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

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.

[1]  R. Ogawa,et al.  The Effect of Adipose-Derived Stem Cells on Ischemia-Reperfusion Injury: Immunohistochemical and Ultrastructural Evaluation , 2009, Plastic and reconstructive surgery.

[2]  M. Longaker,et al.  Differential expression of transforming growth factor-beta receptors in a rabbit zone II flexor tendon wound healing model. , 2001, Plastic and reconstructive surgery.

[3]  K. Foreman,et al.  Advances in Extensor Tendon Diagnosis and Therapy , 2009, Plastic and reconstructive surgery.

[4]  H. Kleinert,et al.  A Biomechanical Comparison of Four Extensor Tendon Repair Techniques in Zone IV , 2005, Plastic and reconstructive surgery.

[5]  Natalia Juncosa-Melvin,et al.  Mechanical stimulation increases collagen type I and collagen type III gene expression of stem cell-collagen sponge constructs for patellar tendon repair. , 2007, Tissue engineering.

[6]  J. Vacanti,et al.  Generation of neo-tendon using synthetic polymers seeded with tenocytes. , 1994, Transplantation proceedings.

[7]  G. Hafner,et al.  Growth factor levels in platelet-rich plasma and correlations with donor age, sex, and platelet count. , 2002, Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery.

[8]  C. Frank,et al.  Collagen fibril diameters in the rabbit medial collateral ligament scar: a longer term assessment. , 1997, Connective tissue research.

[9]  Natalia Juncosa-Melvin,et al.  Functional tissue engineering for tendon repair: A multidisciplinary strategy using mesenchymal stem cells, bioscaffolds, and mechanical stimulation , 2008, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[10]  R. Marx Platelet-rich plasma: evidence to support its use. , 2004, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[11]  Michael T Longaker,et al.  Progress and potential for regenerative medicine. , 2007, Annual review of medicine.

[12]  R. Gelberman,et al.  Growth factors and canine flexor tendon healing: initial studies in uninjured and repair models. , 1995, The Journal of hand surgery.

[13]  A. Caplan Review: mesenchymal stem cells: cell-based reconstructive therapy in orthopedics. , 2005, Tissue engineering.

[14]  M. Hedrick,et al.  Myogenic Differentiation by Human Processed Lipoaspirate Cells , 2002, Plastic and reconstructive surgery.

[15]  Natalia Juncosa-Melvin,et al.  Effects of cell-to-collagen ratio in stem cell-seeded constructs for Achilles tendon repair. , 2006, Tissue engineering.

[16]  Yilin Cao,et al.  Bridging tendon defects using autologous tenocyte engineered tendon in a hen model. , 2002, Plastic and reconstructive surgery.

[17]  Rod J. Rohrich,et al.  Extensor tendon injuries: acute management and secondary reconstruction. , 2008, Plastic and reconstructive surgery.

[18]  Yan Xu,et al.  Expression of genes for collagen production and NF-kappaB gene activation of in vivo healing flexor tendons. , 2004, The Journal of hand surgery.

[19]  Max R. Lehfeldt,et al.  MOC-PS(SM) CME Article: Treatment of Flexor Tendon Laceration , 2008, Plastic and reconstructive surgery.

[20]  S. Woo,et al.  Tissue engineering of ligament and tendon healing. , 1999, Clinical orthopaedics and related research.

[21]  R. Ogawa,et al.  Improved Viability of Random Pattern Skin Flaps through the Use of Adipose-Derived Stem Cells , 2008, Plastic and reconstructive surgery.

[22]  J. Risteli,et al.  Increased content of type III collagen at the rupture site of human Achilles tendon , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[23]  M. Ozer,et al.  [Tendon repair with the strengthened modified Kessler, modified Kessler, and Savage suture techniques: a biomechanical comparison]. , 2007, Acta orthopaedica et traumatologica turcica.

[24]  M. Longaker,et al.  Inhibition of TGF-β-induced collagen production in rabbit flexor tendons , 2004 .

[25]  G. Schultz,et al.  Growth factors and wound healing: biochemical properties of growth factors and their receptors. , 1993, American journal of surgery.

[26]  T. Kubo,et al.  Platelet‐rich plasma enhances the initial mobilization of circulation‐derived cells for tendon healing , 2008, Journal of cellular physiology.

[27]  G. Robertson,et al.  A Biomechanical Analysis of a New Interlock Suture Technique for Flexor Tendon Repair , 1992, Journal of hand surgery.

[28]  Kathy Vucekovich,et al.  Rehabilitation after flexor tendon repair, reconstruction, and tenolysis. , 2005, Hand clinics.

[29]  W. Liu,et al.  Repair of tendon defect with dermal fibroblast engineered tendon in a porcine model. , 2006, Tissue engineering.

[30]  Natalia 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. , 2006, Tissue engineering.

[31]  D L Butler,et al.  Autologous mesenchymal stem cell-mediated repair of tendon. , 1999, Tissue engineering.

[32]  D. Butler,et al.  Use of mesenchymal stem cells in a collagen matrix for achilles tendon repair , 1998, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[33]  H. Mizuno,et al.  Differentiation of adipose-derived stem cells for tendon repair. , 2011, Methods in molecular biology.

[34]  M. Migita,et al.  Osteogenic and chondrogenic differentiation by adipose-derived stem cells harvested from GFP transgenic mice. , 2004, Biochemical and biophysical research communications.

[35]  Natalia Juncosa-Melvin,et al.  Effects of mechanical stimulation on the biomechanics and histology of stem cell-collagen sponge constructs for rabbit patellar tendon repair. , 2006, Tissue engineering.

[36]  E. Ruoslahti,et al.  Transforming growth factor-beta in disease: the dark side of tissue repair. , 1992, The Journal of clinical investigation.

[37]  T. Tözüm,et al.  Platelet-rich plasma: a promising innovation in dentistry. , 2003, Journal.

[38]  M. Boyer Green's Operative Hand Surgery, 4th ed , 1999 .

[39]  R B Evans,et al.  The application of force to the healing tendon. , 1993, Journal of hand therapy : official journal of the American Society of Hand Therapists.

[40]  D. O'Doherty,et al.  Comparative biomechanical analysis of a new circumferential flexor tendon repair and a modified Kessler repair. , 1997, British journal of plastic surgery.

[41]  H. Lorenz,et al.  Multilineage cells from human adipose tissue: implications for cell-based therapies. , 2001, Tissue engineering.

[42]  J. Tang,et al.  Clinical outcomes associated with flexor tendon repair. , 2005, Hand clinics.

[43]  Hiko Hyakusoku,et al.  Periodontal tissue regeneration with adipose-derived stem cells. , 2008, Tissue engineering. Part A.

[44]  S L Woo,et al.  The Effects of Platelet-Derived Growth Factor-BB on Healing of the Rabbit Medial Collateral Ligament , 1998, The American journal of sports medicine.

[45]  A. Hoffmann,et al.  Tendon and ligament engineering: from cell biology to in vivo application. , 2006, Regenerative medicine.

[46]  M. Longaker,et al.  Gene Expression of Transforming Growth Factor Beta‐1 in Rabbit Zone II Flexor Tendon Wound Healing: Evidence for Dual Mechanisms of Repair , 1997, Plastic and reconstructive surgery.

[47]  James Chang,et al.  Clinical implications of growth factors in flexor tendon wound healing. , 2004, The Journal of hand surgery.

[48]  G. Balian,et al.  Tendon: biology, biomechanics, repair, growth factors, and evolving treatment options. , 2008, The Journal of hand surgery.

[49]  D. Evans,et al.  Biomechanical Assessment of a New Type of Flexor Tendon Repair , 2001, Journal of hand surgery.

[50]  M. Longaker,et al.  Molecular studies in flexor tendon wound healing: the role of basic fibroblast growth factor gene expression. , 1998, The Journal of hand surgery.

[51]  Peter Harrison,et al.  Platelet a-granules , 1993 .

[52]  H. Mizuno,et al.  Tendon regeneration and repair with adipose derived stem cells , 2010 .

[53]  M. Longaker,et al.  Studies in Flexor Tendon Wound Healing: Neutralizing Antibody to TGF‐&bgr;1 Increases Postoperative Range of Motion , 2000, Plastic and reconstructive surgery.

[54]  Natalia Juncosa-Melvin,et al.  Effects of cell-to-collagen ratio in mesenchymal stem cell-seeded implants on tendon repair biomechanics and histology. , 2005, Tissue engineering.

[55]  H. Gruber,et al.  Adipose-Derived Stem Cells: Characterization and Current Application in Orthopaedic Tissue Repair , 2009, Experimental biology and medicine.