Bone substitution in spine fusion: The past, the present, and the future

Minimally Invasive Surgery of the Lumbar Spine

Volumn , Issue , 2014, Pages 311-331

  Logroscino, Giandomenico ^a   Lattanzi, Wanda ^a  

^a UNIVERSITÀ CATTOLICA DEL SACRO CUORE   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84918770752     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-4471-5280-4     Document Type: Chapter

References (134)

1. Etminan M, Girardi FP, Khan SN, et al. Revision strategies for lumbar pseudarthrosis. Orthop Clin North Am. 2002;33:381-92.
2. Boden SD. Overview of the biology of lumbar spine fusion and principles for selecting a bone graft substitute. Spine (Phila Pa 1976). 2002;27(16 Suppl 1):S26-31.
3. Cowan JA, Dimick JB, Wainess R, Upchurch GR, Chandler WF, La Marca F. Changes in the utilization of spinal fusion in the United States. Neurosurgery. 2006;59:15-20.
4. Reid JJ, Johnson JS, Wang JC. Challenges to bone formation in spinal fusion. J Biomech. 2011;44(2):213-20.
5. Giannoudis PV, Einhorn TA, Marsh D. Fracture healing: the diamond concept. Injury. 2007;38 Suppl 4:S3-6.
6. Axhausen G. Arch k1in Chir. 1909;88:23-28.
7. Phemister DB. Surg Gynecol Obstet. 1914;19:303-307.
8. Barth A. Die entstehung und das wachstum der freien gelenkkorper. Eine histologischklinische studie. Arch f Klin Chir. 1898;56:507-73.
9. Wigfield CC, Nelson RJ. Nonautologous interbody fusion materials in cervical spine surgery: how strong is the evidence to justify their use? Spine. 2001;26:687-94.
10. Rawlinson JN. Morbidity after anterior cervical decompression and fusion. The influence of the donor site on recovery, and the results of a trial of surgibone compared to autologous bone. Acta Neurochir (Wien). 1994;131:106-18.
11. Khan SN, Cammisa Jr FP, Sandhu HS, Diwan AD, Girardi FP, Lane JM. The biology of bone grafting. J Am Acad Orthop Surg. 2005;13(1):77-86.
12. Tomford WW. Transmission of disease through transplantation of musculoskeletal allografts. J Bone Joint Surg Am. 1995;77:1742-54.
13. Laurencin CT, El-Amin SF. Xenotransplantation in orthopaedic surgery. J Am Acad Orthop Surg. 2008;16(1):4-8.
14. Maatz R, Bauermeister A. A method of bone maceration. Results of animal experiments. J Bone Joint Surg Am. 1957;39:153-66.
15. Lofgren H, Johannsson V, Olsson T, Ryd L, Levander B. Rigid fusion after cloward operation for cervical disc disease using autograft, allograft, or xenograft: a randomized study with radiostereometric and clinical follow-up assessment. Spine. 2000;25:1908-16.
16. Malca SA, Roche PH, Rosset E, Pellet W. Cervical interbody xenograft with plate fixation: evaluation of fusion after 7 years of use in post-traumatic discoligamentous instability. Spine. 1996;21:685-90.
17. Ramani PS, Kalbag RM, Sengupta RP. Cervical spinal interbody fusion with Kiel bone. Br J Surg. 1975;62:147-50.
18. Savolainen S, Usenius JP, Hernesniemi J. Iliac crest versus artificial bone grafts in 250 cervical fusions. Acta Neurochir (Wien). 1994;129:54-7.
19. Siqueira EB, Kranzler LI. Cervical interbody fusion using calf bone. Surg Neurol. 1982;18:37-9.
20. Beer M, Charalambides C, Cobb AG. Poor results after augmenting autograft with xenograft (surgibone) in hip revision surgery: a report of 27 cases. Acta Orthop. 2005;76(4):544-9.
21. Lerner T, Bullmann V, Schulte TL, Schneider M, Liljenqvist U. A level-1 pilot study to evaluate of ultraporous beta-tricalcium phosphate as a graft extender in the posterior correction of adolescent idiopathic scoliosis. Eur Spine J. 2009;18(2):170-9.
22. Boyan BD, McMillan J, Lohmann CH, Ranly DM, Schwartz Z. Bone graft substitutes: basic information for successful clinical use with special focus on synthetic graft substitutes. In: Laurencin CT, editor. Bone graft substitutes. West Conshohocken: ASTM International; 2003. p. 231-59.
23. Yamamuro T, Shikata J, Okumura H, et al. Replacement of lumbar vertebrae of sheep with ceramic prostheses. J Bone Joint Surg Br. 1990;72:889-93.
24. Dai L, Jiang L. Anterior cervical fusion with interbody cage containing beta-tricalcium phosphate augmented with plate fixation: a prospective randomized study with 2-year follow-up. Eur Spine J. 2008;17:698-705.
25. Kim P, Wakai S, Matsuo S, Moriyama T, Kirino T. Bisegmental cervical interbody fusion using hydroxyapatite implants: surgical results and long-term observation in 70 cases. J Neurosurg. 1998;88:21-7.
26. Suetsuna F, Yokoyama T, Kenuka E, Harata S. Anterior cervical fusion using porous hydroxyapatite ceramics for cervical disc herniation. A two-year follow-up. Spine J. 2001;1:348-57.
27. Lowenstam HA, Weiner S. On biomineralization. New York: Oxford University Press; 1989.
28. Le Geros RZ. Calcium phosphates in oral biology and medicine. In: Myers KH, editor. Monographs in oral science, vol. 15. Basel: AG Publishers; 1991. p. 82-107.
29. Korovessis P, Repantis T, Petsinis G, Iliopoulos P, Hadjipavlou A. Direct reduction of thoracolumbar burst fractures by means of balloon kyphoplasty with calcium phosphate and stabilization with pedicle-screw instrumentation and fusion. Spine (Phila Pa 1976). 2008;33(4):E100-8.
30. Bigi A, Foresti E, Gregoriani R, Ripamonti A, Roveri N, Shah JS. The role of magnesium on the structure of biological apatite. Calcif Tissue Int. 1992;50:439-44.
31. Bigi A, Falini G, Foresti E, Gazzano M, Ripamonti A, Roveri N. Magnesium influence on hydroxyapatite crystallization. J Inorg Biochem. 1993;49:69-78.
32. TenHuisen KS, Brown PW. Effects of magnesium on the formation of calcium deficient hydroxyapatite from CaHPO4 · 2H2O and Ca4(PO4)2O. J Biomed Mater Res. 1997;36:306-14.
33. Rey C, Renugopalakrishnan V, Collins B, Glimcher M. Fourier transform infrared spectroscopic study of the carbonate ions in bone mineral during aging. Calcif Tissue Int. 1991;49:251-8.
34. Landi E, Tampieri A, Mattioli-Belmonte M, Celotti G. Biomimetic Mg- and Mg, CO3- substituted hydroxyapatites: synthesis characterization and in vitro behaviour. J Eur Ceramic Soc. 2006;26:2593-601.
35. Landi E, Logroscino G, Proietti L, Tampieri A, Sandri M, Sprio S. Biomimetic Mg-substituted hydroxyapatite: from synthesis to in vivo behaviour. J Mater Sci Mater Med. 2008;19:239-47.
36. Hillmeier J, et al.Augmentation von Wirbelkorperfrakturen mit einem neuen CalciumphosphateZement nach Ballon-Kphoplastie. Orthopade. 2004;33(1):31-9.
37. Maestretti G, Cremer C, Otten P, Jakob RP. Prospective study of standalone balloon kypho- plasty with calcium phosphate cement augmentation in traumatic fractures. Eur Spine J. 2007;16(5):601-10.
38. Verlaan JJ, Oner FC, Slootweg PJ, Verbout AJ, Dhert WJ. Histologic changes after vertebroplasty. J Bone Joint Surg Am. 2004;86:1230-8.
39. Chow LC, Takagi S, Constantino PD. Self-setting calcium phosphate cements. Mat Res Soc Symp Proc. 1991;179:1-24.
40. Driessens FC, Planell JA, Gil FJ. Calcium phosphate bone cements. In: Wise DL et al., editors. Encyclopedic handbook of biomaterials and bioengineering part B, applications, vol. 2. New York: Marcel Dekker; 1995. p. 855-77.
41. Toyone T, Tanaka T, Kato D, Kaneyama R, Otsuka M. The treatment of acute thoracolumbar burst fractures with transpedicular intracorporeal hydroxyapatite grafting following indirect reduction and pedicle screw fixation: a prospective study. Spine. 2006;31:E208-14.
42. Lim TH, Brebach GT, Renner SM, Kim WJ, Kim JG, Lee RE, et al. Biomechanical evaluation of an injectable calcium phosphate treatment of acute thoracolumbar burst fractures with kyphoplasty an intracorporeal grafting with calcium phosphate: a prospective study. Spine. 2002;27:1297-302.
43. Tomita S, Molloy S, Jasper LE, Abe M, Belkoff SM. Biomechanical comparison of kypho- plasty with different bone cements. Spine. 2004;29:1203-7.
44. Cho DY, Lee WY, Sheu PC. Treatment of thoracolumbar burst fractures with polymethyl methacrylate vertebroplasty and short segment pedicle screw fixation. Neurosurgery. 2003;53:1354-61.
45. Gelb H, Schumacher HR, Cuckler J, Ducheyne P, Baker DG. In vivo inflammatory response to polymethylmethacrylate particulate debris: effect of size, morphology and surface area. J Orthop Res. 1994;12:83-92.
46. San Millân Ruiz D, Burkhardt K, Jean B, Muster M, Martin JB, Bouvier J, et al. Pathology findings with acrylic implants. Bone. 1999;25:85S-90.
47. Bai B, Jazrawi LM, Kummer FJ, Spivak JM. The use of an injectable, biodegradable calcium phosphate bone substitute for the prophylactic augmentation of osteoporotic vertebrae and the management of vertebral compression fractures. Spine. 1999;24: 1521-6.
48. Dujovny M, Aviles A, Agner C. An innovative approach for cranioplasty using hydroxyapatite cement. Surg Neurol. 1997;48:294-7.
49. LeGeros RZ. Properties of osteoconductive biomaterials: calcium phosphates. Clin Orthop Relat Res. 2002;395:81-98.
50. Ooms EM, Wolke JG, van der Waerden JP, Jansen JA. Trabecular bone response to injectable calcium phosphate (Ca-P) cement. J Biomed Mater Res. 2002;61:9-18.
51. Verlaan JJ, van Helden WH, Oner FC, Verbout AJ, Dhert WJ. Balloon vertebroplasty with calcium phosphate cement augmentation for direct restoration of traumatic thoracolumbar vertebral fractures. Spine. 2002;27:543-8.
52. Korovessis P, Repantis T, George P. Treatment of acute thoracolumbar burst fractures with kyphoplasty and short pedicle screw fixation: transpedicular intracorporeal grafting with calcium phosphate: a prospective study. Indian J Orthop. 2007;41(4):354-61.
53. Blattert TR, Jestaedt L, Weckbach A. Suitability of a calcium phosphate cement in osteoporotic vertebral body fracture augmentation: a controlled, randomized, clinical trial of balloon kyphoplasty comparing calcium phosphate versus polymethylmethacrylate. Spine (Phila Pa 1976). 2009;34(2):108-14.
54. Yoon ST, Boden SD. Spine fusion by gene therapy. Gene Ther. 2004;11(4):360-7.
55. Baltzer AW, Lieberman JR. Regional gene therapy to enhance bone repair. Gene Ther. 2004;11(4):344-50.
56. Pneumaticos SG, Triantafyllopoulos GK, Chatziioannou S, Basdra EK, Papavassiliou AG. Biomolecular strategies of bone augmentation in spinal surgery. Trends Mol Med. 2011;17(4):215-22.
57. Lattanzi W, Pola E, Pecorini G, Logroscino CA, Robbins PD. Gene therapy for in vivo bone formation: recent advances. Eur Rev Med Pharmacol Sci. 2005;9(3):167-74.
58. Lattanzi W, Parrilla C, Fetoni A, Logroscino G, Straface G, Pecorini G, Stigliano E, Tampieri A, Bedini R, Pecci R, Michetti F, Gambotto A, Robbins PD, Pola E. Ex vivo-transduced autologous skin fibroblasts expressing human Lim mineralization protein-3 efficiently form new bone in animal models. Gene Ther. 2008;15(19):1330-43. PubMed PMID: 18633445.
59. Parrilla C, Saulnier N, Bernardini C, Patti R, Tartaglione T, Fetoni AR, Pola E, Paludetti G, Michetti F, Lattanzi W. Undifferentiated human adipose tissue-derived stromal cells induce mandibular bone healing in rats. Arch Otolaryngol Head Neck Surg. 2011;137(5):463-70.
60. Gomez-Barrena E, Rosset P, Müller I, Giordano R, Bunu C, Layrolle P, Konttinen YT, Luyten FP. Bone regeneration: stem cell therapies and clinical studies in orthopaedics and traumatology. J Cell Mol Med. 2011;15(6):1266-86.
61. Horwitz EM, Le Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I, Marini FC, Deans RJ, Krause DS, Keating A, International Society for Cellular Therapy. Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy. 2005;7(5):393-5.
62. 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(5411):143-7.
63. De Bari C, Dell’Accio F, Tylzanowski P, Luyten FP. Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum. 2001;44(8):1928-42.
64. Asakura A, Komaki M, Rudnicki M. Muscle satellite cells are multipotential stem cells that exhibit myogenic, osteogenic, and adipogenic differentiation. Differentiation. 2001;68(4-5):245-53.
65. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7(2):211-28.
66. Erices A, Conget P, Minguell JJ. Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol. 2000;109(1):235-42.
67. Saulnier N, Lattanzi W, Puglisi MA, Pani G, Barba M, Piscaglia AC, Giachelia M, Alfieri S, Neri G, Gasbarrini G, Gasbarrini A. Mesenchymal stromal cells multipotency and plasticity: induction toward the hepatic lineage. Eur Rev Med Pharmacol Sci. 2009;13 Suppl 1:71-8.
68. Prockop DJ, Oh JY. Medical therapies with adult stem/progenitor cells (MSCs): a backward journey from dramatic results in vivo to the cellular and molecular explanations. J Cell Biochem. 2012;113(5):1460-9.
69. Prockop DJ, Kota DJ, Bazhanov N, Reger RL. Evolving paradigms for repair of tissues by adult stem/progenitor cells (MSCs). J Cell Mol Med. 2010;14(9):2190-9.
70. Horwitz EM, Gordon PL, Koo WK, Marx JC, Neel MD, McNall RY, Muul L, Hofmann T. Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone. Proc Natl Acad Sci USA. 2002;99(13):8932-7.
71. Chamberlain JR, Schwarze U, Wang PR, Hirata RK, Hankenson KD, Pace JM, Underwood RA, Song KM, Sussman M, Byers PH, Russell DW. Gene targeting in stem cells from individuals with osteogenesis imperfecta. Science. 2004;303(5661):1198-201.
72. Huang JW, Lin SS, Chen LH, Liu SJ, Niu CC, Yuan LJ, Wu CC, Chen WJ. The use of fluorescence-labeled mesenchymal stem cells in poly(lactide-co-glycolide)/hydroxyapatite/collagen hybrid graft as a bone substitute for posterolateral spinal fusion. J Trauma. 2011;70(6):1495-502.
73. Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008;8(9):726-36.
74. Zaim M, Karaman S, Cetin G, Isik S. Donor age and long-term culture affect differentiation and proliferation of human bone marrow mesenchymal stem cells. Ann Hematol. 2012;91(8):1175-86.
75. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13(12):4279-95.
76. Katz AJ, Tholpady A, Tholpady SS, Shang H, Ogle RC. Cell surface and transcriptional characterization of human adipose-derived adherent stromal (hADAS) cells. Stem Cells. 2005;23(3):412-23.
77. Saulnier N, Puglisi MA, Lattanzi W, Castellini L, Pani G, Leone G, Alfieri S, Michetti F, Piscaglia AC, Gasbarrini A. Gene profiling of bone marrow- and adipose tissue-derived stromal cells: a key role of Kruppel-like factor 4 in cell fate regulation. Cytotherapy. 2011;13(3):329-40.
78. Gimble JM, Bunnell BA, Chiu ES, Guilak F. Concise review: adipose-derived stromal vascular fraction cells and stem cells: let’s not get lost in translation. Stem Cells. 2011;29(5):749-54.
79. Riew KD, Wright NM, Cheng S, Avioli LV, Lou J. Induction of bone formation using a recombinant adenoviral vector carrying the human BMP-2 gene in a rabbit spinal fusion model. Calcif Tissue Int. 1998;63(4):357-60.
80. Cheng SL, Lou J, Wright NM, Lai CF, Avioli LV, Riew KD. In vitro and in vivo induction of bone formation using a recombinant adenoviral vector carrying the human BMP-2 gene. Calcif Tissue Int. 2001;68(2):87-94.
81. Cui Q, Ming Xiao Z, Balian G, Wang GJ. Comparison of lumbar spine fusion using mixed and cloned marrow cells. Spine (Phila Pa 1976). 2001;26(21):2305-10.
82. Hidaka C, Goshi K, Rawlins B, Boachie-Adjei O, Crystal RG. Enhancement of spine fusion using combined gene therapy and tissue engineering BMP-7-expressing bone marrow cells and allograft bone. Spine (Phila Pa 1976). 2003;28(18):2049-57.
83. Orii H, Sotome S, Chen J, Wang J, Shinomiya K. Beta-tricalcium phosphate (beta-TCP) graft combined with bone marrow stromal cells (MSCs) for posterolateral spine fusion. J Med Dent Sci. 2005;52(1):51-7.
84. Kruyt MC, Wilson CE, de Bruijn JD, van Blitterswijk CA, Oner CF, Verbout AJ, Dhert WJ. The effect of cell-based bone tissue engineering in a goat transverse process model. Biomaterials. 2006;27(29):5099-106.
85. Miyazaki M, Sugiyama O, Tow B, Zou J, Morishita Y, Wei F, Napoli A, Sintuu C, Lieberman JR, Wang JC. The effects of lentiviral gene therapy with bone morphogenetic protein-2-producing bone marrow cells on spinal fusion in rats. J Spinal Disord Tech. 2008;21(5):372-9.
86. Miyazaki M, Sugiyama O, Zou J, Yoon SH, Wei F, Morishita Y, Sintuu C, Virk MS, Lieberman JR, Wang JC. Comparison of lentiviral and adenoviral gene therapy for spinal fusion in rats. Spine (Phila Pa 1976). 2008;33(13):1410-7.
87. Kim HJ, Park JB, Lee JK, Park EY, Park EA, Riew KD, Rhee SK. Transplanted xenogenic bone marrow stem cells survive and generate new bone formation in the posterolateral lumbar spine of non-immunosuppressed rabbits. Eur Spine J. 2008;17(11):1515-21.
88. Fu TS, Chen WJ, Chen LH, Lin SS, Liu SJ, Ueng SW. Enhancement of posterolateral lumbar spine fusion using low-dose rhBMP-2 and cultured marrow stromal cells. J Orthop Res. 2009;27(3):380-4.
89. Rao RD, Gourab K, Bagaria VB, Shidham VB, Metkar U, Cooley BC. The effect of platelet- rich plasma and bone marrow on murine posterolateral lumbar spine arthrodesis with bone morphogenetic protein. J Bone Joint Surg Am. 2009;91(5):1199-206.
90. Fu TS, Ueng SW, Tsai TT, Chen LH, Lin SS, Chen WJ. Effect of hyperbaric oxygen on mesenchymal stem cells for lumbar fusion in vivo. BMC Musculoskelet Disord. 2010;11:52.
91. Giannicola G, Ferrari E, Citro G, Sacchetti B, Corsi A, Riminucci M, Cinotti G, Bianco P. Graft vascularization is a critical rate-limiting step in skeletal stem cell-mediated posterolateral spinal fusion. J Tissue Eng Regen Med. 2010;4(4):273-83.
92. Geuze RE, Prins HJ, Öner FC, van der Helm YJ, Schuijff LS, Martens AC, Kruyt MC, Alblas J, Dhert WJ. Luciferase labeling for multipotent stromal cell tracking in spinal fusion versus ectopic bone tissue engineering in mice and rats. Tissue Eng Part A. 2010;16(11):3343-51.
93. Douglas JT, Rivera AA, Lyons GR, Lott PF, Wang D, Zayzafoon M, Siegal GP, Cao X, Theiss SM. Ex vivo transfer of the Hoxc-8-interacting domain of Smad1 by a tropism-modified adenoviral vector results in efficient bone formation in a rabbit model of spinal fusion. J Spinal Disord Tech. 2010;23(1):63-73.
94. Johnson JS, Meliton V, Kim WK, Lee KB, Wang JC, Nguyen K, Yoo D, Jung ME, Atti E, Tetradis S, Pereira RC, Magyar C, Nargizyan T, Hahn TJ, Farouz F, Thies S, Parhami F. Novel oxysterols have pro-osteogenic and anti-adipogenic effects in vitro and induce spinal fusion in vivo. J Cell Biochem. 2011;112(6):1673-84.
95. Abbah SA, Lam CX, Ramruttun AK, Goh JC, Wong HK. Fusion performance of low-dose recombinant human bone morphogenetic protein 2 and bone marrow-derived multipotent stromal cells in biodegradable scaffolds: a comparative study in a large animal model of anterior lumbar interbody fusion. Spine (Phila Pa 1976). 2011;36(21):1752-9.
96. Hsu WK, Wang JC, Liu NQ, Krenek L, Zuk PA, Hedrick MH, Benhaim P, Lieberman JR. Stem cells from human fat as cellular delivery vehicles in an athymic rat posterolateral spine fusion model. J Bone Joint Surg Am. 2008;90(5):1043-52.
97. Sheyn D, Pelled G, Zilberman Y, Talasazan F, Frank JM, Gazit D, Gazit Z. Nonvirally engineered porcine adipose tissue-derived stem cells: use in posterior spinal fusion. Stem Cells. 2008;26(4):1056-64.
98. Lopez MJ, McIntosh KR, Spencer ND, Borneman JN, Horswell R, Anderson P, Yu G, Gaschen L, Gimble JM. Acceleration of spinal fusion using syngeneic and allogeneic adult adipose derived stem cells in a rat model. J Orthop Res. 2009;27(3):366-73.
99. McIntosh KR, Lopez MJ, Borneman JN, Spencer ND, Anderson PA, Gimble JM. Immunogenicity of allogeneic adipose-derived stem cells in a rat spinal fusion model. Tissue Eng Part A. 2009;15(9):2677-86.
100. Vergroesen PP, Kroeze RJ, Helder MN, Smit TH. The use of poly(L-lactide-co-caprolactone) as a scaffold for adipose stem cells in bone tissue engineering: application in a spinal fusion model. Macromol Biosci. 2011;11(6):722-30.
101. Tang ZB, Cao JK, Wen N, Wang HB, Zhang ZW, Liu ZQ, Zhou J, Duan CM, Cui FZ, Wang CY. Posterolateral spinal fusion with nano-hydroxyapatite-collagen/PLA composite and autologous adipose-derived mesenchymal stem cells in a rabbit model. J Tissue Eng Regen Med. 2012;6(4):325-36.
102. Miyazaki M, Zuk PA, Zou J, Yoon SH, Wei F, Morishita Y, Sintuu C, Wang JC. Comparison of human mesenchymal stem cells derived from adipose tissue and bone marrow for ex vivo gene therapy in rat spinal fusion model. Spine (Phila Pa 1976). 2008;33(8):863-9.
103. Gimble JM, Bunnell BA, Chiu ES, Guilak F. Taking stem cells beyond discovery: a milestone in the reporting of regulatory requirements for cell therapy. Stem Cells Dev. 2011;20(8):1295-6.
104. Olabisi RM, Lazard Z, Heggeness MH, Moran KM, Hipp JA, Dewan AK, Davis AR, West JL, Olmsted-Davis EA. An injectable method for noninvasive spine fusion. Spine J. 2011;11(6):545-56.
105. Parrilla C, Lattanzi W, Rita Fetoni A, Bussu F, Pola E, Paludetti G. Ex vivo gene therapy using autologous dermal fibroblasts expressing hLMP3 for rat mandibular bone regeneration. Head Neck. 2010;32(3):310-8.
106. Lattanzi W, Bernardini C. Genes and molecular pathways of the osteogenic process. In: Yunfeng Lin, editor. Osteogenesis. InTech; 2012. ISBN:978-953-51-0030-0. Available from: http://www. intechopen.com/books/osteogenesis/genes-and-molecular-pathways-of-the-osteogenic-process.
107. Miyazono K, Maeda S, Imamura T. BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev. 2005;16(3):251-63.
108. Wu X, Shi W, Cao X. Multiplicity of BMP signaling in skeletal development. Ann N Y Acad Sci. 2007;1116:29-49.
109. Katagiri T, Yamaguchi A, Komaki M, Abe E, Takahashi N, Ikeda T, Rosen V, Wozney JM, Fujisawa-Sehara A, Suda T. Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. J Cell Biol. 1994;127(6 Pt 1):1755-66.
110. Okamoto M, Murai J, Yoshikawa H, Tsumaki N. Bone morphogenetic proteins in bone stimulate osteoclasts and osteoblasts during bone development. J Bone Miner Res. 2006;21(7):1022-33.
111. Pham L, Beyer K, Jensen ED, Rodriguez JS, Davydova J, Yamamoto M, Petryk A, Gopalakrishnan R, Mansky KC. Bone morphogenetic protein 2 signaling in osteoclasts is negatively regulated by the BMP antagonist, twisted gastrulation. J Cell Biochem. 2011;112(3):793-803.
112. Bahamonde ME, Lyons KM. BMP3: to be or not to be a BMP. J Bone Joint Surg Am. 2001;83-A(Suppl 1(Pt 1)):S56-62.
113. Balint E, Lapointe D, Drissi H, van der Meijden C, Young DW, van Wijnen AJ, Stein JL, Stein GS, Lian JB. Phenotype discovery by gene expression profiling: mapping of biological processes linked to BMP-2-mediated osteoblast differentiation. J Cell Biochem. 2003;89(2):401-26.
114. Canalis E, Economides AN, Gazzerro E. Bone morphogenetic proteins, their antagonists, and the skeleton. Endocr Rev. 2003;24(2):218-35.
115. Evans C. Gene therapy for the regeneration of bone. Injury. 2011;42(6):599-604.
116. Hwang CJ, Vaccaro AR, Lawrence JP, Hong J, Schellekens H, Alaoui-Ismaili MH, Falb D. Immunogenicity of bone morphogenetic proteins. J Neurosurg Spine. 2009;10(5):443-51.
117. Alaoui-Ismaili MH, Falb D. Design of second generation therapeutic recombinant bone morphogenetic proteins. Cytokine Growth Factor Rev. 2009;20(5-6):501-7.
118. Alden TD, Pittman DD, Beres EJ, Hankins GR, Kallmes DF, Wisotsky BM, Kerns KM, Helm GA. Percutaneous spinal fusion using bone morphogenetic protein-2 gene therapy. J Neurosurg. 1999;90(1 Suppl):109-14.
119. Zhao J, Zhao DY, Shen AG, Liu F, Zhang F, Sun Y, Wu HF, Lu CF, Shi HG. Promoting lumbar spinal fusion by adenovirus-mediated bone morphogenetic protein-4 gene therapy. Chin J Traumatol. 2007;10(2):72-6.
120. Laurent JJ, Webb KM, Beres EJ, McGee K, Li J, van Rietbergen B, Helm GA. The use of bone morphogenetic protein-6 gene therapy for percutaneous spinal fusion in rabbits. J Neurosurg Spine. 2004;1(1):90-4.
121. Helm GA, Alden TD, Beres EJ, Hudson SB, Das S, Engh JA, Pittman DD, Kerns KM, Kallmes DF. Use of bone morphogenetic protein-9 gene therapy to induce spinal arthrodesis in the rodent. J Neurosurg. 2000;92(2 Suppl):191-6.
122. Sheyn D, Kallai I, Tawackoli W, Cohn Yakubovich D, Oh A, Su S, Da X, Lavi A, Kimelman- Bleich N, Zilberman Y, Li N, Bae H, Gazit Z, Pelled G, Gazit D. Gene-modified adult stem cells regenerate vertebral bone defect in a rat model. Mol Pharm. 2011;8(5):1592-601.
123. Lu SS, Zhang X, Soo C, Hsu T, Napoli A, Aghaloo T, Wu BM, Tsou P, Ting K, Wang JC. The osteoinductive properties of nell-1 in a rat spinal fusion model. Spine J. 2007;7(1):50-60.
124. Kim HS, Viggeswarapu M, Boden SD, Liu Y, Hair GA, Louis-Ugbo J, Murakami H, Minamide A, Suh DY, Titus L. Overcoming the immune response to permit ex vivo gene therapy for spine fusion with human type 5 adenoviral delivery of the LIM mineralization protein-1 cDNA. Spine (Phila Pa 1976). 2003;28(3):219-26.
125. Ting K, Vastardis H, Mulliken JB, Soo C, Tieu A, Do H, Kwong E, Bertolami CN, Kawamoto H, Kuroda S, Longaker MT. Human NELL-1 expressed in unilateral coronal synostosis. J Bone Miner Res. 1999;14(1):80-9.
126. Aghaloo T, Cowan CM, Chou YF, Zhang X, Lee H, Miao S, Hong N, Kuroda S, Wu B, Ting K, Soo C. Nell-1-induced bone regeneration in calvarial defects. Am J Pathol. 2006;169(3):903-15.
127. Boden SD, Titus L, Hair G, Liu Y, Viggeswarapu M, Nanes MS, Baranowski C. Lumbar spine fusion by local gene therapy with a cDNA encoding a novel osteoinductive protein (LMP-1). Spine (Phila Pa 1976). 1998;23(23):2486-92.
128. Bernardini C, Saulnier N, Parrilla C, Pola E, Gambotto A, Michetti F, Robbins PD, Lattanzi W. Early transcriptional events during osteogenic differentiation of human bone marrow stromal cells induced by Lim mineralization protein 3. Gene Expr. 2010;15(1):27-42.
129. Minamide A, Boden SD, Viggeswarapu M, Hair GA, Oliver C, Titus L. Mechanism of bone formation with gene transfer of the cDNA encoding for the intracellular protein LMP-1. J Bone Joint Surg Am. 2003;85-A(6):1030-9.
130. Strohbach CA, Rundle CH, Wergedal JE, Chen ST, Linkhart TA, Lau KH, Strong DD. LMP-1 retroviral gene therapy influences osteoblast differentiation and fracture repair: a preliminary study. Calcif Tissue Int. 2008;83(3):202-11. PubMed PMID: 18709396.
131. Wang X, Cui F, Madhu V, Dighe AS, Balian G, Cui Q. Combined VEGF and LMP-1 delivery enhances osteoprogenitor cell differentiation and ectopic bone formation. Growth Factors. 2011;29(1):36-48. PubMed PMID: 21222516.
132. Yoon ST, Park JS, Kim KS, Li J, Attallah-Wasif ES, Hutton WC, Boden SD. ISSLS prize winner: LMP-1 upregulates intervertebral disc cell production of proteoglycans and BMPs in vitro and in vivo. Spine (Phila Pa 1976). 2004;29(23):2603-11. PubMed PMID: 15564908.
133. Viggeswarapu M, Boden SD, Liu Y, Hair GA, Louis-Ugbo J, Murakami H, Kim HS, Mayr MT, Hutton WC, Titus L. Adenoviral delivery of LIM mineralization protein-1 induces new- bone formation in vitro and in vivo. J Bone Joint Surg Am. 2001;83-A(3):364-76. PubMed PMID: 11263640.
134. Lattanzi W, Barba M, Novegno F, Massimi L, Tesori V, Tamburrini G, Galgano S, Bernardini C, Caldarelli M, Michetti F, Di Rocco C. Lim mineralization protein is involved in the premature calvarial ossification in sporadic craniosynostoses. Bone. 2013;52(1):474-84. doi:10.1016/j.bone.2012.09.004.