Tumor Biology

, Volume 34, Issue 4, pp 2161–2168 | Cite as

Effect of bone marrow mesenchymal stem cells on hepatocellular carcinoma in microcirculation

  • Peng Gong
  • Yingxin Wang
  • Yulin Wang
  • Shi Jin
  • Haifeng Luo
  • Jing Zhang
  • Haidong Bao
  • Zhongyu Wang
Research Article


This study aims t explore the effect and application of bone marrow mesenchymal stem cells (BMSCs) on hepatocellular carcinoma in microcirculation by observing the angiogenesis of hepatocellular carcinoma in transplanted area. BMSCs were isolated and cultured primarily using the method of whole bone marrow culture and identifying surface antigens of third-generation bone marrow-derived mesenchymal stem cells using flow cytometry. Hepatoma cells cultured with BMSCs-conditioned medium (BMSCs-CM) were assayed using the cell proliferation rate of the MTT method. Nude mice were divided into control group (group A), BMSCs cell transplantation group (group B), HepG-2 cell group (group C), and combined BMSCs and HepG-2 cell cotransplanted group (group D). The result showed that the microvascular density was not significantly different in groups A and B. However, the microvascular density at 14 days was higher than 0 day in group C (P < 0.05). In group D, the microvascular density at 14 days was higher than that of 7 and 0 days (P < 0.05) and 7 days was higher than 0 days (P < 0.05). It was showed that the microvascular density did not get significant difference at 0 and 7 days in the four groups (P > 0.05). But the microvascular density of group C was higher than groups A and B at 14 days (P < 0.05), group D was higher than groups A and B at 14 days (P < 0.05) and group D was higher than group C at 14 days (P < 0.05). BMSCs could promote the growth of microvascular in hepatoma cells in a transplanted area.


Primary hepatocellular carcinoma BMSCs Dorsal skinfold chamber Microcirculation 


  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.PubMedCrossRefGoogle Scholar
  2. 2.
    Stat bite. Worldwide cervical and uterine cancer incidence and mortality, 2002. J Natl Cancer Inst. 2006;98(15):1031.CrossRefGoogle Scholar
  3. 3.
    Colella G, Bottelli R, De Carlis L, Sansalone CV, Rondinara GF, Alberti A, et al. Hepatocellular carcinoma: comparison between liver transplantation, resective surgery, ethanol injection, and chemoembolization. Transpl Int. 1998;11 Suppl 1:S193–6.PubMedGoogle Scholar
  4. 4.
    van den Broek MA, Olde Damink SW, Dejong CH, Lang H, Malago M, Jalan R, et al. Liver failure after partial hepatic resection: definition, pathophysiology, risk factors and treatment. Liver Int. 2008;28(6):767–80.PubMedCrossRefGoogle Scholar
  5. 5.
    Ezzat TM, Dhar DK, Newsome PN, Malago M, Olde Damink SW. Use of hepatocyte and stem cells for treatment of post-resectional liver failure: are we there yet? Liver Int. 2011;31(6):773–84.PubMedCrossRefGoogle Scholar
  6. 6.
    Kisseleva T, Gigante E, Brenner DA. Recent advances in liver stem cell therapy. Curr Opin Gastroenterol. 2010;26(4):395–402.PubMedCrossRefGoogle Scholar
  7. 7.
    Hung SC, Deng WP, Yang WK, Liu RS, Lee CC, Su TC, et al. Mesenchymal stem cell targeting of microscopic tumors and tumor stroma development monitored by noninvasive in vivo positron emission tomography imaging. Clin Cancer Res. 2005;11(21):7749–56.PubMedCrossRefGoogle Scholar
  8. 8.
    Gibson-D'Ambrosio RE, Crowe DL, Shuler CE, D'Ambrosio SM. The establishment and continuous subculturing of normal human adult hepatocytes: expression of differentiated liver functions. Cell Biol Toxicol. 1993;9(4):385–403.PubMedCrossRefGoogle Scholar
  9. 9.
    Yagi H, Parekkadan B, Suganuma K, Soto-Gutierrez A, Tompkins RG, Tilles AW, et al. Long-term superior performance of a stem cell/hepatocyte device for the treatment of acute liver failure. Tissue Eng A. 2009;15(11):3377–88.CrossRefGoogle Scholar
  10. 10.
    Fagioli F, Berger M, Brach del Prever A, Lioji S, Aglietta M, Ferrari S, et al. Regression of metastatic osteosarcoma following non-myeloablative stem cell transplantation. A case report. Haematologica. 2003;88(5):ECR16.PubMedGoogle Scholar
  11. 11.
    Omuro Y, Matsumoto G, Sasaki T, Tanaka Y, Maeda Y, Sakamaki H, et al. Regression of an unresectable pancreatic tumor following nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. Bone Marrow Transplant. 2003;31(10):943–5.PubMedCrossRefGoogle Scholar
  12. 12.
    Djouad F, Plence P, Bony C, Tropel P, Apparailly F, Sany J, et al. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood. 2003;102(10):3837–44.PubMedCrossRefGoogle Scholar
  13. 13.
    Leek RD, Harris AL, Lewis CE. Cytokine networks in solid human tumors: regulation of angiogenesis. J Leukoc Biol. 1994;56(4):423–35.PubMedGoogle Scholar
  14. 14.
    Budhu A, Wang XW. The role of cytokines in hepatocellular carcinoma. J Leukoc Biol. 2006;80(6):1197–213.PubMedCrossRefGoogle Scholar
  15. 15.
    Matushansky I, Hernando E, Socci ND, Mills JE, Matos TA, Edgar MA, et al. Derivation of sarcomas from mesenchymal stem cells via inactivation of the Wnt pathway. J Clin Invest. 2007;117(11):3248–57.PubMedCrossRefGoogle Scholar
  16. 16.
    Poon RT, Fan ST, Lo CM, Liu CL, Lam CM, Yuen WK, et al. Improving perioperative outcome expands the role of hepatectomy in management of benign and malignant hepatobiliary diseases: analysis of 1222 consecutive patients from a prospective database. Ann Surg. 2004;240(4):698–708. discussion 708–610.PubMedGoogle Scholar
  17. 17.
    Fan ST, Lo CM, Liu CL, Lam CM, Yuen WK, Yeung C, et al. Hepatectomy for hepatocellular carcinoma: toward zero hospital deaths. Ann Surg. 1999;229(3):322–30.PubMedCrossRefGoogle Scholar
  18. 18.
    Theise ND, Nimmakayalu M, Gardner R, Illei PB, Morgan G, Teperman L, et al. Liver from bone marrow in humans. Hepatology. 2000;32(1):11–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Xu F, Shi J, Yu B, Ni W, Wu X, Gu Z. Chemokines mediate mesenchymal stem cell migration toward gliomas in vitro. Oncol Rep. 2010;23(6):1561–7.PubMedGoogle Scholar
  20. 20.
    Debergh I, Van Damme N, Pattyn P, Peeters M, Ceelen WP. The low-molecular-weight heparin, nadroparin, inhibits tumour angiogenesis in a rodent dorsal skinfold chamber model. Br J Cancer. 2010;102(5):837–43.PubMedCrossRefGoogle Scholar
  21. 21.
    Li CY, Shan S, Huang Q, Braun RD, Lanzen J, Hu K, et al. Initial stages of tumor cell-induced angiogenesis: evaluation via skin window chambers in rodent models. J Natl Cancer Inst. 2000;92(2):143–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Zhu W, Xu W, Jiang R, Qian H, Chen M, Hu J, et al. Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Exp Mol Pathol. 2006;80(3):267–74.PubMedCrossRefGoogle Scholar
  23. 23.
    Zhang B, Inagaki M, Jiang B, Miyakoshi M, Arikura J, Ogawa K, et al. Effects of bone marrow and hepatocyte transplantation on liver injury. J Surg Res. 2009;157(1):71–80.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Peng Gong
    • 1
  • Yingxin Wang
    • 1
  • Yulin Wang
    • 1
  • Shi Jin
    • 1
  • Haifeng Luo
    • 1
  • Jing Zhang
    • 1
  • Haidong Bao
    • 1
  • Zhongyu Wang
    • 1
  1. 1.Hepatobiliary SurgeryThe First Affiliated Hospital of Dalian Medical UniversityDalianChina

Personalised recommendations