Adipose-derived stem cells enhance primary tendon repair: Biomechanical and immunohistochemical evaluation☆

https://doi.org/10.1016/j.bjps.2012.06.011Get rights and content

Summary

Background

Primary tendon repair aims at increased tensile strength at the time of mobilisation. Tendon repair and regeneration using mesenchymal stem cells have been described in different studies; however, adipose-derived stem cell (ASC) use for tendon regeneration and repair has recently been taken into consideration. In this study, we sought to determine whether ASCs would be beneficial in primary tendon healing.

Materials and methods

Both the Achilles tendons of rabbits (n = 6) were incised and consequently repaired. To the left side was applied platelet-rich plasma (PRP) gel and to the right side autologous ASC-mixed PRP. The tensile strength was measured on the 4th week. The samples were taken for immunohistochemical evaluation of collagen type I, transforming growth factor beta (TGF-β) 1, 2, 3, fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF).

Results

The tensile strengths in control and experimental groups were found out to be 29.46 ± 3.66 and 43.06 ± 3.80 kgf. Collagen type I, FGF and VEGF levels were statistically higher, whereas TGF-β1, 2, 3 were lower in the experimental group.

Conclusion

ASCs enhance primary tendon healing; however, the complex interaction and the cascades by which ASCs could increase collagen type I, FGF and VEGF and decrease TGF-β levels should further be investigated.

Section snippets

Isolation and preparation of ASCs

Ten-week-old white Japanese rabbits (Saitama Experimental Animals Supply Corporation Ltd., Saitama, Japan) were anaesthetised with sodium pentobarbital (Nembutal; Dainippon Sumitomo Pharma Co. Ltd., Osaka, Japan) at 35 mg kg−1 and shaved. ASCs were harvested and processed according to our established protocol.16, 17, 18 The inguinal fat pads were excised and extensively washed with phosphate-buffered saline (PBS) (Gibco-BRL, Grand Island, NY, USA). They were then finely minced, and incubated on

Biomechanical evaluation

The non-operated Achilles tendon tensile strength was confirmed in the preliminary study as 55–60 kgf. The tendons at the 4th week were exposed (Figure 2). The tensile strength in the control and the experimental group were found out to be 29.46 ± 3.66 kgf and 43.06 ± 3.80 kgf, respectively. There was a statistical difference between the groups (p < 0.05) (Figure 3).

Histological examination

The alignment of collagen bundles in the control group was irregular; however, in the experimental group it was partially regular

Discussion

Primary tendon repair aims increased tensile strength at the time of mobilisation. This would enable early mobilisation and thus improve the range of motion of the joint. Different types of repair techniques and the suture materials have been investigated.2, 21, 22, 23, 24, 25 Various authors have described suture techniques to increase the strength of the repair.26, 27 As a result, Tajima's modification of the Kessler repair remains widely used despite the fact that it may not be as strong as

Ethical approval

The authors state that they complied with the ‘standards of animal care’ and the ethical permission number (from Nippon Medical School Ethical Committee) was given in the Materials and methods part.

Conflict of interest

The authors state that there are not any conflicts of interest or funding about the study.

References (57)

  • H.A. Eriksen et al.

    Increased content of type III collagen at the rupture site of human Achilles tendon

    J Orthop Res

    (2002)
  • J.B. Tang et al.

    Expression of genes for collagen production and NF-kappaB gene activation of in vivo healing flexor tendons

    J Hand Surg [Am]

    (2004)
  • A.Y. Zhang et al.

    Inhibition of TGF-beta-induced collagen production in rabbit flexor tendons

    J Hand Surg [Am]

    (2004)
  • J. Chang et al.

    Molecular studies in flexor tendon wound healing: the role of basic fibroblast growth factor gene expression

    J Hand Surg [Am]

    (1998)
  • C. Hsu et al.

    Clinical implications of growth factors in flexor tendon wound healing

    J Hand Surg [Am]

    (2004)
  • R.E. Marx

    Platelet-rich plasma: evidence to support its use

    J Oral Maxillofac Surg

    (2004)
  • P. Harrison et al.

    Platelet alpha-granules

    Blood Rev

    (1993)
  • G. Weibrich et al.

    Growth factor levels in platelet-rich plasma and correlations with donor age, sex, and platelet count

    J Craniomaxillofac Surg

    (2002)
  • C. Frank et al.

    Collagen fibril diameters in the rabbit medial collateral ligament scar: a longer term assessment

    Connect Tissue Res

    (1997)
  • M. Lehfeldt et al.

    MOC-PS(SM) CME article: treatment of flexor tendon laceration

    Plast Reconstr Surg

    (Apr 2008)
  • M. Ngo et al.

    Differential expression of transforming growth factor-beta receptors in a rabbit zone II flexor tendon wound healing model

    Plast Reconstr Surg

    (Oct 2001)
  • J. Folkman et al.

    Angiogenic factors

    Science

    (1987)
  • W.A. Border et al.

    Transforming growth factor-β in disease: the dark side of tissue repair

    J Clin Invest

    (1992)
  • J. Chang et al.

    Studies in flexor tendon wound healing: neutralizing antibody to TGF-beta1 increases postoperative range of motion

    Plast Reconstr Surg

    (Jan 2000)
  • G.C. Gurtner et al.

    Progress and potential for regenerative medicine

    Annu Rev Med

    (2007)
  • H.A. Awad et al.

    Autologous mesenchymal stem cell-mediated repair of tendon

    Tissue Eng

    (1999)
  • R.G. Young et al.

    Use of mesenchymal stem cells in a collagen matrix for Achilles tendon repair

    J Orthop Res

    (1998)
  • N. Juncosa-Melvin et al.

    The effect of autologous mesenchymal stem cells on the biomechanics and histology of gel-collagen sponge constructs used for rabbit patellar tendon repair

    Tissue Eng

    (2006)

    • Cited by (143)

    • Morphological, histological and biomechanical comparison of bone marrow aspirate concentrate, micro-fragmented adipose tissue and platelet-rich plasma in prevention of tendon adhesion

      2023, Journal of Plastic, Reconstructive and Aesthetic Surgery

    • Biomechanical comparison of different suture materials with different techniques in tendon repair: An ex-vivo study

      2023, Hand Surgery and Rehabilitation

    • Regenerative Medicine and Rehabilitation Therapy in the Canine

      2023, Veterinary Clinics of North America - Small Animal Practice

    • Adipose-derived stem cells: Use in clinical medicine

      2023, Principles of Gender-Specific Medicine: Sex and Gender-Specific Biology in the Postgenomic Era

    • Therapies related to mesenchymal stem cells for cartilage, joint, and bone diseases

      2023, Joint and Bone: From Bench to Bedside

    • New, biomechanically sound tendon tissue after injection of uncultured, autologous, adipose derived regenerative cells in partial Achilles tendon defects in rabbits

      2024, bioRxiv
    View all citing articles on Scopus
    ☆

    Meetings at which this study was presented:

    1) 6th Annual Meeting of the International Federation of Adipose Therapeutics and Science (IFATS), 24–26 October, 2008, Toulouse, France.

    2) 54th Annual Meeting of Plastic Surgery Research Council, 27–30 May, 2009, Pittsburg, USA.

    View full text
    Copyright © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.