Bone Reconstruction Utilizing Mesenchymal Stem Cell Sheets for Cell Delivery

  • Zou Xiao Hui
  • Shen Wei Liang
  • Boon Chin Heng
  • Ouyang Hong Wei
Part of the Stem Cells and Cancer Stem Cells book series (STEM, volume 5)


Large bone defects often arise from traumatic injury. Mesenchymal stem cells (MSCs) hold great potential for bone regeneration. However to date, MSCs have not yet been incorporated into structural bone allografts in clinical practice. MSCs possess high proliferative capacity and the potential to differentiate into at least three mesodermal lineages – bone, cartilage and fat. The high proliferative capacity of bMSCs enables a more rapid formation of cell sheets compared to terminally differentiated cell types. The multi-lineage differentiation potential of MSCs broadens the application of the cell sheet technique, providing a wider scope of application for connective tissue engineering. In particular, assembly of MSC sheets and large allografts provides a convenient and practical tissue engineering platform for clinical regeneration of large musculoskeletal defects. This is anticipated to be a major future direction for enhancing allograft healing and repair via tissue engineering and stem cell engraftment.


Bone Graft Bone Tissue Engineering Cell Sheet Demineralized Bone Matrix Large Bone Defect 
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  1. Arinzeh TL, Tran T, Mcalary J, Daculsi G (2005) A comparative study of biphasic calcium phosphate ceramics for human mesenchymal stem-cell-induced bone formation. Biomaterials 26:3631–3638PubMedCrossRefGoogle Scholar
  2. Choi Y, Oldenburg FP, Sage L, Johnstone B, Yoo JU (2007) A bridging demineralized bone implant facilitates posterolateral lumbar fusion in New Zealand white rabbits. Spine (Phila Pa 1976) 32:36–41CrossRefGoogle Scholar
  3. Colton CK (1995) Implantable biohybrid artificial organs. Cell Transplant 4:415–436PubMedCrossRefGoogle Scholar
  4. De Bari C, Dell’Accio F, Karystinou A, Guillot PV, Fisk NM, Jones EA, McGonagle D, Khan IM, Archer CW, Mitsiadis TA, Donaldson AN, Luyten FP, Pitzalis C (2008) A biomarker-based mathematical model to predict bone-forming potency of human synovial and periosteal mesenchymal stem cells. Arthritis Rheum 58:240–250PubMedCrossRefGoogle Scholar
  5. Dennis JE, Esterly K, Awadallah A, Parrish CR, Poynter GM, Goltry KL (2007) Clinical-scale expansion of a mixed population of bone-marrow-derived stem and progenitor cells for potential use in bone-tissue regeneration. Stem Cells 25:2575–2582PubMedCrossRefGoogle Scholar
  6. Emery SE, Brazinski MS, Koka A, Bensusan JS, Stevenson S (1994) The biological and biomechanical effects of irradiation on anterior spinal bone grafts in a canine model. J Bone Joint Surg Am 76:540–548PubMedGoogle Scholar
  7. Fox EJ, Hau MA, Gebhardt MC, Hornicek FJ, Tomford WW, Mankin HJ (2002) Long-term followup of proximal femoral allografts. Clin Orthop Relat Res 397:106–113PubMedCrossRefGoogle Scholar
  8. Gray JC, Elves MW (1982) Donor cells’ contribution to osteogenesis in experimental cancellous bone grafts. Clin Orthop Relat Res 163:261–271PubMedGoogle Scholar
  9. Gurevitch O, Kurkalli BG, Prigozhina T, Kasir J, Gaft A, Slavin S (2003) Reconstruction of cartilage, bone, and hematopoietic microenvironment with demineralized bone matrix and bone marrow cells. Stem Cells 21:588–597PubMedCrossRefGoogle Scholar
  10. Kadiyala S, Young RG, Thiede MA, Bruder SP (1997) Culture expanded canine mesenchymal stem cells possess osteochondrogenic potential in vivo and in vitro. Cell Transplant 6:125–134PubMedCrossRefGoogle Scholar
  11. Karaoglu S, Baktir A, Kabak S, Arasi H (2002) Experimental repair of segmental bone defects in rabbits by demineralized allograft covered by free autogenous periosteum. Injury 33:679–683PubMedCrossRefGoogle Scholar
  12. Krampera M, Pizzolo G, Aprili G, Franchini M (2006) Mesenchymal stem cells for bone, cartilage, tendon and skeletal muscle repair. Bone 39:678–683PubMedCrossRefGoogle Scholar
  13. Mauney JR, Jaquiery C, Volloch V, Heberer M, Martin I, Kaplan DL (2005) In vitro and in vivo evaluation of differentially demineralized cancellous bone scaffolds combined with human bone marrow stromal cells for tissue engineering. Biomaterials 26:3173–3185PubMedCrossRefGoogle Scholar
  14. Mygind T, Stiehler M, Baatrup A, Li H, Zou X, Flyvbjerg A, Kassem M, Bunger C (2007) Mesenchymal stem cell ingrowth and differentiation on coralline hydroxyapatite scaffolds. Biomaterials 28:1036–1047PubMedCrossRefGoogle Scholar
  15. Ouyang HW, Goh JC, Lee EH (2004) Use of bone marrow stromal cells for tendon graft-to-bone healing: histological and immunohistochemical studies in a rabbit model. Am J Sports Med 32:321–327PubMedCrossRefGoogle Scholar
  16. Pouliot R, Larouche D, Auger FA, Juhasz J, Xu W, Li H, Germain L (2002) Reconstructed human skin produced in vitro and grafted on athymic mice. Transplantation 73:1751–1757PubMedCrossRefGoogle Scholar
  17. Stevenson S (1999) Biology of bone grafts. Orthop Clin North Am 30:543–552PubMedCrossRefGoogle Scholar
  18. Stevenson S, Li XQ, Davy DT, Klein L, Goldberg VM (1997) Critical biological determinants of incorporation of non-vascularized cortical bone grafts. Quantification of a complex process and structure. J Bone Joint Surg Am 79:1–16PubMedCrossRefGoogle Scholar
  19. Uebersax L, Hagenmuller H, Hofmann S, Gruenblatt E, Muller R, Vunjak-Novakovic G, Kaplan DL, Merkle HP, Meinel L (2006) Effect of scaffold design on bone morphology in vitro. Tissue Eng 12:3417–3429PubMedCrossRefGoogle Scholar
  20. Vilquin JT, Rosset P (2006) Mesenchymal stem cells in bone and cartilage repair: current status. Regen Med 1:589–604PubMedCrossRefGoogle Scholar
  21. Xin X, Hussain M, Mao JJ (2007) Continuing differentiation of human mesenchymal stem cells and induced chondrogenic and osteogenic lineages in electrospun PLGA nanofiber scaffold. Biomaterials 28:316–325PubMedCrossRefGoogle Scholar
  22. Yaszemski MJ, Payne RG, Hayes WC, Langer R, Mikos AG (1996) Evolution of bone transplantation: molecular, cellular and tissue strategies to engineer human bone. Biomaterials 17:175–185PubMedCrossRefGoogle Scholar
  23. Zhang X, Xie C, Lin AS, Ito H, Awad H, Lieberman JR, Rubery PT, Schwarz EM, O’Keefe RJ, Guldberg RE (2005) Periosteal progenitor cell fate in segmental cortical bone graft transplantations: implications for functional tissue engineering. J Bone Miner Res 20:2124–2137PubMedCrossRefGoogle Scholar
  24. Zund G, Ye Q, Hoerstrup SP, Schoeberlein A, Schmid AC, Grunenfelder J, Vogt P, Turina M (1999) Tissue engineering in cardiovascular surgery: MTT, a rapid and reliable quantitative method to assess the optimal human cell seeding on polymeric meshes. Eur J Cardiothorac Surg 15:519–524PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Zou Xiao Hui
    • 1
  • Shen Wei Liang
    • 1
  • Boon Chin Heng
    • 1
  • Ouyang Hong Wei
    • 1
  1. 1.#39 Center for Stem Cell and Tissue engineering, School of MedicineZhejiang UniversityHangzhouPeople’s Republic of China

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