Journal of Gastrointestinal Cancer

, Volume 42, Issue 1, pp 11–19 | Cite as

Simultaneous Injection of Autologous Mononuclear Cells with TACE in HCC Patients; Preliminary Study

  • Alaa Ismail
  • Ahmed AlDorry
  • Mohammed Shaker
  • Reda Elwekeel
  • Khaled Mokbel
  • Doaa Zakaria
  • Anas Meshaal
  • Firas Zahr ElDeen
  • Abdulhafez Selim
Original Article

Abstract

Background

The discovery of the pluripotent stem cells made the prospect of cell therapy and tissue regeneration a clinical reality, especially with the evidence of contribution of the stem cells of bone marrow origin in hepatic regeneration. Infusion of bone marrow stem cells before trans-arterial chemoembolization may help to increase liver volume and consequently increase hepatic reserve in patients with HCC, and this may improve the outcome of this procedure.

Materials and Methods

Four Child B class patients with unresectable hepatocellular carcinoma treated by transarterial chemoembolization were injected with autologous bone marrow mononuclear layer containing stem cell in the hepatic artery feeding the contralateral lobe of the liver in the same session, follow-up of the patients was done by doing liver profile and CT liver volumetry before the surgery and 3 months later.

Results

We observed that patients receiving stem cell therapy simultaneously with TACE had shown a significant improvement in biological and volumetric parameters of liver function compared to those historically reported of patients receiving TACE only who usually shows deterioration of liver parameters.

Conclusion

BMC infusion into the hepatic artery synchronized with TACE for patients with chronic liver disease complicated with HCC is safe, feasible, and demonstrated an improvement in both biological and radiological volumetric parameters.

Keywords

Chemoembolization Stem cell therapy HCC Autologous bone marrow stem cells 

References

  1. 1.
    Cha C, DeMatteo RP, Blumgart LH. Surgery and ablative therapy for hepatocellular carcinoma. J Clin Gastroenterol. 2002;35(5 Suppl 2):S130–7.PubMedGoogle Scholar
  2. 2.
    Jemel A et al. Cancer statistics. CA Cancer J Clin. 2006;56(2):106–30.Google Scholar
  3. 3.
    Alsowmely AM, Hodgson HJ. Non-surgical treatment of hepatocellular carcinoma. Aliment Pharmacol Ther. 2002;16:1–15.PubMedGoogle Scholar
  4. 4.
    Chen MS, Li JQ, Zhang YQ, Lu LX, Zhang WZ, Yuan YF, et al. High-dose iodized oil transcatheter arterial chemoembolization for patients with large hepatocellular carcinoma. World J Gastroenterol. 2002;8:74–8.PubMedGoogle Scholar
  5. 5.
    Li L, Wu PH, Li JQ, Zhang WZ, Lin HG, Zhang YQ. Segmental transcatheter arterial embolization for primary hepatocellular carcinoma. World J Gastroenterol. 1998;4:511–12.PubMedGoogle Scholar
  6. 6.
    Huo TI, Huang YH, Wu JC, Lee PC, Chang FY, Lee SD. Survival benefit of cirrhotic patients with hepatocellular carcinoma treated by percutaneous ethanol injection as a salvage therapy. Scand J Gastroenterol. 2002;37:350–5.PubMedGoogle Scholar
  7. 7.
    Teratani T, Ishikawa T, Shiratori Y, Shiina S, Yoshida H, Imamura M, et al. Hepatocellular carcinoma in elderly patients: beneficial therapeutic efficacy using percutaneous ethanol injection therapy. Cancer. 2002;95:816–23.PubMedGoogle Scholar
  8. 8.
    Jiang HC, Liu LX, Piao DX, Xu J, Zheng M, Zhu AL, et al. Clinical short-term results of radiofrequency ablation in liver cancers. World J Gastroenterol. 2002;8:624–30.PubMedGoogle Scholar
  9. 9.
    Allgaier HP, Galandi D, Zuber I, Blum HE. Radiofrequency thermal ablation of hepatocellular carcinoma. Dig Dis. 2001;19:301–10.PubMedGoogle Scholar
  10. 10.
    Vogl TJ, Mack MG, Roggan A, Straub R, Eichler KC, Muller PK, et al. Internally cooled power laser for MR-guided interstitial laser-induced thermotherapy of liver lesions: initial clinical results. Radiology. 1998;209:381–5.PubMedGoogle Scholar
  11. 11.
    Pacella CM, Bizzarri G, Cecconi P, Caspani B, Magnolfi F, Bianchini A, et al. Hepatocellular carcinoma: long-term results of combined treatment with laser thermal ablation and transcatheter arterial chemoembolization. Radiology. 2001;219:669–78.PubMedGoogle Scholar
  12. 12.
    Itamoto T, Katayama K, Fukuda S, Fukuda T, Yano M, Nakahara H, et al. Percutaneous microwave coagulation therapy for primary or recurrent hepatocellular carcinoma: long-term results. Hepatogastroenterology. 2001;48:1401–5.PubMedGoogle Scholar
  13. 13.
    Seki T, Tamai T, Nakagawa T, Imamura M, Nishimura A, Yamashiki N, et al. Combination therapy with transcatheter arterial chemoembolization and percutaneous microwave coagulation therapy for hepatocellular carcinoma. Cancer. 2000;89:1245–51.PubMedGoogle Scholar
  14. 14.
    Dominguez J, Rafecas A, Torras J, Fabregat J, Guardiola J, Jaurrieta Qian J, et al. Combined interventional therapies of HCC. A prognostic index of the survival of patients with unresectable hepatocellular carcinoma after transcatheter arterial chemoembolization. Cancer. 2000;88:50–7.PubMedGoogle Scholar
  15. 15.
    Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359:1734–9.PubMedGoogle Scholar
  16. 16.
    Vogl TJ, Trapp M, Schroeder H, Mack M, Schuster A, Schmitt J, et al. Transarterial chemoembolization for hepatocellular carcinoma: volumetric and morphologic CT criteria for assessment of prognosis and therapeutic success—results from a liver transplantation center. Radiology. 2000;214:349–57.PubMedGoogle Scholar
  17. 17.
    Bartolozzi C, Lencioni R, Caramella D, Vignali C, Cioni R, Mazzeo S, et al. Treatment of large HCC: transcatheter arterial chemoembolization combined with percutaneous ethanol injection versus repeated transcatheter arterial chemoembolization. Radiology. 1995;197:812–18.PubMedGoogle Scholar
  18. 18.
    Janis and Friends, Hepatitis C Support web site, Liver Cancer 2008.Google Scholar
  19. 19.
    Biselli M, Andreone P, Gramenzi A, Trevisani F, Cursaro C, Rossi C, et al. Transcatheter arterial chemoembolization therapy for patients with hepatocellular carcinoma: a case controlled study. Clin Gastroenterol Hepatol. 2005;3(9):918–25.PubMedGoogle Scholar
  20. 20.
    National Institutes of Health. Clinical trials. Transcatheter arterial chemoembolization. http://www.clinicaltrials.gov/. Accessed 17 December 2007.
  21. 21.
    National Comprehensive Cancer Network. Clinical practice guidelines in oncology. Hepatobiliary cancers. 2008. http://www.nccn.org/professionals/physician_gls/PDF/hepatobiliary.pdf. Accessed 17 December 2007.
  22. 22.
    Yamada T, Alpers DH, Lane L, Owyang C, Powell DW, editors. Textbook of gastroenterology. 4th ed. Philadelphia: Lippincott, Williams & Wilkins; 2003 May 1. Chapter 118.Google Scholar
  23. 23.
    HAYES Medical Technology Directory™. Chemoembolization for Primary Liver Cancer. Lansdale, PA: HAYES, Inc.; ©2003 Winifred S. Hayes, Inc. Originally published Jul 12, 2002. Update Search Apr 9, 2007.Google Scholar
  24. 24.
    Libbrecht L, Desmet V, Van Damme B, Roskams T. The immunohistochemical phenotype of dysplastic foci in human liver: correlation with putative progenitor cells. J Hepatol. 2000;33:76–84.PubMedGoogle Scholar
  25. 25.
    Almeida-Porada G, Porada CD, Chamberlain J, Torabi A, Zanjani ED. Formation of human hepatocytes by human hematopoietic stem cells in sheep. Blood. 2004;104:2582–90.PubMedGoogle Scholar
  26. 26.
    Sakaida I, Terai S, Yamamoto N, Aoyama K, Ishikawa T, Nishina H, et al. Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice. Hepatology. 2004;40:1304–11.PubMedGoogle Scholar
  27. 27.
    am Esch 2nd JS, Knoefel WT, Klein M, Ghodsizad A, Fürst G, Poll LW, et al. Portal application of autologous CD133+ bone marrow cells to the liver: a novel concept to support hepatic regeneration. Stem Cells. 2005;23(4):463–70.PubMedGoogle Scholar
  28. 28.
    Zhu AX, Duda DG, Sahani DV, Jain RK. Development of sunitinib in hepatocellular carcinoma: rationale, early clinical experience, and correlative studies. Cancer J 2009; 15(4): 263–68Google Scholar
  29. 29.
    Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedGoogle Scholar
  30. 30.
    Sacco R, Bertini M, Petruzzi P, Bertoni M, Bargellini I, Bresci G, et al. Clinical impact of selective transarterial chemoembolization on hepatocellular carcinoma: a cohort study. World J Gastroenterol. 2009;15(15):1843–8.PubMedGoogle Scholar
  31. 31.
    Hao MZ, Chen Q, Lin HL, Wu H, Chen Q-Z, Li J-C, Zheng J-X, Ye Y-B. Comparison of intra-arterial chemotherapy with gemcitabine or floxuridine followed by TACE with oxaliplatine. Hepatitis Monthly 2009; 9(4): 253–60Google Scholar
  32. 32.
    Fürst G, Schulte am Esch J, Poll LW, Hosch SB, Fritz LB, Klein M, et al. Portal vein embolization and autologous CD133+ bone marrow stem cells for liver regeneration: initial experience. Radiology. 2007;243:171–9.PubMedGoogle Scholar
  33. 33.
    Takayasu K, Arii S, Ikai I, Omata M, Okita K, Ichida T, et al. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology. 2006;131:461–9.PubMedGoogle Scholar
  34. 34.
    Huo T-I, Huang Y-H, Wu J-C, Lee P-C, Chang F-Y, Lee S-D. Induction of complete tumor necrosis may reduce intrahepatic metastasis and prolong survival in patients with hepatocellular carcinoma undergoing locoregional therapy: a prospective study. Ann Oncol. 2004;15(5):775–80.PubMedGoogle Scholar
  35. 35.
    Chan AO, Yuen MF, Hui CK, et al. A prospective study regarding the complications of transcatheter intraarterial lipiodol chemoembolization in patients with hepatocellular carcinoma. Cancer. 2002;94(6):1747–52.PubMedGoogle Scholar
  36. 36.
    Fujii H, Hirose T, Oe S, et al. Contribution of bone marrow cells to liver regeneration after partial hepatectomy in mice. J Hepatol. 2002;36:653–9.PubMedGoogle Scholar
  37. 37.
    Theise ND, Badve S, Saxena R, et al. Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation. Hepatology. 2000;31:235–40.PubMedGoogle Scholar
  38. 38.
    De Silvestro G, Vicarioto M, Donadel C, et al. Mobilization of peripheral blood hematopoietic stem cells following liver resection surgery. Hepatogastroenterology. 2004;51:805–10.PubMedGoogle Scholar
  39. 39.
    Forbes SJ, Vig P, Poulsom R, et al. Bone marrow-derived liver stem cells: their therapeutic potential. Gastroenterology. 2002;123:654–5.PubMedGoogle Scholar
  40. 40.
    Ghodsizad A, Klein H-M, Borowski A, et al. Intraoperative isolation and processing of bone marrow derived stem cell. Cytotherapie. 2004;6:523–6.Google Scholar
  41. 41.
    Gehling UM, Willems M, Schlagner K, et al. Partial hepatectomy induces mobilization of a distinct population of progenitor cells in healthy liver donors. J Hepatol. 2004;40:19.Google Scholar
  42. 42.
    Wang X, Ge S, McNamara G, et al. Albumin-expressing hepatocyte-like cells develop in the livers of immune-deficient mice that received transplants of highly purified human hematopoietic stem cells. Blood. 2003;101:4201–8.PubMedGoogle Scholar
  43. 43.
    Sakaida I. Autologous bone marrow cell infusion therapy for liver cirrhosis. J Gastroenterol Hepatol 2008; 23(9): 1349–53Google Scholar
  44. 44.
    Kallis YN, Alison MR, Forbes SJ. Bone marrow stem cells and liver disease. Gut 2007;56: 716–24Google Scholar
  45. 45.
    Lazarus HM, Haynesworth SE, Gerson SL, Rosenthal NS, Caplan AI. Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use. Bone Marrow Transplant. 1995;16(4):557–64.PubMedGoogle Scholar
  46. 46.
    Koc ON, Gerson SL, Cooper BW, Dyhouse SM, Haynesworth SE, Caplan AI, et al. Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol. 2000;18(2):307–16.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Alaa Ismail
    • 1
  • Ahmed AlDorry
    • 2
  • Mohammed Shaker
    • 2
  • Reda Elwekeel
    • 1
  • Khaled Mokbel
    • 1
  • Doaa Zakaria
    • 3
  • Anas Meshaal
    • 1
  • Firas Zahr ElDeen
    • 1
  • Abdulhafez Selim
    • 4
  1. 1.Surgery Department, Faculty of MedicineAin Shams UniversityCairoEgypt
  2. 2.Radiology Department, Faculty of MedicineAin Shams UniversityCairoEgypt
  3. 3.Tropical Medicine Department, Faculty of MedicineAin Shams UniversityCairoEgypt
  4. 4.Osteotech Inc.EatontownUSA

Personalised recommendations