Skip to main content

Advertisement

SpringerLink
Log in

Lumbar intervertebral disc allograft transplantation: the revascularisation pattern

  • Original Article
  • Published:
European Spine Journal Aims and scope Submit manuscript

Abstract

Purpose

Fresh frozen intervertebral disc allograft transplantation has been reported to be a viable treatment option for advanced degenerative disc diseases, but rapid degeneration of the postoperative allograft was found. Loss of nutrient supply is believed to be the most likely inducer because the disc allografts have to endure in an ischaemic environment until the nutrient pathway is re-established. The aim of this study was to focus on the revascularisation of the disc allograft after transplantation in goats.

Methods

Twenty male goats were used in this study. Intervertebral disc allograft transplantation was performed at L4/L5. Groups of five goats were killed at 1.5, 6 and 12 m postoperatively, respectively. The transplanted segments were harvested, fixed, sagittally cut and decalcified for H&E staining and immunochemistry to observe the blood vessel formation at the endplates, anterior outer annulus, posterior outer annulus, inner annulus and the nucleus. The blood vessel density and the sectional vessel area were measured.

Results

Blood vessels were first found in the marrow space of the bony endplate and the outer annulus at 1.5 month postoperatively. Then, they were able to penetrate to reach the cartilaginous endplate and the inner annulus after 6 months. Interestingly, the endplate area possessed the most abundant blood vessels, with the highest level of vessel density and area at the final follow-up. None of these newly formed vessels invaded the nucleus during the observation period.

Conclusions

Revascularisation of the postoperative disc allograft has been determined, but its pattern was different from that in adult normal discs, suggesting that the typical nutrient diffusion pattern may be affected after transplantation.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Silvestre JS, Smadja DM, Levy BI (2013) Postischemic revascularization: from cellular and molecular mechanisms to clinical applications. Physiol Rev 93:1743–1802. https://doi.org/10.1152/physrev.00006.201393/4/1743

    Article  CAS  PubMed  Google Scholar 

  2. Bhama JK, Nguyen DQ, Scolieri S, Teuteberg JJ, Toyoda Y, Kormos RL, McCurry KR, McNamara D, Bermudez CA (2009) Surgical revascularization for cardiac allograft vasculopathy: is it still an option? J Thorac Cardiovasc Surg 137:1488–1492. https://doi.org/10.1016/j.jtcvs.2009.02.026

    Article  PubMed  Google Scholar 

  3. Wingenfeld C, Egli RJ, Hempfing A, Ganz R, Leunig M (2002) Cryopreservation of osteochondral allografts: dimethyl sulfoxide promotes angiogenesis and immune tolerance in mice. J Bone Joint Surg Am 84-A:1420–1429

    Article  PubMed  Google Scholar 

  4. Xue C, Zhang L, Shuang F, Zhang Y, Luo D, Kang X, Wang X, Hou S, Zhong H (2013) Robust revascularization, despite impaired VEGF production, after meniscus allograft transplantation in rabbits. Am J Sports Med 41:2668–2675. https://doi.org/10.1177/0363546513499139

    Article  PubMed  Google Scholar 

  5. Stevenson S, Emery SE, Goldberg VM (1996) Factors affecting bone graft incorporation. Clin Orthop Relat Res 324:66–74

    Article  Google Scholar 

  6. Delloye C, Cornu O, Druez V, Barbier O (2007) Bone allografts: what they can offer and what they cannot. J Bone Joint Surg Br 89:574–579. https://doi.org/10.1302/0301-620X.89B5.19039

    Article  CAS  PubMed  Google Scholar 

  7. Willems WF, Larsen M, Giusti G, Friedrich PF, Bishop AT (2011) Revascularization and bone remodeling of frozen allografts stimulated by intramedullary sustained delivery of FGF-2 and VEGF. J Orthop Res 29:1431–1436. https://doi.org/10.1002/jor.21338

    Article  CAS  PubMed  Google Scholar 

  8. Huang C, Tang M, Yehling E, Zhang X (2014) Overexpressing sonic hedgehog peptide restores periosteal bone formation in a murine bone allograft transplantation model. Mol Ther 22:430–439. https://doi.org/10.1038/mt.2013.222

    Article  CAS  PubMed  Google Scholar 

  9. Nachemson A, Lewin T, Maroudas A, Freeman MA (1970) In vitro diffusion of dye through the end-plates and the annulus fibrosus of human lumbar inter-vertebral discs. Acta Orthop Scand 41:589–607

    Article  CAS  PubMed  Google Scholar 

  10. Huang YC, Urban JP, Luk KD (2014) Intervertebral disc regeneration: do nutrients lead the way? Nat Rev Rheumatol 10:561–566. https://doi.org/10.1038/nrrheum.2014.91

    Article  PubMed  Google Scholar 

  11. Roberts S, Menage J, Urban JP (1989) Biochemical and structural properties of the cartilage end-plate and its relation to the intervertebral disc. Spine (Phila Pa 1976) 14:166–174

    Article  CAS  Google Scholar 

  12. Luk KD, Ruan DK, Chow DH, Leong JC (1997) Intervertebral disc autografting in a bipedal animal model. Clin Orthop Relat Res 337:13–26

    Article  Google Scholar 

  13. Luk KD, Ruan DK, Lu DS, Fei ZQ (2003) Fresh frozen intervertebral disc allografting in a bipedal animal model. Spine (Phila Pa 1976) 28:864–869. https://doi.org/10.1097/01.BRS.0000058710.01729.29 (discussion 870)

    Google Scholar 

  14. Luk KD, Ruan DK (2008) Intervertebral disc transplantation: a biological approach to motion preservation. Eur Spine J 17(Suppl 4):504–510. https://doi.org/10.1007/s00586-008-0748-0

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ruan D, He Q, Ding Y, Hou L, Li J, Luk KD (2007) Intervertebral disc transplantation in the treatment of degenerative spine disease: a preliminary study. Lancet 369:993–999. https://doi.org/10.1016/S0140-6736(07)60496-6

    Article  PubMed  Google Scholar 

  16. Ding Y, Ruan DK, He Q, Hou LS, Lin JN, Cui HP (2016) Imaging evaluation and relative significance in cases of cervical disc allografting: radiographic character following total disc transplantation. Clin Spine Surg. https://doi.org/10.1097/BSD.0b013e318290fc41

    Google Scholar 

  17. Xiao J, Huang YC, Lam SK, Luk KD (2015) Surgical technique for lumbar intervertebral disc transplantation in a goat model. Eur Spine J 24:1951–1958. https://doi.org/10.1007/s00586-014-3631-1

    Article  PubMed  Google Scholar 

  18. Melero-Martin JM, Khan ZA, Picard A, Wu X, Paruchuri S, Bischoff J (2007) In vivo vasculogenic potential of human blood-derived endothelial progenitor cells. Blood 109:4761–4768. https://doi.org/10.1182/blood-2006-12-062471

    Article  CAS  PubMed  Google Scholar 

  19. Lee CH, Cook JL, Mendelson A, Moioli EK, Yao H, Mao JJ (2010) Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study. Lancet 376:440–448. https://doi.org/10.1016/S0140-6736(10)60668-X

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kloeters O, Berger I, Ryssel H, Megerle K, Leimer U, Germann G (2011) Revitalization of cortical bone allograft by application of vascularized scaffolds seeded with osteogenic induced adipose tissue derived stem cells in a rabbit model. Arch Orthop Trauma Surg 131:1459–1466. https://doi.org/10.1007/s00402-011-1306-5

    Article  PubMed  Google Scholar 

  21. Huang YC, Xiao J, Leung WY, Lu WW, Hu Y, Luk KD (2016) Lumbar intervertebral disc allograft transplantation: healing and remodelling of the bony structure. Eur Cell Mater 32:216–227. https://doi.org/10.22203/eCM.v032a14

    Article  Google Scholar 

  22. Chen W, Liu J, Manuchehrabadi N, Weir MD, Zhu Z, Xu HH (2013) Umbilical cord and bone marrow mesenchymal stem cell seeding on macroporous calcium phosphate for bone regeneration in rat cranial defects. Biomaterials 34:9917–9925. https://doi.org/10.1016/j.biomaterials.2013.09.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Cackowski FC, Anderson JL, Patrene KD, Choksi RJ, Shapiro SD, Windle JJ, Blair HC, Roodman GD (2010) Osteoclasts are important for bone angiogenesis. Blood 115:140–149. https://doi.org/10.1182/blood-2009-08-237628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Huang YC, Xiao J, Lu WW, Leung VYL, Hu Y, Luk KDK (2017) Lumbar intervertebral disc allograft transplantation: long-term mobility and impact on the adjacent segments. Eur Spine J 26:799–805. https://doi.org/10.1007/s00586-016-4535-z

    Article  PubMed  Google Scholar 

  25. Urban JP, Smith S, Fairbank JC (2004) Nutrition of the intervertebral disc. Spine (Phila Pa 1976) 29:2700–2709

    Article  Google Scholar 

  26. Kobayashi S, Baba H, Takeno K, Miyazaki T, Uchida K, Kokubo Y, Nomura E, Morita C, Yoshizawa H, Meir A (2008) Fine structure of cartilage canal and vascular buds in the rabbit vertebral endplate. Laboratory investigation. J Neurosurg Spine 9:96–103. https://doi.org/10.3171/SPI/2008/9/7/096

    Article  PubMed  Google Scholar 

  27. Nerlich AG, Schaaf R, Walchli B, Boos N (2007) Temporo-spatial distribution of blood vessels in human lumbar intervertebral discs. Eur Spine J 16:547–555. https://doi.org/10.1007/s00586-006-0213-x

    Article  PubMed  Google Scholar 

  28. Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9:669–676. https://doi.org/10.1038/nm0603-669

    Article  CAS  PubMed  Google Scholar 

  29. Fujita N, Imai J, Suzuki T, Yamada M, Ninomiya K, Miyamoto K, Iwasaki R, Morioka H, Matsumoto M, Chiba K, Watanabe S, Suda T, Toyama Y, Miyamoto T (2008) Vascular endothelial growth factor-a is a survival factor for nucleus pulposus cells in the intervertebral disc. Biochem Biophys Res Commun 372:367–372. https://doi.org/10.1016/j.bbrc.2008.05.044

    Article  CAS  PubMed  Google Scholar 

  30. Binch AL, Cole AA, Breakwell LM, Michael AL, Chiverton N, Cross AK, Le Maitre CL (2014) Expression and regulation of neurotrophic and angiogenic factors during human intervertebral disc degeneration. Arthritis Res Ther 16:416. https://doi.org/10.1186/s13075-014-0416-1

    Article  PubMed  Google Scholar 

  31. Chan SC, Lam S, Leung VY, Chan D, Luk KD, Cheung KM (2010) Minimizing cryopreservation-induced loss of disc cell activity for storage of whole intervertebral discs. Eur Cell Mater 19:273–283

    Article  CAS  PubMed  Google Scholar 

  32. Lam SK, Chan SC, Leung VY, Lu WW, Cheung KM, Luk KD (2011) The role of cryopreservation in the biomechanical properties of the intervertebral disc. Eur Cell Mater 22:393–402

    Article  CAS  PubMed  Google Scholar 

  33. Schuerwegh AJ, Dombrecht EJ, Stevens WJ, Van Offel JF, Bridts CH, De Clerck LS (2003) Influence of pro-inflammatory (IL-1 alpha, IL-6, TNF-alpha, IFN-gamma) and anti-inflammatory (IL-4) cytokines on chondrocyte function. Osteoarthr Cartil 11:681–687

    Article  CAS  PubMed  Google Scholar 

  34. John T, Kohl B, Mobasheri A, Ertel W, Shakibaei M (2007) Interleukin-18 induces apoptosis in human articular chondrocytes. Histol Histopathol 22:469–482

    CAS  PubMed  Google Scholar 

  35. Podichetty VK (2007) The aging spine: the role of inflammatory mediators in intervertebral disc degeneration. Cell Mol Biol (Noisy-le-grand) 53:4–18

    CAS  Google Scholar 

  36. Alini M, Eisenstein SM, Ito K, Little C, Kettler AA, Masuda K, Melrose J, Ralphs J, Stokes I, Wilke HJ (2008) Are animal models useful for studying human disc disorders/degeneration? Eur Spine J 17:2–19. https://doi.org/10.1007/s00586-007-0414-y

    Article  PubMed  Google Scholar 

  37. Kauppila LI (2009) Atherosclerosis and disc degeneration/low-back pain—a systematic review. Eur J Vasc Endovasc Surg 37:661–670. https://doi.org/10.1016/j.ejvs.2009.02.006

    Article  CAS  PubMed  Google Scholar 

  38. Grunhagen T, Shirazi-Adl A, Fairbank JC, Urban JP (2011) Intervertebral disk nutrition: a review of factors influencing concentrations of nutrients and metabolites. Orthop Clin North Am 42:465–477, vii. https://doi.org/10.1016/j.ocl.2011.07.010

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We are very grateful to Mr. Jun-Ling Zeng from Nanfang Hospital, Guangzhou, and Prof. Li Deng and Mrs. Xiu-Qun Li from Sichuan University, Chengdu, China, for kind support in this study. This work was financially supported by the Research Grants Council of Hong Kong (773112), the Tam Sai Kit Endowment Fund and the National Natural Science Foundation of China (81702171).

Author information

Author notes

  1. Yong-Can Huang and Jun Xiao contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopaedics and Traumatology, The University of Hong Kong, 5/F Professor Block, Queen Mary Hospital, Pokfulam, Hong Kong SAR, China

    Yong-Can Huang, Victor Y. Leung, William W. Lu, Yong Hu & Keith D. K. Luk

  2. Shenzhen Engineering Laboratory of Orthopaedic Regenerative Technologies, Orthopaedic Research Center, Peking University Shenzhen Hospital, Shenzhen, China

    Yong-Can Huang

  3. Department of Joint Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China

    Jun Xiao

Authors
  1. Yong-Can Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jun Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Victor Y. Leung
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. William W. Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yong Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Keith D. K. Luk
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Keith D. K. Luk.

Ethics declarations

Conflict of interest

The authors report no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, YC., Xiao, J., Leung, V.Y. et al. Lumbar intervertebral disc allograft transplantation: the revascularisation pattern. Eur Spine J 27, 728–736 (2018). https://doi.org/10.1007/s00586-017-5419-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00586-017-5419-6

Keywords

Search

Navigation