J Korean Soc Spine Surg.  2001 Sep;8(3):372-377. 10.4184/jkss.2001.8.3.372.

Growth Factors and Their Clinical Applications

• Moon SH
• Kim HS
• Lee HM

• KMID: 2209759
• DOI: http://doi.org/10.4184/jkss.2001.8.3.372

Abstract

Growth factor is a polypeptide regulating cell proliferation, maturation, activity, and apoptosis. Despite its small molecular weight, it exerts diverse and potent biologic effects on cellular function. With recent development of molecular biology and vector technology, it is now possible to administer recombinant growth factors in clinical dose and modify somatic cell with growth factor encoding gene. Research fields in spinal surgery can be divided into spinal fusion, disc regeneration and spinal cord regeneration. In this review, we discuss the action mechanism of growth factors and their possible clinical applications especially in the field of spinal fusion and disc regeneration.

Keyword

Growth factor; Spinal fusion; Disc degeneration

MeSH Terms

Apoptosis
Cell Proliferation
Fibrinogen
Intercellular Signaling Peptides and Proteins*
Intervertebral Disc Degeneration
Molecular Biology
Molecular Weight
Regeneration
Spinal Cord Regeneration
Spinal Fusion
Fibrinogen
Intercellular Signaling Peptides and Proteins

Reference

1). Boden SD, Zdeblick TA, Sandhu HS, Heim SE. The use of rhBMP-2 in interbody fusion cages. Definitive evidence of osteoinduction in humans: a preliminary report. Spine. 25(3):376–81. 2000.

2). Grauer JN, Patel TC, Erulkar JS, Troiano NW, Panjabi MM, Friedlaender GE. Evaluation of OP-1 as a graft substitute for intertransverse process lumbar fusion. Spine. 26(2):127–33. 2000.

3). Grimsrud CD, Romano PR, D'Souza M, Puzas JE, Sch-warz EM, Reynolds PR, Roiser RN, O'Keefe RJ. BMP signaling stimulates chondrocyte maturation and the expression of Indian hedgehog. J Orthop Res. 19(1):18–25. 2001.

4). Gruber HE, Fisher EC Jr, Desai B, Stasky AA, Hoelscher G, Hanley EN Jr. Human intervertebral disc cells from the annulus: three-dimensional culture in agarose or alginate and responsiveness to TGF-beta1. Exp Cell Res. 235(1):13–21. 1997.

5). Gruber HE, Norton HJ, Hanley EN Jr. Anti-apop -totic effects of IGF-1 and PDGF on human intervertebral disc cells in vitro. Spine. 25(17):2153–7. 2000.

6). Hanada K, Solchaga LA, Caplan AI, Hering TM, Goldberg VM, Yoo JU, Johnstone B. BMP-2 induction and TGF-beta1 modulation of rat periosteal cell chondro -genesis. J Cell Biochem. 81(2):284–94. 2001.

7). Hanahan D, Weinberg RA. The Hallmarks of Cancer. Cell. 100:57–70. 2000.

8). 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. 92(2 Suppl):191–6. 2000.

9). Hunter T. Signalling-2000 and beyond. Cell. 100:113–127. 2000.

10). Itoh S, Itoh F, Goumans M-J, Dijke PT. Signalling of transforming growth factor-ß family members through Smad protein. Eur J Biochem. 267:6954–6967. 2000.

11). Jeppsson C, Saveland H, Rydholm U, Aspenberg P. OP-1 for cervical spine fusion: bridging bone in only 1 of 4 rheumatoid patients but prednisolone did not inhibit bone induction in rats. Acta Orthop Scand. 70(6):559–63. 1999.

12). Laursen M, Hoy K, Hansen ES, Gelineck J, Christensen FB, Bunger CE. Recombinant bone morphogenetic protein-7 as an intracorporal bone growth stimulator in unstable thoracolumbar burst fractures in humans: preliminary results. Eur Spine J. 8(6):485–90. 1999.

13). Levi-Montalcini R. The nerve growth factor 35 years later. Science. 237:1154–1162. 1987.

14). Lowery GL, Kulkarni S, Pennisi AE. Use of autolo - gous growth factors in lumbar spinal fusion. Bone. 25(2 Suppl):47S–50S. 1999.

15). Magin MN, Delling G. Improved lumbar vertebral interbody fusion using rhOP-1: a comparison of autogenous bone graft, bovine hydroxylapatite(Bio-Oss), and BMP-7 (rhOP-1) in sheep. Spine. 26(5):469–78. 2001.

16). Moon SH, Gilbertson LG, Nishida K, Knaub MA, Muz-zonigro T, Robbins PD, Evans CH, Kang JD. Human interverterbal disc cells are genetically modifiable by adenovirus-mediated gene transfer. Spine. 25:2573–79. 2000.

17). Moon SH, Kang JD, Nishida K, Gilbertson LG, Niyibizi C, Smith PN, Knaub MA, Robbins PD, Evans CH. Human cervical intervertebral disc cells are susceptible to adenovirus-mediated gene therapy -Therapeutic gene transfer-. Proceedings of 27th annual meeting, Cervical Spine Research Society, p150-153. 1999.

18). Moon SH, Lee HM, Park MS, Kim H, Kang ES, Kim HS, Gilbertson LG, Kang JD. BMP-2 upregulate the mRNA expression of aggrecan, collagen type I, collagen type II in human interverterbal disc cells. Orthopaedic Research Society. 2002. (Submitted).

19). Moon SH, Nishida K, Gilbertson LG, Hall RA, Robbins PD, Kang JD. Biologic response of human interverterbal disc cells to gene therapy cocktail. Proceedings of Orthopaedic Research Society. 2000.

20). Moon SH, Nishida K, Gilbertson LG, Knaub MA, Smith PN, Robbins PD, Evans CH, Kang JD. Proteog lycan synthesis in human intervertebral disc cells cultured in alginate beads: Exogenous TGF-beta1 vs. adenovirus-mediated gene transfer of TGF-beta1 cDNA. Proceedings of Orthopaedic Research Society. 2000.

21). Monroe MA, Boden SD, Hair G, Martin GJ Jr, Racine M, Titus L, Hutton WC. Gene expression during autograft lumbar spine fusion and the effect of bone morphogenetic protein 2. Clin Orthop. 351:252–65. 1998.

22). Muschik M, Schlenzka D, Ritsila V, Tennstedt C, Lewandrowski KU. Experimental anterior spine fusion using bovine bone morphogenetic protein: a study in rabbits. J Orthop Sci. 5(2):165–70. 2000.

23). Muschler GF, Hyodo A, Manning T, Kambic H, Easley K. Evaluation of human bone morphogenetic protein 2 in a canine spinal fusion model. Clin Orthop. 308:229–40. 1994.

24). Nishida K, Kang JD, Suh J-K, Robbins PD, Evans CH, Gilbertson LG. Adenovirus-mediated gene transfer to nucleus pulposus cells: Implication for the treatment of intervertebral disc degeneration. Spine. 23:2437–2443. 1998.

25). Nishida K, Kang JD, Gilbertson LG, Moon S-H, Suh J-K, Vogt MT, Robbins PD, Evans CH. Modulation of the biologic activity of the rabbit intervertebral disc by gene therapy: An in vivo study of adenovirus-mediated transfer of the human transforming growth factor ß 1 encoding gene. Spine. 24:2419–2425. 1999.

26). Osada R, Ohshima H, Ishihara H, Yudoh K, Sakai K, Matsui H, Tsuji H. Autocrine/paracrine mechanism of insulin-like growth factor-1 secretion, and the effect of insulin-like growth factor-1 on proteoglycan synthesis in bovine intervertebral discs. J Orthop Res. 14(5):690–9. 1996.

27). 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. 63(4):357–60. 1998.

28). Sandhu HS. Anterior lumbar interbody fusion with osteoinductive growth factors. Clin Orthop. 371:56–60. 2000.

29). Schimandle JH, Boden SD, Hutton WC. Exp eri -mental spinal fusion with recombinant human bone morphogenetic protein-2. Spine. 20(12):1326–37. 1995.

30). Smith P, Shuler FD, Georgescu HI, Ghivizzani SC, Johnstone B, Niyibizi C, Robbins PD, Evans CH. Gene tic enhancement of matrix synthesis by articular chondrocytes: comparison of different growth factor genes in the presence and absence of interleukin-1. Arthritis Rheum. 43(5):1156–64. 2000.

31). Solheim E. Osteoinduction by demineralised bone. Int Orthop. 22(5):335–42. 1998.

32). Thompson JP, Oegema TR Jr, Bradford DS. Stimulation of mature canine intervertebral disc by growth factors. Spine. 16(3):253–60. 1991.

33). Viggeswarapu M, Boden SD, Liu Y, Hair GA, Lois-Ugbo J, Murakami H, Kim H-S, 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. 83(A):364–376. 2001.