Skip to main content
Log in

ACL reconstruction in a rabbit model using irradiated Achilles allograft seeded with mesenchymal stem cells or PDGF-B gene-transfected mesenchymal stem cells

  • Knee
  • Published:
Knee Surgery, Sports Traumatology, Arthroscopy Aims and scope

Abstract

The present study was conducted to develop a new strategy to accelerate reconstruction of the anterior cruciate ligament (ACL) by modifying the Achilles allograft with autogenous mesenchymal stem cells (MSCs) or PDGF-B transfected MSCs in a rabbit model. The allografts were first irradiated with Co60, stored at −80°C, and then seeded with cells for implantation. Bilateral ACL reconstructions were performed. On the left, the allograft was either seeded with MSCs or PDGF-B transfected MSCs and acted as the experimental group. On the right, the graft without any cells seeded acted as control. At 3, 6 and 12 weeks after surgery, histological observation found that implatation of MSCs or PDGF-B transfected MSCs accelerated cellular infiltration into the ACL and enhanced collagen deposition in the wound. PDGF-B transfected MSCs could also lead to an initial promotion of angiogenesis. This gene transfer technique or cell implantion may be a potentially useful tool for improving ligament remodeling.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Arnoczky SP, Warren RF, Ashlock MA (1986) Replacement of the anterior cruciate ligament using a patellar tendon allograft: an experimental study. J Bone Joint Surg Am 68A:376–385

    Google Scholar 

  2. Awad HA, Butler DL, Boivin GP, Smith FN, Malaviya P, Huibregtse B, Caplan AI (1999) Autologous mesenchymal stem cell-mediated repair of tendon. Tissue Eng 5:267–277

    Article  PubMed  CAS  Google Scholar 

  3. Awad HA, Butler DL, Dressler MR, Smith F, Boivin GP, Young RG (2003) Repair of patellar tendon injuries using mesenchymal stem cells and collagen scaffolds. J Orthop Res 21:420–431

    Article  PubMed  CAS  Google Scholar 

  4. Batten ML, Hansen JC, Dahners LE (1996) Influence of dosage and timing of application of platelet-derived growth factor on early healing of the rat medial collateral ligament. J Orthop Res 14:736–741

    Article  PubMed  CAS  Google Scholar 

  5. Bellincampi LD, Closkey RF, Prasad R, Zawadsky JP, Dunn MG (1998) Viability of fibroblast-seeded ligament analogs after autogenous implantation. J Orthop Res 16:414–420

    Article  PubMed  CAS  Google Scholar 

  6. Bos GD, Goldberg VM, Powell AE, Heiple KG, Zika JM (1984) The effect of histocompatibility matching on canine frozen bone allografts. J Bone Joint Surg Am 65A:89–96

    Google Scholar 

  7. Heldin C-H, Westermark B (1999) Mechanism of action and in vivo role of Platelet-derived growth factor. Phys Rev 79:1283–1316

    CAS  Google Scholar 

  8. DesRosiers EA, Yahia L, Rivard CH (1996) Proliferative and matrix synthesis response of canine anterior cruciate ligament fibroblasts submitted to combined growth factors. J Orthop Res 14:200–208

    Article  PubMed  CAS  Google Scholar 

  9. Dunn MG, Liesch JB, Tiku ML, Zawadsky JP (1995) Development of fibroblast-seeded ligament analogs for ACL reconstruction. J Biomed Mater Res 29:1363–1371

    Article  PubMed  CAS  Google Scholar 

  10. Friedlaender GE, Strong DM, Sell KW (1976) Studies on the antigenicity of bone: freeze-dried and deep-frozen bone allografts in rabbits. J. Bone Joint Surg Am 58A:854–858

    Google Scholar 

  11. Graham WC, Smith PA, McGuire MP (1955) The use of frozen stored tendons for grafting: an experimental study. J Bone Joint Surg Am 37A:624

    Google Scholar 

  12. Hildebrand KA, Woo SL, Smith DW, Allen CR, Deie M, Taylor BJ, Schmidt CC (1998) The effects of platelet-derived growth factor-BB on healing of the rabbit medial collateral ligament: an in vivo study. Am J Sports Med 26:549–554

    PubMed  CAS  Google Scholar 

  13. Kang HJ, Kang ES (1999) Ideal concentration of growth factors in rabbit’s flexor tendon culture. Yonsei Med J 40:26–29

    PubMed  CAS  Google Scholar 

  14. Letson AK, Dahners LE (1994) The effect of combinations of growth factors on ligament healing. Clin Orthop Relat Res 308:207–212

    PubMed  Google Scholar 

  15. Lin VS, Lee MC, O’Neal S, McKean J, Sung KL (1999) Ligament tissue engineering using synthetic biodegradable fiber scaffolds. Tissue Eng 5:443–452

    Article  PubMed  CAS  Google Scholar 

  16. Meaney Murray M, Rice K, Wright RJ, Spector M (2003) The effect of selected growth factors on human anterior cruciate ligament cell interactions with a three-dimensional collagen–GAG scaffold. J Orthop Res 21:238–244

    Article  PubMed  CAS  Google Scholar 

  17. Minami A, Ishii S, Ogino T (1982) The effect of the immunological antigenicity of the allogenic tendinosus tendon grafting. Hand 14:111–119

    Article  PubMed  CAS  Google Scholar 

  18. Minguell JJ, Erices A, Conget P (2002) Mesenchymal stem cells. Exp Biol Med 226:507–520

    Google Scholar 

  19. Agung M, Ochi M, Yanada S, Adachi N, Izuta Y, Yamasaki T, Toda K (2006) Mobilization of bone marrow-derived mesenchymal stem cells into the injured tissues after intraarticular injection and their contribution to tissue regeneration. Knee Surg Sports Traumatol Arthrosc 14:1307–1314

    Article  PubMed  Google Scholar 

  20. Nakamura N, Shino K, Natsuume T, Horibe S, Matsumoto N, Kaneda Y, Ochi T (1998) Early biological effect of in vivo gene transfer of platelet-derived growth factor (PDGF)-B into healing patellar ligament. Gene Ther 5:1165–1170

    Article  PubMed  CAS  Google Scholar 

  21. Peacock EE, Petty J (1960) Antigenicity of tendon. J Surg Gynecol Obstet 110:187–192

    Google Scholar 

  22. Peter M, Prokopis, Schepsis AA (1999) Allograft use in ACL reconstruction. Knee 6:75–85

    Article  Google Scholar 

  23. Petersen W, Pufe T, Zantop T, Tillmann B, Mentlein R (2003) Hypoxia and PDGF have a synergistic effect that increases the expression of the angiogenetic peptide vascular endothelial growth factor in Achilles tendon fibroblasts. Arch Orthop Trauma Surg 123:485–488

    Article  PubMed  Google Scholar 

  24. Kuroda R, Kurosaka M, Yoshiya S, Mizuno K (2000) Localization of growth factors in the reconstructed anterior cruciate ligament: immunohistological study in dogs. Knee Surg Sports Traumatol Arthrosc 8:120–126

    Article  PubMed  CAS  Google Scholar 

  25. Scherping SC Jr, Schmidt CC, Georgescu HI, Kwoh CK, Evans CH, Woo SL (1997) Effect of growth factors on the proliferation of ligament fibroblasts from skeletally mature rabbits. Connect Tissue Res 36:1–8

    Article  PubMed  CAS  Google Scholar 

  26. Schmidt CC, Georgescu HI, Kwoh CK, Blomstrom GL, Engle CP, Larkin LA, Evans CH, Woo SL (1995) Effect of growth factors on the proliferation of fibroblasts from the medial collateral and anterior cruciate ligaments. J Orthop Res 13:184–190

    Article  PubMed  CAS  Google Scholar 

  27. Spindler KP, Clark SW, Nanney LB, Davidson JM (1996) Expression of collagen and matrix metalloproteinases in ruptured human anterior cruciate ligament: an in situ hybridization study. J Orthop Res 14:857–861

    Article  PubMed  CAS  Google Scholar 

  28. Stevenson S, Honn RB, Templeton JW (1983) Effects of tissue antigen matching on the healing of fresh cancellous bone allografts in dogs. Am J Vet Res 44:204–206

    Google Scholar 

  29. Van Ei jk F, Saris DB, Riesle J, Willems WJ, Van Blitterswi jk CA, Verbout AJ, Dhert WJ (2004) Tissue engineering of ligaments: a comparison of bone marrow stromal cells, anterior cruciate ligament, and skin fibroblast as cell source. Tissue Eng 10:893–903

    Article  CAS  Google Scholar 

  30. Wakitani S, Goto T, Pineda SJ, Young RG, Mansour JM, Caplan AI, Goldberg VM (1994) Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am 76:579–592

    PubMed  CAS  Google Scholar 

  31. Watanabe N, Woo SL, Papageorgiou C, Celechovsky C, Takai S (2002) Fate of donor bone marrow cells in medial collateral ligament after simulated autologous transplantation. Microsc Res Tech 58:39–44

    Article  PubMed  Google Scholar 

  32. Yasuhiro Y, Abrahamson S (2000) Dose-related effects of platelet-derived growth factor-BB vary by different rabbit tendons in vitro. Transactions of the 46th annual meeting of the Orthopaedic Research Society

  33. Young RG, Butler DL, Weber W, Caplan AI, Gordon SL, Fink DJ (1998) Use of mesenchymal stem cells in a collagen matrix for Achilles tendon repair. J Orthop Res 16:406–413

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Professor Carl-Henrik Heldin, Ludwig Institute for Cancer Research, Sweden and Christer Betsholtz, Institute of Medical Biochemistry, University of Gothenburg, Sweden for helping us in our study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Changlong Yu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, F., Jia, H. & Yu, C. ACL reconstruction in a rabbit model using irradiated Achilles allograft seeded with mesenchymal stem cells or PDGF-B gene-transfected mesenchymal stem cells. Knee Surg Sports Traumatol Arthr 15, 1219–1227 (2007). https://doi.org/10.1007/s00167-007-0385-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00167-007-0385-x

Keywords

Navigation