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Research Article| Volume 65, ISSUE 12, P1712-1719, December 2012

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

      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.

      Keywords

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      References

        • Frank C.
        • McDonald D.
        • Shrive N.
        Collagen fibril diameters in the rabbit medial collateral ligament scar: a longer term assessment.
        Connect Tissue Res. 1997; 36: 261
        • Lehfeldt M.
        • Ray E.
        • Sherman R.
        MOC-PS(SM) CME article: treatment of flexor tendon laceration.
        Plast Reconstr Surg. Apr 2008; 121: 1
        • Evans R.B.
        • Thompson D.E.
        The application of force to the healing tendon.
        J Hand Ther. Oct–Dec 1993; 6: 266
        • Duffy Jr., F.J.
        • Seiler J.G.
        • Gelberman R.H.
        • Hergrueter C.A.
        Growth factors and canine flexor tendon healing: initial studies in uninjured and repair models.
        J Hand Surg (Am). 1995; 20: 645
        • Ngo M.
        • Pham H.
        • Longaker M.T.
        • Chang J.
        Differential expression of transforming growth factor-beta receptors in a rabbit zone II flexor tendon wound healing model.
        Plast Reconstr Surg. Oct 2001; 108: 1260
        • Bennett N.T.
        • Schultz G.S.
        Growth factors and wound healing: biochemical properties of growth factors and their receptors.
        Am J Surg. 1993; 165: 728
        • Folkman J.
        • Klagsbrun M.
        Angiogenic factors.
        Science. 1987; 235: 442
        • Border W.A.
        • Ruoslahti E.
        Transforming growth factor-β in disease: the dark side of tissue repair.
        J Clin Invest. 1992; 90: 1
        • Chang J.
        • Thunder R.
        • Most D.
        • Longaker M.T.
        • Lineaweaver W.C.
        Studies in flexor tendon wound healing: neutralizing antibody to TGF-beta1 increases postoperative range of motion.
        Plast Reconstr Surg. Jan 2000; 105: 148
        • Gurtner G.C.
        • Callaghan M.J.
        • Longaker M.T.
        Progress and potential for regenerative medicine.
        Annu Rev Med. 2007; 58: 299
        • Awad H.A.
        • Butler D.L.
        • Boivin G.P.
        • et al.
        Autologous mesenchymal stem cell-mediated repair of tendon.
        Tissue Eng. 1999; 5: 267
        • Young R.G.
        • Butler D.L.
        • Weber W.
        • et al.
        Use of mesenchymal stem cells in a collagen matrix for Achilles tendon repair.
        J Orthop Res. 1998; 16: 406
        • Juncosa-Melvin N.
        • Boivin G.P.
        • Gooch C.
        • 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; 12: 369
        • Zuk P.A.
        • Zhu M.
        • Mizuno H.
        • et al.
        Multilineage cells from human adipose tissue: implications for cell-based therapies.
        Tissue Eng. 2001; 7: 211
        • Mizuno H.
        • Zuk P.A.
        • Zhu M.
        • Lorenz H.P.
        • Benhaim P.
        • Hedrick M.H.
        Myogenic differentiation by human processed lipoaspirate cells.
        Plast Reconstr Surg. Jan 2002; 109: 199
        • Tobita M.
        • Uysal A.C.
        • Ogawa R.
        • Hyakusoku H.
        • Mizuno H.
        Periodontal tissue regeneration with adipose-derived stem cells.
        Tissue Eng Part A. Jun 2008; 14: 945
        • Ogawa R.
        • Mizuno H.
        • Watanabe A.
        • Migita M.
        • Shimada T.
        • Hyakusoku H.
        Osteogenic and chondrogenic differentiation by adipose-derived stem cells harvested from GFP transgenic mice.
        Biochem Biophys Res Commun. 2004 Jan 23; 313: 871
        • Lu F.
        • Mizuno H.
        • Uysal C.A.
        • Cai X.
        • Ogawa R.
        • Hyakusoku H.
        Improved viability of random pattern skin flaps through the use of adipose-derived stem cells.
        Plast Reconstr Surg. Jan 2008; 121: 50
        • Koike T.
        • Noguchi Y.
        • Imai H.
        Histological comparison of platelet-rich plasma and enamel matrix derivative on periodontal regeneration in rats.
        Shika Igaku. 2004; 67: 37
        • Uysal C.A.
        • Ogawa R.
        • Tobita M.
        • Hyakusoku H.
        • Mizuno H.
        The effect of adipose derived stem cells on ischemia reperfusion injury: immunohistochemical and ultrastructural evaluation.
        Plast Reconstr Surg. Sep 2009; 124: 804
        • Hanz K.R.
        • Saint-Cyr M.
        • Semmler M.J.
        • Rohrich R.J.
        Extensor tendon injuries: acute management and secondary reconstruction.
        Plast Reconstr Surg. 2008; 121: 109e
        • Soni P.
        • Stern C.A.
        • Foreman K.B.
        • Rockwell W.B.
        Advances in extensor tendon diagnosis and therapy.
        Plast Reconstr Surg. 2009; 123: 727
        • James R.
        • Kesturu G.
        • Balian G.
        • Chhabra A.B.
        Tendon: biology, biomechanics, repair, growth factors, and evolving treatment options.
        J Hand Surg [Am]. 2008; 33: 102
        • Vucekovich K.
        • Gallardo G.
        • Fiala K.
        Rehabilitation after flexor tendon repair, reconstruction, and tenolysis.
        Hand Clin. 2005; 21: 257
        • Tang J.B.
        Clinical outcomes associated with flexor tendon repair.
        Hand Clin. 2005; 21: 199
        • Piskin A.
        • Yuceturk A.
        • Tomak Y.
        • et al.
        Tendon repair with the strengthened modified Kessler, modified Kessler, and Savage suture techniques: a biomechanical comparison.
        Acta Orthop Traumatol Turc. 2007; 41: 238
        • Robertson G.A.
        • Al-Qattan M.M.
        A biomechanical analysis of a new interlock suture technique for flexor tendon repair.
        J Hand Surg. 1992; 17B: 92
        • Strickland J.W.
        Flexor tendons-acute injuries.
        in: Green D.P. Hotchkiss R. Pederson W.C. Green's operative hand surgery. 4th ed. Churchill Livingstone, 1999: 1851-1897
        • Ion L.E.
        • Sykes P.J.
        • Cassell O.C.S.
        • O'Doherty D.M.
        • Roberts A.M.
        Comparative biomechanical analysis of a new circumferential flexor tendon repair and a modified Kessler repair.
        Br J Plast Surg. 1997; 50: 236
        • Woo S.H.
        • Tsai T.M.
        • Kleinert H.E.
        • Chew W.Y.
        • Voor M.J.
        A biomechanical comparison of four extensor tendon repair techniques in zone IV.
        Plast Reconstr Surg. 2005; 115: 1674
        • Smith A.M.
        • Evans D.M.
        Biomechanical assessment of a new type of flexor tendon repair.
        J Hand Surg [Br]. Jun 2001; 26: 217
        • Kajikawa Y.
        • Morihara T.
        • Sakamoto H.
        • et al.
        Platelet-rich plasma enhances the initial mobilization of circulation-derived cells for tendon healing.
        J Cell Physiol. 2008; 215: 837
        • Eriksen H.A.
        • Pajala A.
        • Leppilahti J.
        • Risteli J.
        Increased content of type III collagen at the rupture site of human Achilles tendon.
        J Orthop Res. 2002; 20: 1352
        • Tang J.B.
        • Xu Y.
        • Ding F.
        • Wang X.T.
        Expression of genes for collagen production and NF-kappaB gene activation of in vivo healing flexor tendons.
        J Hand Surg [Am]. 2004; 29: 564
        • Butler D.L.
        • Juncosa-Melvin N.
        • Boivin G.P.
        • et al.
        Functional tissue engineering for tendon repair: a multidisciplinary strategy using mesenchymal stem cells, bioscaffolds, and mechanical stimulation.
        J Orthop Res. 2008; 26: 1
        • Juncosa-Melvin N.
        • Matlin K.S.
        • Holdcraft R.W.
        • Nirmalanandhan V.S.
        • Butler D.L.
        Mechanical stimulation increases collagen type I and collagen type III gene expression of stem cell-collagen sponge constructs for patellar tendon repair.
        Tissue Eng. 2007; 13: 1219
        • Chang J.
        • Most D.
        • Stelnicki E.
        • et al.
        Gene expression of transforming growth factor beta-1 in rabbit zone II flexor tendon wound healing: evidence for dual mechanisms of repair.
        Plast Reconstr Surg. 1997; 100: 937
        • Zhang A.Y.
        • Pham H.
        • Ho F.
        • Teng K.
        • Longaker M.T.
        • Chang J.
        Inhibition of TGF-beta-induced collagen production in rabbit flexor tendons.
        J Hand Surg [Am]. 2004; 29: 230
        • Woo S.L.
        • Hildebrand K.
        • Watanabe N.
        • Fenwick J.A.
        • Papageorgiou C.D.
        • Wang J.H.
        Tissue engineering of ligament and tendon healing.
        Clin Orthop Relat Res. 1999; 367: S312
        • Hildebrand K.A.
        • Woo S.L.
        • Smith D.W.
        • et al.
        The effects of platelet-derived growth factor-BB on healing of the rabbit medial collateral ligament. An in vivo study.
        Am J Sports Med. 1998; 26: 549
        • Chang J.
        • Most D.
        • Thunder R.
        • Mehrara B.
        • Longaker M.T.
        • Lineaweaver W.C.
        Molecular studies in flexor tendon wound healing: the role of basic fibroblast growth factor gene expression.
        J Hand Surg [Am]. 1998; 23: 1052
        • Hsu C.
        • Chang J.
        Clinical implications of growth factors in flexor tendon wound healing.
        J Hand Surg [Am]. 2004; 29: 551
        • Marx R.E.
        Platelet-rich plasma: evidence to support its use.
        J Oral Maxillofac Surg. 2004; 62: 489
        • Harrison P.
        • Cramer E.M.
        Platelet alpha-granules.
        Blood Rev. 1993; 7: 52
        • Weibrich G.
        • Kleis W.K.
        • Hafner G.
        • Hitzler W.E.
        Growth factor levels in platelet-rich plasma and correlations with donor age, sex, and platelet count.
        J Craniomaxillofac Surg. 2002; 30: 97
        • Tozum T.F.
        • Demiralp B.
        Platelet-rich plasma: a promising innovation in dentistry.
        J Can Dent Assoc. 2003; 69: 664
        • Caplan A.I.
        Review: mesenchymal stem cells: cell-based reconstructive therapy in orthopedics.
        Tissue Eng. 2005; 11: 1198
        • Juncosa-Melvin N.
        • Boivin G.P.
        • Galloway M.T.
        • et al.
        Effects of cell-to-collagen ratio in mesenchymal stem cell-seeded implants on tendon repair biomechanics and histology.
        Tissue Eng. 2005; 11: 448
        • Hoffmann A.
        • Gross G.
        Tendon and ligament engineering: from cell biology to in vivo application.
        Regen Med. 2006; 1: 563
        • Juncosa-Melvin N.
        • Shearn J.T.
        • Boivin G.P.
        • et al.
        Effects of mechanical stimulation on the biomechanics and histology of stem cell-collagen sponge constructs for rabbit patellar tendon repair.
        Tissue Eng. 2006; 12: 2291
        • Juncosa-Melvin N.
        • Boivin G.P.
        • Galloway M.T.
        • Gooch C.
        • West J.R.
        • Butler D.L.
        Effects of cell-to-collagen ratio in stem cell-seeded constructs for Achilles tendon repair.
        Tissue Eng. 2006; 12: 681
        • Cao Y.
        • Liu Y.
        • Liu W.
        • Shan Q.
        • Buonocore S.D.
        • Cui L.
        Bridging tendon defects using autologous tenocyte engineered tendon in a hen model.
        Plast Reconstr Surg. 2002; 110: 1280
        • Cao Y.
        • Vacanti J.P.
        • Ma X.
        • et al.
        Generation of neo-tendon using synthetic polymers seeded with tenocytes.
        Transplant Proc. Dec 1994; 26: 3390
        • Liu W.
        • Chen B.
        • Deng D.
        • Xu F.
        • Cui L.
        • Cao Y.
        Repair of tendon defect with dermal fibroblast engineered tendon in a porcine model.
        Tissue Eng. 2006; 12: 775
        • Tapp H.
        • Hanley Jr., E.N.
        • Patt J.C.
        • Gruber H.E.
        Adipose-derived stem cells: characterization and current application in orthopaedic tissue repair.
        Exp Biol Med (Maywood). 2009; 234: 1
        • Uysal A.C.
        • Mizuno H.
        Tendon regeneration and repair with adipose derived stem cells.
        Curr Stem Cell Res Ther. 2010; 5: 161-167
        • Uysal A.C.
        • Mizuno H.
        Differentiation of adipose-derived stem cells for tendon repair.
        Methods Mol Biol. 2011; 702: 443-451