Role of allogenic mesenchymal stem cells in the reconstruction of bone defect in rabbits

  • Hadisoebroto D. Ismail Department of Orthopaedic and Traumatology, Faculty of Medicine, Universitas Indonesia, Jakarta
  • Phedy Phedy Department of Orthopaedy and Traumatology, Faculty of Medicine, Universitas Indonesia, Jakarta
  • Erica Kholinne Department of Orthopaedy and Traumatology, Faculty of Medicine, Universitas Indonesia, Jakarta
  • Achmad A. Jusuf Department of Histology, Faculty of Medicine, Universitas Indonesia, Jakarta
  • Nyimas D. Yulisa Department of Radiology, Faculty of Medicine, Universitas Indonesia, Jakarta
Abstract viewed: 981 times
PDF downloaded: 602 times


Background: Despite the advancement of bone reconstruction in the past decade, large bone defect remains a challenge for orthopedic surgery. As mesenchymal stem cells (MSCs) emerges as one of the possible treatment of these defects, we evaluate the effect of its transplantation, particularly in combination with hydroxyapatite-calcium sulphate pellets.

Methods: Twenty eight rabbits were randomly assigned into four different treatment groups. Each group received a different type of grafts (Autograft, hydroxyapatite-calcium sulphate [HA-CaSO4], HA-CaSO4 combined with marrow aspirate, or HA-CaSO4 combined with 2x106 MSCs). One centimeter long bone defects were created then immediately fixated with mini plate-screw and two cerclage wires. It was followed by the graft transplantation. Callus thickness was measured from the x-rays taken at 4, 8, 12 week after transplantation by two authors working independently. At the end of the study, histological staining along with osteocyte index were obtained by sacrificing the rabbits. These data were analyzed by one-way ANOVA test.

Results: At the fourth week, callus thickness showed significant difference (p = 0.018). Although statistically insignificant, callus in MSCs group at the eighth week seemed to be thicker than any other groups of intervention (p = 0.546). The MSCs group also tend to have a higher osteocyte index at the follow-up weeks.

Conclusion: MSC transplantation on bone defect results in faster callus formation and tends to generate a thicker callus.

Keywords: bone defect, callus thickness, hydroxyapatite-calcium sulphate, mesenchymal stem cells, osteocyte index


  1. Arinzeh TL, Peter SJ, Archambault MP, van den Bos C, Gordon S, Kraus K, et al. Allogenic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect. J Bone Joint Surg Am. 2003;85A(10):1927-35.

  2. Muschler GF, Nakamoto C, Girrfith LG. Engineering principles of clinical cell-based tissue engineering. J Bone Joint Surg Am. 2004;86A(7):1541-58.

  3. DeCoster TA, Gehlert RJ, Mikola EA, Pirela-Cruz MA. Management of posttraumatic segmental bone defects. J Am Acad Orthop Surg. 2004;12(1):28-38.

  4. Bruder SP, Jaiswal N, Ricalton NS, Mosca JD, Kraus KH, Kadiyala S. Mesenchymal stem cells in osteobiology and applied bone regeneration. Clin Orthop Relat Res. 1998;355S:S247-56.

  5. Lee EH, Hui JHP. The potential of stem cells in orthopaedic surgery. J Bone Joint Surg Br. 2006;88(7):841-51.

  6. Hee HT, Ismail HD, Lim CT, Goh JC, Wong HK. Effects of implantation of bone marrow mesenchymal stem cells, disc distraction and combined therapy on reversing disc degeneration of the intervertebral disc. J Bone Joint Surg Br. 2010;92(5):726-36.

  7. Gainnoudis PV, Einhorn TA, Marsh D. Fracture healing: the diamond concept. Injury. 2007;38(Suppl 4):S3-6.

  8. De Long WG Jr, Einhorn TA, Koval K, McKee M, Smith W, Sanders R, et al. Bone grafts and bone graft substitutes in orthopaedic trauma surgery. A Critical analysis. J Bone Joint Surg Am. 2007;89(3):649-58.

  9. Kelly CM, Wilkins RM, Gitelis S, Hartjen C, Watson JT, Kim PT. The use of a surgical grade calcium sulfate as a bone graft substitute: results of a multicenter trial. Clin Orthop Rel Res. 2001;382:42-50.

  10. Rauschmann MA, Wichelhaus TA, Stirnal V, Dingeldein E, Zichner L, Schnettler R, et al. Nanocrystalline hydroxyapatite and calcium sulphate as biodegradable composite carrier material for local delivery of antibiotics in bone infections. Biomaterials. 2005;26(15):2677-84.

  11. Both SK, van der Muijsenberg AJ, van Blitterswijk CA, de Boer J, de Bruijn JD. A rapid and efficient method for expansion of human mesenchymal stem cells. Tissue Eng. 2007;13(1):3-9.

  12. Colter DC, Class R, DiGirolamo CM, Prockop DJ. Rapid expansion of recycling stem cells in cultures of plastic-adherent cells from human bone marrow. PNAS. 2000;97(7):3213-8.

  13. Pal R, Hanwate M, Jan M, Totey S. Phenotypic and functional comparison of optimum culture conditions for upscaling of bone marrow-derived mesenchymal stem cells. J Tissue Eng Regen Med. 2009;3(3):163-74.

  14. Wagner W, Bork S, Lepperdinger G, Joussen S, Ma N, Strunk D, et al. How to track cellular aging of mesenchymal stromal cells? Aging. 2010;2(4):224-30.

  15. Røsland GV, Svendsen A, Torsvik A, Sobala E, McCormack E, Immervoll H, et al. Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation. Cancer Res. 2009;69(13):5531-9.

  16. Bernardo ME, Zaffaroni N, Novara F, Cometa AM, Avanzini MA, Moretta A, et al. Human bone marrow–derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exhibit telomere maintenance mechanisms. Cancer Res. 2007;67(19):9142-9.

  17. Eastaugh-Waring SJ, Joslin CC, Hardy JR, Cunningham JL. Quantification of fracture healing from radiographs using the maximum callus index. Clin Orthop Relat Res. 2009; 467(8):1986-91.

  18. Nather A, David V, Teng JW, Lee CW, Pereira BP. Effect of autologous mesenchymal stem cells on biological healing of allografts in critical-sized tibial defects stimulated in adult rabbits. Ann Acad Med Singapore. 2010;39(8):599-606.

  19. Salter RB. Fractures and joint injuries-general features. In: Salter RB, ed. Textbook of disorders and injuries of the musculoskeletal system. Third ed. Maryland: William&Wilkins; 1999. p. 417-97.

  20. Yoo JU, Johnstone B. The role of osteochondral progenitor cells in fracture repair. Clin Orthop Relat Res. 1998;355S:S73-81.

How to Cite
Ismail HD, Phedy P, Kholinne E, Jusuf AA, Yulisa ND. Role of allogenic mesenchymal stem cells in the reconstruction of bone defect in rabbits. Med J Indones [Internet]. 2014Mar.11 [cited 2024May19];23(1):9-14. Available from:
Basic Medical Research