Skip to main content
SpringerLink
Log in
Book cover

Regenerative Biology of the Spine and Spinal Cord pp 188–210Cite as

Progenitor Cells: Role and Usage in Bone Tissue Engineering Approaches for Spinal Fusion

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 760))

Abstract

Advancement of in vitro osteogenesis, or the production of bone, is a complex process that has significant clinical implications. Surgical intervention of several spinal disorders entails decompression of the spinal cord and nerves which can lead to subsequent biomechanical instability of the spine. Spinal arthrodesis (fusion) is often required to correct this instability and necessary to eliminate the resulting pathological motion of vertebral segments. Therefore, the achievement of proper spinal fusion, is a critical determinant of treatment efficacy. This chapter focuses on the molecular and cellular components that are involved in bone growth and healing. Mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) are the precursor cells essential for the formation of the five different types of bone cells: osteoprogenitor cells, osteoblasts, osteoclasts, osteocytes and lining cells. Similarly, endothelial progenitor cells (EPCs) differentiate into endothelial cells, which are essential in angiogenesis and neovascularization. MSCs tri-lineage potential (osteogenic, chondrogenic and adipogenic lineages) have made them the focus of most experimental approaches. Here, we describe their individual roles, as well as pose novel concepts on how their collective role may be the optimal strategy to improve upon in vitro osteogenesis and whether this could also be translated to improved bone formation in vivo. Further, we discuss the various molecular markers that are available for cell identification and the tissue engineering strategies that could replicate the osteoinductive, osteoconductive and osteoproductive milieu that is available in autograft. Finally, we present a broad primer on the possible integration of cellular, molecular and tissue engineering strategies to improve osteogenesis and the future trends that may bring the promise seen in the laboratory to fruition in preclinical animal models.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Frazer JES, Breathnach AS. Anatomy of the Human Skeleton, 6th ed. Boston: Little, Brown, 1965

    Google Scholar 

  2. Carlson BM. Human Embryology and Developmental Biology, 4th ed. Philadelphia: Mosby/Elsevier, 2009.

    Google Scholar 

  3. Bilezikian JP, Raisz LG, Rodan GA. Principles of Bone Biology, 2nd ed. San Diego: Academic Press, 2002.

    Google Scholar 

  4. Hall BK, Miyake T. All for one and one for all: condensations and the initiation of skeletal development. Bioessays 2000; 22:138–147.

    Article  CAS  PubMed  Google Scholar 

  5. Kanczler JM, Oreffo RO. Osteogenesis and angiogenesis: the potential for engineering bone. Eur Cell Mater 2008; 15:100–114.

    Article  CAS  PubMed  Google Scholar 

  6. Hermey DC, Marks SC. The structure and development of bone. In: Bilezikian JP, Raisz LG, Rodan GA, eds. Principles of Bone Biology. New York: Academic Press, 1996: 3–14.

    Google Scholar 

  7. McCarthy I. The physiology of bone blood flow: a review. J Bone Joint Surg Am 2006; 88 (Suppl 3):4–9.

    PubMed  Google Scholar 

  8. M’Gregor AN. The Repair of Bone, with special reference to Transplantation and other Artificial Aids. J Anat Physiol 1892; 26:220–230.

    CAS  Google Scholar 

  9. Brighton CT, Hunt RM. Early histologic and ultrastructural changes in microvessels of periosteal callus. J Orthop Trauma 1997; 11:244–253.

    Article  CAS  PubMed  Google Scholar 

  10. Turner CH, Wang T, Burr DB. Shear strength and fatigue properties of human cortical bone determined from pure shear tests. Calcif Tissue Int 2001; 69:373–378.

    Article  CAS  PubMed  Google Scholar 

  11. Hillier ML, Bell LS. Differentiating human bone from animal bone: a review of histological methods. J Forensic Sci 2007; 52, 249–263.

    Article  PubMed  Google Scholar 

  12. Sikavitsas VI, Temenoff JS, Mikos AG. Biomaterials and bone mechanotransduction. Biomaterials 2001; 22:2581–2593.

    Article  CAS  PubMed  Google Scholar 

  13. Rodan GA. Introduction to bone biology. Bone 1992; 13 (Suppl 1):S3–S6.

    Article  CAS  PubMed  Google Scholar 

  14. Field RA, Riley ML, Mello FC et al. Bone composition in cattle, pigs, sheep and poultry. J Anim Sci 1974; 39:493–499.

    Article  CAS  PubMed  Google Scholar 

  15. Legros R, Balmain N, Bonel G. Age-related changes in mineral of rat and bovine cortical bone. Calcif Tissue Int 1987; 41:137–144.

    Article  CAS  PubMed  Google Scholar 

  16. Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. Cancer Treat Res 2009; 152:3–13.

    Article  PubMed  Google Scholar 

  17. Miller S, Jee W. The bone lining cell: A distinct phenotype? Calcif Tissue Int 1987; 41:1–5.

    Article  CAS  PubMed  Google Scholar 

  18. Jethva R, Otsuru S, Dominici M et al. Cell therapy for disorders of bone. Cytotherapy 2009; 11:3–17.

    Article  CAS  PubMed  Google Scholar 

  19. Bar-Shavit Z. The osteoclast: a multinucleated, hematopoietic-origin, bone-resorbing osteoimmune cell. J Cell Biochem 2007; 102:1130–1139.

    Article  CAS  PubMed  Google Scholar 

  20. Nijweide PJ, Burger EH, Feyen JH. Cells of bone: proliferation, differentiation and hormonal regulation. Physiol Rev 1986; 66:855–886.

    Article  CAS  PubMed  Google Scholar 

  21. Khoo CP, Pozzilli P, Alison MR. Endothelial progenitor cells and their potential therapeutic applications. Regen Med 2008; 3:863–876.

    Article  CAS  PubMed  Google Scholar 

  22. Pittenger MF et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284:143–147.

    Article  CAS  PubMed  Google Scholar 

  23. Caplan AI. Mesenchymal stem cells. J Orthop Res 1991; 9:641–650.

    Article  CAS  PubMed  Google Scholar 

  24. Buono KD, Mitchel M, Wolenuk E et al. Endothelial progenitor cells. In: Stem Cell and Regenerative Medicine. New Jersey: Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, 2010. Available at: http://njms.umdnj.edu/gsbs/stemcell/scofthemonth/EPClay.html. Accessed 2011.

    Google Scholar 

  25. Bone Marrow Transplant. New York: Columbia University Medical Center, 2010. Available at: http:// www.cumc.columbia.edu/dept/medicine/bonemarrow/bmtinfo.html. Accessed 2011.

    Google Scholar 

  26. Liechty KW, MacKenzie TC, Shaaban AF et al. Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 2000; 6:1282–1286.

    Article  CAS  PubMed  Google Scholar 

  27. Dominici M, Pritchard C, Garlits JE et al. Hematopoietic cells and osteoblasts are derived from a common marrow progenitor after bone marrow transplantation. Proc Natl Acad Sci USA 2004; 101:11761–11766.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Friedenstein AJ, Chailakhyan RK, Latsinik NV et al. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation 1974; 17:331–340.

    Article  CAS  PubMed  Google Scholar 

  29. Karaöz E, Okçu A, Gacar G et al. A comprehensive characterization study of human bone marrow mscs with an emphasis on molecular and ultrastructural properties. J Cell Physiol 2011; 226:1367–1382.

    Article  PubMed  CAS  Google Scholar 

  30. Sotiropoulou PA, Papamichail M. Immune properties of mesenchymal stem cells. Methods Mol Biol 2007; 407:225–243.

    Article  CAS  PubMed  Google Scholar 

  31. Bielby R, Jones E, McGonagle D. The role of mesenchymal stem cells in maintenance and repair of bone. Injury 2007; 38(Suppl 1):S26–S32.

    Article  PubMed  Google Scholar 

  32. Haynesworth SE, Baber MA, Caplan AI. Cell surface antigens on human marrow-derived mesenchymal cells are detected by monoclonal antibodies. Bone 1992; 13:69–80.

    Article  CAS  PubMed  Google Scholar 

  33. Satija NK, Gurudutta GU, Sharma S et al. Mesenchymal stem cells: molecular targets for tissue engineering. Stem Cells Dev 2007; 16:7–23.

    Article  CAS  PubMed  Google Scholar 

  34. Conget PA, Minguell JJ. Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J Cell Physiol 1999; 181:67–73.

    Article  CAS  PubMed  Google Scholar 

  35. Wynn RF, Hart CA, Corradi-Perini C et al. A small proportion of mesenchymal stem cells strongly expresses functionally active CXCR4 receptor capable of promoting migration to bone marrow. Blood 2004; 104:2643–2645.

    Article  CAS  PubMed  Google Scholar 

  36. Chamberlain G, Fox J, Ashton B et al. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features and potential for homing. Stem Cells 2007; 25:2739–2749.

    Article  CAS  PubMed  Google Scholar 

  37. Zvaifler NJ et al. Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res 2000; 2:477–488.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Boquest AC, Shahdadfar A, Frønsdal K et al. Isolation and transcription profiling of purified uncultured human stromal stem cells: alteration of gene expression after in vitro cell culture. Mol Biol Cell 2005; 16:1131–1141.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Zuk PA, Zhu M, Ashjian P et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 2002; 13:4279–4295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. De Bari C, Dell’Accio F, Luyten FP. Human periosteum-derived cells maintain phenotypic stability and chondrogenic potential throughout expansion regardless of donor age. Arthritis Rheum 2001; 44:85–95.

    Article  PubMed  Google Scholar 

  41. De Bari C, Dell’Accio F, Tylzanowski P et al. Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum 2001; 44:1928–1942.

    Article  PubMed  Google Scholar 

  42. Le Blanc K. Immunomodulatory effects of fetal and adult mesenchymal stem cells. Cytotherapy 2003; 5:485–489.

    Article  CAS  PubMed  Google Scholar 

  43. Krampera M, Glennie S, Dyson J et al. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T-cells to their cognate peptide. Blood 2003; 101:3722–3729.

    Article  CAS  PubMed  Google Scholar 

  44. Di Nicola M, Carlo-Stella C, Magni M et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002; 99:3838–3843.

    Article  PubMed  Google Scholar 

  45. Le Blanc K, Tammik L, Sundberg B et al. Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol 2003; 57:11–20.

    Article  CAS  PubMed  Google Scholar 

  46. Dominici M, Le Blanc K, Mueller I et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8:315–317.

    Article  CAS  PubMed  Google Scholar 

  47. Jones EA, Kinsey SE, English A et al. Isolation and characterization of bone marrow multipotential mesenchymal progenitor cells. Arthritis Rheum 2002; 46:3349–3360.

    Article  PubMed  Google Scholar 

  48. Sotiropoulou PA, Perez SA, Papamichail M. Clinical grade expansion of human bone marrow mesenchymal stem cells. Methods Mol Biol 2007; 407:245–263.

    Article  CAS  PubMed  Google Scholar 

  49. Sekiya I, Larson BL, Smith JR et al. Expansion of human adult stem cells from bone marrow stroma: conditions that maximize the yields of early progenitors and evaluate their quality. Stem Cells 2002; 20:530–541.

    Article  PubMed  Google Scholar 

  50. Till JE, Mc CE. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res 1961; 14:213–222.

    Article  CAS  PubMed  Google Scholar 

  51. Duval W. Hematopoietic stem cells. In: Regenerative Medicine Report on Stem Cells. Bethesda: National Institutes of Health and Department of Health and Human Services, 2006.

    Google Scholar 

  52. Randall TD, Weissman IL. Phenotypic and functional changes induced at the clonal level in hematopoietic stem cells after 5-fluorouracil treatment. Blood 1997; 89:3596–3606.

    CAS  PubMed  Google Scholar 

  53. Wilson A, Trumpp A. Bone-marrow haematopoietic-stem-cell niches. Nat Rev Immunol 2006; 6, 93–106.

    Article  CAS  PubMed  Google Scholar 

  54. Kindler V, Suva D, Soulas C et al. Haematopoietic stem cells and mesenchymal stem cells as tools for present and future cellular therapies. Swiss Med Wkly 2006; 136:333–337.

    PubMed  Google Scholar 

  55. Amos TA, Gordon MY. Sources of human hematopoietic stem cells for transplantation—a review. Cell Transplant 1995; 4:547–569.

    CAS  PubMed  Google Scholar 

  56. Surbek DV et al. Developmental changes in adhesion molecule expressions in umbilical cord blood CD34 hematopoietic progenitor and stem cells. Am J Obstet Gynecol 2000; 183:1152–1157.

    Article  CAS  PubMed  Google Scholar 

  57. Smith C, Storms B. Hematopoietic stem cells. Clin Orthop Relat Res 2000; S91–S97.

    Article  Google Scholar 

  58. Dorrell C, Gan OI, Pereira DS et al. Expansion of human cord blood CD34(+)CD38(-) cells in ex vivo culture during retroviral transduction without a corresponding increase in SCID repopulating cell (SRC) frequency: dissociation of SRC phenotype and function. Blood 2000; 95:102–110.

    CAS  PubMed  Google Scholar 

  59. Chen W et al. Thrombopoietin cooperates with FLT3-ligand in the generation of plasmacytoid dendritic cell precursors from human hematopoietic progenitors. Blood 2004; 103:2547–2553.

    Article  CAS  PubMed  Google Scholar 

  60. Asahara T et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275:964–967.

    Article  CAS  PubMed  Google Scholar 

  61. Robb AO, Mills NL, Newby DE et al. Endothelial progenitor cells in pregnancy. Reproduction 2007; 133:1–9.

    Article  CAS  PubMed  Google Scholar 

  62. Jones CP, Rankin SM. Bone marrow-derived stem cells and respiratory disease. Chest 2011; 140:205–211.

    Article  CAS  PubMed  Google Scholar 

  63. Foresta C, De Toni L, Ferlin A et al. Clinical implication of endothelial progenitor cells. Expert Rev Mol Diagn 2010; 10:89–105.

    Article  PubMed  Google Scholar 

  64. Murohara T, Ikeda H, Duan J et al. Transplanted cord blood-derived endothelial precursor cells augment postnatal neovascularization. J Clin Invest 2000; 105:1527–1536.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Peichev M, Naiyer AJ, Pereira D et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 2000; 95:952–958.

    CAS  PubMed  Google Scholar 

  66. Majka SM, Jackson KA, Kienstra KA et al. Distinct progenitor populations in skeletal muscle are bone marrow derived and exhibit different cell fates during vascular regeneration. J Clin Invest 2003; 111:71–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Choi K, Kennedy M, Kazarov A et al. A common precursor for hematopoietic and endothelial cells. Development 1998; 125:725–732.

    CAS  PubMed  Google Scholar 

  68. Gehling UM, Ergün S, Schumacher U et al. In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood 2000; 95:3106–3112.

    CAS  PubMed  Google Scholar 

  69. Werner N, Kosiol S, Schiegl T et al. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 2005; 353:999–1007.

    Article  CAS  PubMed  Google Scholar 

  70. Case J, Mead LE, Bessler WK et al. Human CD34+AC133+VEGFR-2+ cells are not endothelial progenitor cells but distinct, primitive hematopoietic progenitors. Exp Hematol 2007; 35:1109–1118.

    Article  CAS  PubMed  Google Scholar 

  71. Ingram DA, Mead LE, Tanaka H et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood 2004; 104: 2752–2760.

    Article  CAS  PubMed  Google Scholar 

  72. Yoder MC, Ingram DA. Endothelial progenitor cell: ongoing controversy for defining these cells and their role in neoangiogenesis in the murine system. Curr Opin Hematol 2009; 16:269–273.

    Article  CAS  PubMed  Google Scholar 

  73. McNiece IK, Stewart FM, Deacon DM et al. Detection of a human CFC with a high proliferative potential. Blood 1989; 74:609–612.

    CAS  PubMed  Google Scholar 

  74. Clines GA. Prospects for osteoprogenitor stem cells in fracture repair and osteoporosis. Curr Opin Organ Transplant 2010; 15:73–78

    Article  PubMed  PubMed Central  Google Scholar 

  75. Mori-Akiyama Y, Akiyama H, Rowitch DH et al. Sox9 is required for determination of the chondrogenic cell lineage in the cranial neural crest. Proc Natl Acad Sci USA 2003; 100:9360–9365.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Tontonoz P, Hu E, Spiegelman BM. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 1994; 79:1147–1156.

    Article  CAS  PubMed  Google Scholar 

  77. Jones JR, Barrick C, Kim KA et al. Deletion of PPARgamma in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance. Proc Natl Acad Sci USA 2005; 102:6207–6212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Otto F, Thornell AP, Crompton T et al. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 1997; 89:765–771.

    Article  CAS  PubMed  Google Scholar 

  79. Heldin CH, Miyazono K, ten Dijke P. TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature 1997; 390:465–471.

    Article  CAS  PubMed  Google Scholar 

  80. Li B. Bone morphogenetic protein-Smad pathway as drug targets for osteoporosis and cancer therapy. Endocr Metab Immune Disord Drug Targets 2008; 8:208–219.

    Article  CAS  PubMed  Google Scholar 

  81. Lorenzo J, Choi Y. Osteoimmunology. Immunol Rev 2005; 208:5–6.

    Article  PubMed  Google Scholar 

  82. De Bari C, Kurth TB, Augello A. Mesenchymal stem cells from development to postnatal joint homeostasis, aging and disease. Birth Defects Res C Embryo Today 2010; 90:257–271.

    Article  PubMed  CAS  Google Scholar 

  83. Long MW. Osteogenesis and bone-marrow-derived cells. Blood Cells Mol Dis 2001; 27:677–690.

    Article  CAS  PubMed  Google Scholar 

  84. Long MW, Williams JL, and Mann KG. Expression of human bone-related proteins in the hematopoietic microenvironment. J Clin Invest 1990; 86:1387–1395.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Buckley KA, Fraser WD. Receptor activator for nuclear factor kappaB ligand and osteoprotegerin: regulators of bone physiology and immune responses/potential therapeutic agents and biochemical markers. Ann Clin Biochem 2002; 39:551–556.

    Article  CAS  PubMed  Google Scholar 

  86. Rho J, Altmann CR, Socci ND et al. Gene expression profiling of osteoclast differentiation by combined suppression subtractive hybridization (SSH) and cDNA microarray analysis. DNA Cell Biol 2002; 21:541–549.

    Article  CAS  PubMed  Google Scholar 

  87. Inoue J, Ishida T, Tsukamoto N et al. Tumor necrosis factor receptor-associated factor (TRAF) family: adapter proteins that mediate cytokine signaling. Exp Cell Res 2000; 254:14–24.

    Article  CAS  PubMed  Google Scholar 

  88. Gilmore TD. Introduction to NF-kappaB: players, pathways, perspectives. Oncogene 2006; 25:6680–6684.

    Article  CAS  PubMed  Google Scholar 

  89. Pearson G, Robinson F, Beers Gibson T et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 2001; 22:153–183.

    CAS  PubMed  Google Scholar 

  90. Wong BR, Josien R, Choi Y. TRANCE is a TNF family member that regulates dendritic cell and osteoclast function. J Leukoc Biol 1999; 65:715–724.

    Article  CAS  PubMed  Google Scholar 

  91. Anderson SK, Gibbs CP, Tanaka A et al. Human cellular src gene: nucleotide sequence and derived amino acid sequence of the region coding for the carboxy-terminal two-thirds of pp60c-src. Mol Cell Biol 1985; 5:1122–1129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Wong BR, Besser D, Kim N et al. TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src. Mol Cell 1999; 4:1041–1049.

    Article  CAS  PubMed  Google Scholar 

  93. Rafii S, Lyden D. Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat Med 2003; 9:702–712.

    Article  CAS  PubMed  Google Scholar 

  94. Heissig B, Hattori K, Dias S et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 2002; 109:625–637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Rae PC, Kelly RD, Egginton S et al. Angiogenic potential of endothelial progenitor cells and embryonic stem cells. Vasc Cell 2011; 3:11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Eliceiri BP, Cheresh DA. The role of alphav integrins during angiogenesis: insights into potential mechanisms of action and clinical development. J Clin Invest 1999; 103:1227–1230.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Hynes RO. A reevaluation of integrins as regulators of angiogenesis. Nat Med 2002; 8:918–921.

    Article  CAS  PubMed  Google Scholar 

  98. Wijelath ES, Murray J, Rahman S et al. Novel vascular endothelial growth factor binding domains of fibronectin enhance vascular endothelial growth factor biological activity. Circ Res 2002; 91:25–31.

    Article  CAS  PubMed  Google Scholar 

  99. Reid JJ, Johnson JS, Wang JC. Challenges to bone formation in spinal fusion. J Biomech 2011; 44:213–220.

    Article  PubMed  Google Scholar 

  100. Ludwig SC, Boden SD. Osteoinductive bone graft substitutes for spinal fusion: a basic science summary. Orthop Clin North Am 1999; 30:635–645.

    Article  CAS  PubMed  Google Scholar 

  101. Salgado AJ, Coutinho OP, Reis RL. Bone tissue engineering: State of the art and future trends. Macromol Biosci 2004; 4:743–765.

    Article  CAS  PubMed  Google Scholar 

  102. Pneumaticos SG, Triantafyllopoulos GK, Chatziioannou S et al. Biomolecular strategies of bone augmentation in spinal surgery. Trends Mol Med 2011; 17:215–222.

    Article  CAS  PubMed  Google Scholar 

  103. Oikarinen J, Korhonen LK. The bone inductive capacity of various bone transplanting materials used for treatment of experimental bone defects. Clin Orthop Relat Res 1979; 208–215.

    Google Scholar 

  104. Goldstein SA. Tissue engineering: functional assessment and clinical outcome. Ann N Y Acad Sci 2002; 961:183–192.

    Article  CAS  PubMed  Google Scholar 

  105. Grauer JN, Beiner JM, Kwon BK et al. Bone graft alternatives for spinal fusion. BioDrugs 2003; 17:391–394.

    Article  PubMed  Google Scholar 

  106. Devescovi V, Leonardi E, Ciapetti G et al. Growth factors in bone repair. Chir Organi Mov 2008; 92:161–168.

    Article  PubMed  Google Scholar 

  107. Takaoka K, Koezuka M, Nakahara H. Telopeptide-depleted bovine skin collagen as a carrier for bone morphogenetic protein. J Orthop Res 1991; 9:902–907.

    Article  CAS  PubMed  Google Scholar 

  108. Miyamoto S, Takaoka K, Okada T et al. Polylactic acid-polyethylene glycol block copolymer. A new biodegradable synthetic carrier for bone morphogenetic protein. Clin Orthop Relat Res 1993; 333–343.

    Article  Google Scholar 

  109. Patel ZS, Young S, Tabata Y et al. Dual delivery of an angiogenic and an osteogenic growth factor for bone regeneration in a critical size defect model. Bone 2008; 43:931–940.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Shah NJ, Macdonald ML, Beben YM et al. Tunable dual growth factor delivery from polyelectrolyte multilayer films. Biomaterials 2011; 32:6183–6193.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Wojtowicz AM, Shekaran A, Oest ME et al. Coating of biomaterial scaffolds with the collagen-mimetic peptide GFOGER for bone defect repair. Biomaterials 2010; 31:2574–2582.

    Article  CAS  PubMed  Google Scholar 

  112. Nguyen LH, Kudva AK, Saxena NS et al. Engineering articular cartilage with spatially-varying matrix composition and mechanical properties from a single stem cell population using a multi-layered hydrogel. Biomaterials 2011; 32:6946–6952.

    Article  CAS  PubMed  Google Scholar 

  113. Nguyen LH, Kudva AK, Guckert NL et al. Unique biomaterial compositions direct bone marrow stem cells into specific chondrocytic phenotypes corresponding to the various zones of articular cartilage. Biomaterials 2011; 32:1327–1338.

    Article  CAS  PubMed  Google Scholar 

  114. Behring J, Junker R, Walboomers XF et al. Toward guided tissue and bone regeneration: morphology, attachment, proliferation and migration of cells cultured on collagen barrier membranes. A systematic review. Odontology 2008; 96:1–11.

    Article  CAS  PubMed  Google Scholar 

  115. Delecrin J, Takahashi S, Gouin F et al. A synthetic porous ceramic as a bone graft substitute in the surgical management of scoliosis: a prospective, randomized study. Spine (Phila Pa 1976) 2000; 25:563–569.

    Article  CAS  Google Scholar 

  116. Gazdag AR, Lane JM, Glaser D et al. Alternatives to Autogenous Bone Graft: Efficacy and Indications. J Am Acad Orthop Surg 1995; 3:1–8.

    Article  CAS  PubMed  Google Scholar 

  117. Agrawal CM, Ray RB. Biodegradable polymeric scaffolds for musculoskeletal tissue engineering. J Biomed Mater Res 2001; 55:141–150.

    Article  CAS  PubMed  Google Scholar 

  118. Cordonnier T, Sohier J, Rosset P et al. Biomimetic materials for bone tissue engineering-state of the art and future trends. Adv Biomater (Weinheim, Ger) 2011; B135–B150.

    Article  CAS  Google Scholar 

  119. Drury JL, Mooney DJ. Hydrogels for tissue engineering: Scaffold design variables and applications. Biomaterials 2003; 24:4337–4351.

    Article  CAS  PubMed  Google Scholar 

  120. Burdick JA, Anseth KS. Photoencapsulation of osteoblasts in injectable RGD-modified PEG hydrogels for bone tissue engineering. Biomaterials 2002; 23:4315–4323.

    Article  CAS  PubMed  Google Scholar 

  121. Rosa AL, de Oliveira PT Beloti MM. Macroporous scaffolds associated with cells to construct a hybrid biomaterial for bone tissue engineering. Expert Rev Med Devices 2008; 5:719–728.

    Article  PubMed  Google Scholar 

  122. Oliveira AL, Reis RL. Pre-mineralization of starch/polycrapolactone bone tissue engineering scaffolds by a calcium-silicate-based process. J Mater Sci Mater Med 2004; 15:533–540.

    Article  CAS  PubMed  Google Scholar 

  123. Cancedda R, Dozin B, Giannoni P et al. Tissue engineering and cell therapy of cartilage and bone. Matrix Biol 2003; 22:81–91.

    Article  CAS  PubMed  Google Scholar 

  124. Vacanti CA, Kim W, Upton J et al. The efficacy of periosteal cells compared to chondrocytes in the tissue engineered repair of bone defects. Tissue Eng 1995; 1:301–308.

    Article  CAS  PubMed  Google Scholar 

  125. Kawaguchi J, Mee PJ, Smith AG. Osteogenic and chondrogenic differentiation of embryonic stem cells in response to specific growth factors. Bone 2005; 36:758–769.

    Article  CAS  PubMed  Google Scholar 

  126. Karp JM, Ferreira LS, Khademhosseini A et al. Cultivation of human embryonic stem cells without the embryoid body step enhances osteogenesis in vitro. Stem Cells 2006; 24:835–843.

    Article  PubMed  Google Scholar 

  127. Tian XF, Heng BC, Ge Z et al. Comparison of osteogenesis of human embryonic stem cells within 2D and 3D culture systems. Scand J Clin Lab Invest 2008; 68:58–67.

    Article  CAS  PubMed  Google Scholar 

  128. Seong JM, Kim BC, Park JH et al. Stem cells in bone tissue engineering. Biomed Mater 2010; 5:062001

    Article  PubMed  CAS  Google Scholar 

  129. Janicki P, Schmidmaier G. What should be the characteristics of the ideal bone graft substitute? Combining scaffolds with growth factors and/or stem cells. Injury 2011; 42 (Suppl 2):S77–81.

    Article  PubMed  Google Scholar 

  130. Yoshikawa T, Ohgushi H, Tamai S. Immediate bone forming capability of prefabricated osteogenic hydroxyapatite. J Biomed Mater Res 1996; 32:481–492.

    Article  CAS  PubMed  Google Scholar 

  131. Yamagiwa H, Endo N, Tokunaga K et al. In vivo bone-forming capacity of human bone marrow-derived stromal cells is stimulated by recombinant human bone morphogenetic protein-2. J Bone Miner Metab 2001; 19:20–28.

    Article  CAS  PubMed  Google Scholar 

  132. Costa-Pinto AR, Correlo VM, Sol PC et al. Osteogenic differentiation of human bone marrow mesenchymal stem cells seeded on melt based chitosan scaffolds for bone tissue engineering applications. Biomacromolecules 2009; 10:2067–2073.

    Article  CAS  PubMed  Google Scholar 

  133. Yu H, VandeVord PJ, Mao L et al. Improved tissue-engineered bone regeneration by endothelial cell mediated vascularization. Biomaterials 2009; 30:508–517.

    Article  CAS  PubMed  Google Scholar 

  134. Zhou J, Lin H, Fang T et al. The repair of large segmental bone defects in the rabbit with vascularized tissue engineered bone. Biomaterials 2010; 31:1171–1179.

    Article  CAS  PubMed  Google Scholar 

  135. Villars F, Bordenave L, Bareille R et al. Effect of human endothelial cells on human bone marrow stromal cell phenotype: role of VEGF? J Cell Biochem 2000; 79:672–685.

    Article  CAS  PubMed  Google Scholar 

  136. Shiozawa Y, Havens AM, Pienta KJ et al. The bone marrow niche: habitat to hematopoietic and mesenchymal stem cells and unwitting host to molecular parasites. Leukemia 2008; 22, 941–950.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res 1961; 25:585–621.

    Article  CAS  PubMed  Google Scholar 

  138. Nakagawa S, Gemmell NJ, Burke T. Measuring vertebrate telomeres: applications and limitations. Mol Ecol 2004; 13:2523–2533.

    Article  CAS  PubMed  Google Scholar 

  139. Muraglia A, Cancedda R, Quarto R. Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model. J Cell Sci 2000; 113 (Pt 7):1161–1166.

    CAS  PubMed  Google Scholar 

  140. Bodnar AG, Ouellette M, Frolkis M et al. Extension of life-span by introduction of telomerase into normal human cells. Science 1998; 279:349–352.

    Article  CAS  PubMed  Google Scholar 

  141. Shi S, Gronthos S, Chen S et al. Bone formation by human postnatal bone marrow stromal stem cells is enhanced by telomerase expression. Nat Biotechnol 2002; 20:587–591.

    Article  CAS  PubMed  Google Scholar 

  142. Simonsen JL, Rosada C, Serakinci N et al. Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells. Nat Biotechnol 2002; 20:592–596.

    Article  CAS  PubMed  Google Scholar 

  143. Gronthos S, Chen S, Wang CY et al. Telomerase accelerates osteogenesis of bone marrow stromal stem cells by upregulation of CBFA1, osterix and osteocalcin. J Bone Miner Res 2003; 18:716–722.

    Article  CAS  PubMed  Google Scholar 

  144. Zou D, Han W, You S et al. In vitro study of enhanced osteogenesis induced by HIF-1alpha-transduced bone marrow stem cells. Cell Prolif 2011; 44:234–243.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Zou D, Zhang Z, Ye D et al. Repair of critical-sized rat calvarial defects using genetically engineered bone marrow-derived mesenchymal stem cells overexpressing hypoxia-inducible factor-1alpha. Stem Cells 2011; 29:1380–1390.

    CAS  PubMed  Google Scholar 

  146. Walsh MC, Kim N, Kadono Y et al. Osteoimmunology: interplay between the immune system and bone metabolism. Annu Rev Immunol 2006; 24:33–63.

    Article  CAS  PubMed  Google Scholar 

  147. Deschaseaux F, Sensebe L, Heymann D. Mechanisms of bone repair and regeneration. Trends Mol Med 2009; 15:417–429.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Neurosurgery, City of Hope Cancer Center, Los Angeles, California, USA

    Lonnissa H. Nguyen, Vincent Duenas, Mike Y. Chen & Rahul Jandial

Authors
  1. Lonnissa H. Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vincent Duenas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mike Y. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rahul Jandial
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Neurosurgery, City of Hope Cancer Center and Beckman Research Institute, Los Angeles, California, USA

    Rahul Jandial MD, PhD  & Mike Y. Chen MD, PhD  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Nguyen, L.H., Duenas, V., Chen, M.Y., Jandial, R. (2012). Progenitor Cells: Role and Usage in Bone Tissue Engineering Approaches for Spinal Fusion. In: Jandial, R., Chen, M.Y. (eds) Regenerative Biology of the Spine and Spinal Cord. Advances in Experimental Medicine and Biology, vol 760. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4090-1_12

Download citation

Publish with us

Policies and ethics

Search

Navigation