Clinical Orthopaedics and Related Research®

, Volume 468, Issue 10, pp 2725–2733

Shed Blood-derived Cells from Total Hip Arthroplasty Have Osteoinductive Potential: A Pilot Study

  • Tomokazu Yoshida
  • Masakazu Ishikawa
  • Yuji Yasunaga
  • Takuma Yamasaki
  • Mitsuo Ochi
Basic Research



Cell therapy using autologous cells has been used in the treatment of various medical conditions. The mononuclear cell (MNC) fraction of bone marrow (BM) contains stem/progenitor cells that could contribute to osteogenesis and angiogenesis.


We asked whether MNCs derived from intraoperative shed blood (SB), consisting of peripheral blood and BM, have osteoinductive and angiogenic potential.


We harvested SB and BM from six patients undergoing THA. Isolated MNCs from SB and BM were analyzed by flow cytometry to evaluate the CD34+ cell fraction and 1 × 106 cells were seeded on an interconnective porous calcium hydroxyapatite ceramic (IP-CHA) and transplanted in the backs of athymic rats. IP-CHAs without cells were transplanted as controls and all composites were harvested after 4 and 8 weeks. Osteoinductive potential was evaluated by histologic observation, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) using anti-osteocalcin (OC) antibodies qualitatively and quantitatively. To evaluate angiogenic potential, capillary density was measured by immunohistochemistry using Isolectin B4 4 weeks after implantation.


We found that CD34+ cells existed in SB-MNCs and there was a trend toward lower frequency compared with BM-MNCs. Histologic osteoinduction, OC expression, and capillary density were increased by transplantation of MNCs from SB. Similar results were achieved with MNCs from BM.


MNCs from SB have equivalent osteoinductive and angiogenic potential compared with those from BM.

Clinical Relevance

SB could be an attractive source for isolation of MNCs, enhancing osteoinduction and neovascularization, to augment the reconstruction of skeletal defects.


  1. 1.
    Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275:964–967.CrossRefPubMedGoogle Scholar
  2. 2.
    Bartsch T, Brehm M, Zeus T, Strauer BE. Autologous mononuclear stem cell transplantation in patients with peripheral occlusive arterial disease. J Cardiovasc Nurs. 2006;21:430–432.PubMedGoogle Scholar
  3. 3.
    Beverley PC, Linch D, Delia D. Isolation of human haematopoietic progenitor cells using monoclonal antibodies. Nature. 1980;287:332–333.CrossRefPubMedGoogle Scholar
  4. 4.
    Bolland BJ, Tilley S, New AM, Dunlop DG, Oreffo RO. Adult mesenchymal stem cells and impaction grafting: a new clinical paradigm shift. Expert Rev Med Devices. 2007;4:393–404.CrossRefPubMedGoogle Scholar
  5. 5.
    Bragdon CR, Doherty AM, Rubash HE, Jasty M, Li XJ, Seeherman H, Harris WH. The efficacy of BMP-2 to induce bone ingrowth in a total hip replacement model. Clin Orthop Relat Res. 2003;417:50–61.PubMedGoogle Scholar
  6. 6.
    Eghbali-Fatourechi GZ, Lamasam J, Fraser D. Circulating osteoblast-lineage cells. N Engl J Med. 2005;352:1959–1966.CrossRefPubMedGoogle Scholar
  7. 7.
    Gangji V, Hauzeur JP, Matos C, De Maertelaer V, Toungouz M, Lambermont M. Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells: a pilot study. J Bone Joint Surg Am. 2004;86:1153–1160.PubMedGoogle Scholar
  8. 8.
    Hernigou P, Beaujean F. Treatment of osteonecrosis with autologous bone marrow grafting. Clin Orthop Relat Res. 2002;405:14–23.CrossRefPubMedGoogle Scholar
  9. 9.
    Iwasaki H, Kawamoto A, Ishikawa M, Oyamada A, Nakamori S, Nishimura H, Sadamoto K, Horii M, Matsumoto T, Murasawa S, Shibata T, Suehiro S, Asahara T. Dose-dependent contribution of CD34-positive cell transplantation to concurrent vasculogenesis and cardiomyogenesis for functional regenerative recovery after myocardial infarction. Circulation. 2006;113:1311–1325.CrossRefPubMedGoogle Scholar
  10. 10.
    Jasty M, Harris WH. Salvage total hip reconstruction in patients with major acetabular bone deficiency using structural femoral head allografts. J Bone Joint Surg Br. 1990;72:63–67.PubMedGoogle Scholar
  11. 11.
    Kerboull M, Hamadouche M, Kerboull L. The Kerboull acetabular reinforcement device in major acetabular reconstructions. Clin Orthop Relat Res. 2000;378:155–168.CrossRefPubMedGoogle Scholar
  12. 12.
    Kitamura S, Ohgushi H, Hirose M, Funaoka H, Takakura Y, Ito H. Osteogenic differentiation of human bone marrow-derived mesenchymal cells cultured on alumina ceramics. Artif Organs. 2004;28:72–82.CrossRefPubMedGoogle Scholar
  13. 13.
    Korda M, Blunn G, Goodship A, Hua J. Use of mesenchymal stem cells to enhance bone formation around revision hip replacements. J Orthop Res. 2008;26:880–885.CrossRefPubMedGoogle Scholar
  14. 14.
    Mahomed NN, Barrett JA, Katz JN, Phillips CB, Losina E, Lew RA, Guadagnoli E, Harris WH, Poss R, Baron JA. Rates and outcomes of primary and revision total hip replacement in the United States Medicare population. J Bone Joint Surg Am. 2003;85:27–32.PubMedGoogle Scholar
  15. 15.
    Matsumoto T, Kawamoto A, Kuroda R, Ishikawa M, Mifune Y, Iwasaki H, Miwa M, Horii M, Hayashi S, Oyamada A, Nishimura H, Murasawa S, Doita M, Kurosaka M, Asahara T. Therapeutic potential of vasculogenesis and osteogenesis promoted by peripheral blood CD34-positive cells for functional bone healing. Am J Pathol. 2006;169:1440–1457.CrossRefPubMedGoogle Scholar
  16. 16.
    Ohgushi H, Goldberg VM, Caplan AI. Heterotopic osteogenesis in porous ceramics induced by marrow cells. J Orthop Res. 1989;7:568–578.CrossRefPubMedGoogle Scholar
  17. 17.
    Ohgushi H, Kitamura S, Kotobuki N, Hirose M, Machida H, Muraki K, Takakura Y. Clinical application of marrow mesenchymal stem cells for hard tissue repair. Yonsei Med J. 2004;45:61–67.PubMedGoogle Scholar
  18. 18.
    Oonishi H, Iwaki Y, Kin N, Kushitani S, Murata N, Wakitani S, Imoto K. Hydroxyapatite in revision of total hip replacements with massive acetabular defect. J Bone Joint Surg Br. 1997;79:87–92.CrossRefPubMedGoogle Scholar
  19. 19.
    Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–147.CrossRefPubMedGoogle Scholar
  20. 20.
    Porter RM, Liu F, Pilapil C, Betz OB, Vrahas MS, Harris MB, Evans CH. Osteogenic potential of reamer irrigator aspirator (RIA) aspirate collected from patients undergoing hip arthroplasty. J Orthop Res. 2009;27:42–49.CrossRefPubMedGoogle Scholar
  21. 21.
    Rehman J, Li J, Orschell CM, March KL. Peripheral blood ‘endothelial progenitor cells’ are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation. 2003;107:1164–1169.CrossRefPubMedGoogle Scholar
  22. 22.
    Tamai N, Myoui A, Tomita T, Nakase T, Tanaka J, Ochi T, Yoshikawa H. Novel hydroxyapatite ceramics with an interconnective porous structure exhibit superior osteoconduction in vivo. J Biomed Mater Res. 2002;59:110–117.CrossRefPubMedGoogle Scholar
  23. 23.
    Ukai R, Honmou O, Harada K, Houkin K, Hamada H, Kocsis JD. Mesenchymal stem cells derived from peripheral blood protects against ischemia. J Neurotrauma. 2007;24:508–520.CrossRefPubMedGoogle Scholar
  24. 24.
    Yamasaki T, Yasunaga Y, Terayama H, Ito Y, Ishikawa M, Adachi N, Ochi M. Transplantation of bone marrow mononuclear cells enables simultaneous treatment with osteotomy for osteonecrosis of the bilateral femoral head. Med Sci Monit. 2008;14:C23–C30.Google Scholar
  25. 25.
    Yoshikawa T, Ohgushi H, Okumura M, Tamai S, Dohi Y, Moriyama T. Biochemical and histological sequences of membranous ossification in ectopic site. Calcif Tissue Int. 1992;50:184–188.CrossRefPubMedGoogle Scholar
  26. 26.
    Zhao Q, Sun Y, Xia L, Chen A, Wang Z. Randomized study of mononuclear bone marrow cell transplantation in patients with coronary surgery. Ann Thorac Surg. 2008;86:1833–1840.CrossRefPubMedGoogle Scholar

Copyright information

© The Association of Bone and Joint Surgeons® 2010

Authors and Affiliations

  • Tomokazu Yoshida
    • 1
  • Masakazu Ishikawa
    • 1
  • Yuji Yasunaga
    • 2
  • Takuma Yamasaki
    • 1
  • Mitsuo Ochi
    • 1
  1. 1.Department of Orthopaedic Surgery, Graduate School of Biomedical SciencesHiroshima UniversityHiroshimaJapan
  2. 2.Department of Artificial Joints and Biomaterials, Graduate School of Biomedical SciencesHiroshima UniversityHiroshimaJapan

Personalised recommendations