki I. Bone marrow-derived cells express matrix metalloproteinases and contribute to regression of liver fibrosis in mice. Hepatology. 2007;45:213–22.

    Article  CAS  PubMed  Google Scholar 

  15. Oyagi S, Hirose M, Kojima M, Okuyama M, Kawase M, Nakamura T, Ohgushi H, Yagi K. Therapeutic effect of transplanting HGF-treated bone marrow mesenchymal cells into CCl4-injured rats. J Hepatol. 2006;44:742–8.

    Article  CAS  PubMed  Google Scholar 

  16. Lyra AC, Soares MB, da Silva LF, Fortes MF, Silva AG, Mota AC, Oliveira SA, Braga EL, de Carvalho WA, Genser B, dos Santos RR, Lyra LG. Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease. World J Gastroenterol. 2007;13:1067–73.

    CAS  PubMed  Google Scholar 

  17. Mohamadnejad M, Alimoghaddam K, Mohyeddin-Bonab M, Bagheri M, Bashtar M, Ghanaati H, Baharvand H, Ghavamzadeh A, Malekzadeh R. Phase 1 trial of autologous bone marrow mesenchymal stem cell transplantation in patients with decompensated liver cirrhosis. Arch Iran Med. 2007;10:459–66.

    CAS  PubMed  Google Scholar 

  18. Mohamadnejad M, Namiri M, Bagheri M, Hashemi SM, Ghanaati H, Zare Mehrjardi N, Kazemi Ashtiani S, Malekzadeh R, Baharvand H. Phase 1 human trial of autologous bone marrow-hematopoietic stem cell transplantation in patients with decompensated cirrhosis. World J Gastroenterol. 2007;13:3359–63.

    CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science and the Japan Society of Technology and Grants-in-Aid for Translational Research from the Ministry of Health, Labor and Welfare and the Knowledge Cluster Initiative.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1, Ube, Yamaguchi, 755-8505, Japan

    Shuji Terai & Isao Sakaida

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  1. Shuji Terai
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  2. Isao Sakaida
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Correspondence to Shuji Terai.

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Terai, S., Sakaida, I. Autologous bone marrow cell infusion therapy for liver cirrhosis patients. J Hepatobiliary Pancreat Sci 18, 23–25 (2011). https://doi.org/10.1007/s00534-010-0305-1

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  • DOI: https://doi.org/10.1007/s00534-010-0305-1

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