期刊论文详细信息
Stem Cell Research & Therapy
Effect of a single injection of autologous conditioned serum (ACS) on tendon healing in equine naturally occurring tendinopathies
Peter M. Stadler2  Karl Rohn3  Andreas Beineke1  Maren Lietzau2  Florian Geburek2 
[1] Institute for Pathology, University of Veterinary Medicine Hannover, Foundation, Bünteweg 17, Hannover, 30559, Germany;Equine Clinic, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, Hannover, 30559, Germany;Institute for Biometry, Epidemiology and Information Processing, University of Veterinary Medicine Hannover, Foundation, Bünteweg 2, Hannover, 30559, Germany
关键词: Irap;    ACS;    Autologous conditioned serum;    Collagen;    Histology;    Biopsy;    Ultrasonography;    Tendon;    Horse;   
Others  :  1221161
DOI  :  10.1186/s13287-015-0115-0
 received in 2014-10-27, accepted in 2015-06-11,  发布年份 2015
PDF
【 摘 要 】

Introduction

Autologous blood-derived biologicals, including autologous conditioned serum (ACS), are frequently used to treat tendinopathies in horses despite limited evidence for their efficacy. The purpose of this study was to describe the effect of a single intralesional injection of ACS in naturally occurring tendinopathies of the equine superficial digital flexor tendon (SDFT) on clinical, ultrasonographic, and histological parameters.

Methods

Fifteen horses with 17 naturally occurring tendinopathies of forelimb SDFTs were examined clinically and ultrasonographically (day 0). Injured tendons were randomly assigned to the ACS-treated group (n = 10) receiving a single intralesional ACS injection or included as controls (n = 7) which were either untreated or injected with saline on day 1. All horses participated in a gradually increasing exercise programme and were re-examined nine times at regular intervals until day 190. Needle biopsies were taken from the SDFTs on days 0, 36 and 190 and examined histologically and for the expression of collagen types I and III by immunohistochemistry.

Results

In ACS-treated limbs lameness decreased significantly until day 10 after treatment. Swelling (scores) of the SDFT region decreased within the ACS group between 50 and 78 days after treatment. Ultrasonographically, the percentage of the lesion in the tendon was significantly lower and the echogenicity of the lesion (total echo score) was significantly higher 78 and 106 days after intralesional ACS injection compared to controls. Histology revealed that, compared to controls, tenocyte nuclei were more spindle-shaped 36 days after ACS injection. Immunohistochemistry showed that collagen type I expression significantly increased between days 36 and 190 after ACS injection.

Conclusions

Single intralesional ACS injection of equine SDFTs with clinical signs of acute tendinopathy contributes to an early significant reduction of lameness and leads to temporary improvement of ultrasonographic parameters of repair tissue. Intralesional ACS treatment might decrease proliferation of tenocytes 5 weeks after treatment and increase their differentiation as demonstrated by elevated collagen type I expression in the remodelling phase. Potential enhancement of these effects by repeated injections should be tested in future controlled clinical investigations.

【 授权许可】

   
2015 Geburek et al.

【 预 览 】
附件列表
Files Size Format View
20150727103841256.pdf 1874KB PDF download
Fig. 4. 61KB Image download
Fig. 3. 198KB Image download
Fig. 2. 100KB Image download
Fig. 1. 59KB Image download
【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

【 参考文献 】
  • [1]Patterson-Kane JC, Firth EC: The pathobiology of exercise-induced superficial digital flexor tendon injury in Thoroughbred racehorses. Vet J. 2009, 181:79-89.
  • [2]Avella CS, Smith RKW: Diagnosis and management of tendon and ligament disorders. In Equine Surgery. 4th edition. Edited by Auer JA, Stick JA. Elsevier Saunders, St. Louis, Missouri, USA; 2011:1157-79.
  • [3]Geburek F, Stadler P: Regenerative therapy for tendon and ligament disorders in horses. Terminology, production, biologic potential and in vitro effects. Tieraerztliche Praxis Ausgabe Grosstiere Nutztiere 2011, 39:373-83.
  • [4]Lopez MJ, Jarazo J: State of the art: stem cells in equine regenerative medicine. Equine Vet J. 2015, 47:145-54.
  • [5]Smith RK, Werling NJ, Dakin SG, Alam R, Goodship AE, Dudhia J: Beneficial effects of autologous bone marrow-derived mesenchymal stem cells in naturally occurring tendinopathy. PLoS One. 2013., 8Article ID e75697
  • [6]Carvalho AD, Badial PR, Alvarez LEC, Yamada ALM, Borges AS, Deffune E, et al.: Equine tendonitis therapy using mesenchymal stem cells and platelet concentrates: a randomized controlled trial. Stem Cell Res Ther. 2013, 4:85. BioMed Central Full Text
  • [7]Bosch G, van Schie HT, de Groot MW, Cadby JA, van de Lest CH, Barneveld A, et al.: Effects of platelet-rich plasma on the quality of repair of mechanically induced core lesions in equine superficial digital flexor tendons: a placebo-controlled experimental study. J Orthop Res. 2010, 28:211-7.
  • [8]Textor J: Autologous biologic treatment for equine musculoskeletal injuries: platelet-rich plasma and IL-1 receptor antagonist protein. Vet Clin North Am Equine Pract. 2011, 27:275-98.
  • [9]Ionita JC, Brehm W: Autologe Blutprodukte in der Regenerativen Therapie: ACS, PRP, ACP, Knochenmark (Autologous blood products for regenerative therapies: ACS, PRP, ACP, bone marrow). In Pferdeheilkunde Forum 2008 - Berliner Fortbildungstage. Edited by Lauk HD. Hippiatrika Verlag, Berlin, Germany; 2008:588-91.
  • [10]Weinberger T: Regenerative Therapiemöglichkeiten beim Pferd - eine Übersicht (Regenerative treatment options in horses - an overview). Pferde Spiegel. 2008, 11:116-9.
  • [11]Meijer H, Reinecke J, Becker C, Tholen G, Wehling P: The production of anti-inflammatory cytokines in whole blood by physico-chemical induction. Inflamm Res. 2003, 52:404-7.
  • [12]Hraha TH, Doremus KM, McIlwraith CW, Frisbie DD: Autologous conditioned serum: the comparative cytokine profiles of two commercial methods (IRAP and IRAP II) using equine blood. Equine Vet J. 2011, 43:516-21.
  • [13]Frisbie DD, Kawcak CE, Werpy NM, Park RD, McIlwraith CW: Clinical, biochemical, and histologic effects of intra-articular administration of autologous conditioned serum in horses with experimentally induced osteoarthritis. Am J Vet Res. 2007, 68:290-6.
  • [14]Dahlgren LA, van der Meulen MC, Bertram JE, Starrak GS, Nixon AJ: Insulin-like growth factor-I improves cellular and molecular aspects of healing in a collagenase-induced model of flexor tendinitis. J Orthop Res. 2002, 20:910-9.
  • [15]Molloy T, Wang Y, Murrell G: The roles of growth factors in tendon and ligament healing. Sports Med. 2003, 33:381-94.
  • [16]Heisterbach PE, Todorov A, Fluckiger R, Evans CH, Majewski M: Effect of BMP-12, TGF-beta1 and autologous conditioned serum on growth factor expression in Achilles tendon healing. Knee Surg Sports Traumatol Arthrosc. 2012, 20:1907-14.
  • [17]Dahlgren LA, Harvey SC: Effect of autologous conditioned serum on the metabolism of normal tendon explants. In 54th Annual Meeting of the Orthopaedic Research Society; March 2–5. Orthopaedic Research Society, Rosemont, IL, USA; 2008. Poster No. 770
  • [18]Wright-Carpenter T, Opolon P, Appell HJ, Meijer H, Wehling P, Mir LM: Treatment of muscle injuries by local administration of autologous conditioned serum: animal experiments using a muscle contusion model. Int J Sports Med. 2004, 25:582-7.
  • [19]Baltzer AW, Moser C, Jansen SA, Krauspe R: Autologous conditioned serum (Orthokine) is an effective treatment for knee osteoarthritis. Osteoarthritis Cartilage. 2009, 17:152-60.
  • [20]Sun HB, Li Y, Fung DT, Majeska RJ, Schaffler MB, Flatow EL: Coordinate regulation of IL-1beta and MMP-13 in rat tendons following subrupture fatigue damage. Clin Orthop Relat Res. 2008, 466:1555-61.
  • [21]Dakin SG, Dudhia J, Smith RKW. Modulation of prostaglandin E2 production in equine tendon cells. In: 49th British Equine Veterinary Association Congress; September 8–11. Newmarket, England: Equine Veterinary Journal, Ltd; 2010. p. 96.
  • [22]Majewski M, Ochsner PE, Liu F, Fluckiger R, Evans CH: Accelerated healing of the rat Achilles tendon in response to autologous conditioned serum. Am J Sports Med. 2009, 37:2117-25.
  • [23]Jann H, Stashak TS: Tendon and Paratendon Lacerations. In Equine Wound Management. Edited by Stashak TS, Theoret CL. Wiley-Blackwell, Ames, Iowa, USA; 2008:489-508.
  • [24]Edinger J: Orthopädische Untersuchung der Gliedmaβen und der Wirbelsäule (Orthopaedic examination of the limbs and the vertebral column). In Praxisorientierte Anatomie und Propädeutik des Pferdes (Practical anatomy and propaedeutics of the horse). Edited by Wissdorf H, Gerhards H, Huskamp B, Deegen E. M. u. H. Schaper, Hannover; 2010:890-926.
  • [25]Schmidt H: Die Behandlung akuter und chronischer Sehnenerkrankungen beim Pferd mit hochmolekularer Hyaluronsäure (The treatment of acute and chronic tendon injuries in the horse with high molecular weight hyaluronic acid). Dr. med. vet. thesis. Hannover, Germany, Tierärztliche Hochschule Hannover; 1989.
  • [26]Genovese RL, Rantanen NW, Hauser ML, Simpson BS: Diagnostic ultrasonography of equine limbs. Vet Clin North Am Equine Pract. 1986, 2:145-226.
  • [27]Rantanen NW, Jorgensen JS, Genovese RL: Ultrasonographic evaluation of the equine limb: technique. In Diagnosis and Management of Lameness in the Horse. 1st edition. Edited by Ross MW, Dyson SJ. Elsevier, St. Louis; 2003:166-88.
  • [28]Reef VB, Genovese RL, Davis WM: Initial long-term results of horses with superficial flexor tendinitis treated with intralesional beta-aminoproprionitrile fumarate. In 43rd Annual Convention of the AAEP; December 7–10. American Association of Equine Practitioners, Lexington, KY, USA; 1997:301-5.
  • [29]Wagels R, Ruhmann K, Stadler P, Drommer W: Percutaneous core biopsy of the flexor tendons in the horse. Tierarztl Prax G N. 2001, 29:199-205.
  • [30]Astrom M, Rausing A: Chronic Achilles tendinopathy. A survey of surgical and histopathologic findings. Clin Orthop Relat Res 1995, 316:151-64.
  • [31]Alldinger S, Wunschmann A, Baumgartner W, Voss C, Kremmer E: Up-regulation of major histocompatibility complex class II antigen expression in the central nervous system of dogs with spontaneous canine distemper virus encephalitis. Acta Neuropathol. 1996, 92:273-80.
  • [32]Kummerfeld M, Seehusen F, Klein S, Ulrich R, Kreutzer R, Gerhauser I, et al.: Periventricular demyelination and axonal pathology is associated with subependymal virus spread in a murine model for multiple sclerosis. Intervirology. 2012, 55:401-16.
  • [33]Ulrich R, Baumgartner W, Gerhauser I, Seeliger F, Haist V, Deschl U, et al.: MMP-12, MMP-3, and TIMP-1 are markedly upregulated in chronic demyelinating theiler murine encephalomyelitis. J Neuropathol Exp Neurol. 2006, 65:783-93.
  • [34]Dahlgren LA, Mohammed HO, Nixon AJ: Temporal expression of growth factors and matrix molecules in healing tendon lesions. J Orthop Res. 2005, 23:84-92.
  • [35]Chuen FS, Chuk CY, Ping WY, Nar WW, Kim HL, Ming CK: Immunohistochemical characterization of cells in adult human patellar tendons. J Histochem Cytochem. 2004, 52:1151-7.
  • [36]Birch HL, Bailey AJ, Goodship AE: Macroscopic ‘degeneration’ of equine superficial digital flexor tendon is accompanied by a change in extracellular matrix composition. Equine Vet J. 1998, 30:534-9.
  • [37]van Schie HT, Bakker EM, Cherdchutham W, Jonker AM, van de Lest CH, van Weeren PR: Monitoring of the repair process of surgically created lesions in equine superficial digital flexor tendons by use of computerized ultrasonography. Am J Vet Res. 2009, 70:37-48.
  • [38]van Schie HT, Bakker EM, Jonker AM, van Weeren PR: Computerized ultrasonographic tissue characterization of equine superficial digital flexor tendons by means of stability quantification of echo patterns in contiguous transverse ultrasonographic images. Am J Vet Res. 2003, 64:366-75.
  • [39]Kasashima Y, Takahashi T, Smith RK, Goodship AE, Kuwano A, Ueno T, et al.: Prevalence of superficial digital flexor tendonitis and suspensory desmitis in Japanese Thoroughbred flat racehorses in 1999. Equine Vet J. 2004, 36:346-50.
  • [40]van Schie JT, Bakker EM, van Weeren PR: Ultrasonographic evaluation of equine tendons: a quantitative in vitro study of the effects of amplifier gain level, transducer-tilt, and transducer-displacement. Vet Radiol Ultrasound. 1999, 40:151-60.
  • [41]Movin T, Guntner P, Gad A, Rolf C: Ultrasonography-guided percutaneous core biopsy in Achilles tendon disorder. Scand J Med Sci Sports. 1997, 7:244-8.
  • [42]Movin T: Tendon tissue sampling. Scand J Med Sci Sports. 2000, 10:368-71.
  • [43]Buck C, Drommer W, Wagels R, Stadler P: Scanning electron microscopy examination of tendon biopsies in healthy horses and patients with different stages of tendon healing. Pferdeheilkunde. 2002, 18:521-8.
  • [44]Sodersten F, Hultenby K, Heinegard D, Johnston C, Ekman S: Immunolocalization of collagens (I and III) and cartilage oligomeric matrix protein in the normal and injured equine superficial digital flexor tendon. Connect Tissue Res. 2013, 54:62-9.
  • [45]Henninger RW, Bramlage RW, Bailey M, Bertone AL, Weisbrode SE: Effects of tendon splitting on experimentally-induced acute equine tendinitis. Vet Comp Orthop Traumatol. 1992, 1:5-13.
  • [46]Meershoek LS, Lanovaz JL, Schamhardt HC, Clayton HM: Calculated forelimb flexor tendon forces in horses with experimentally induced superficial digital flexor tendinitis and the effects of application of heel wedges. Am J Vet Res. 2002, 63:432-7.
  • [47]Ross MW: Movement. In Diagnosis and Management of Lameness in the Horse. 2nd edition. Edited by Ross MW, Dyson SJ. Elsevier Saunders, St. Louis; 2011:64-80.
  • [48]Turner TA: Thermography as an aid to the clinical lameness evaluation. Vet Clin North Am Equine Pract. 1991, 7:311-38.
  • [49]Boehart S, Arndt G, Carstanjen B: Ultrasonographic morphometric measurements of digital flexor tendons and ligaments of the palmar metacarpal region in Haflinger horses. Anat Histol Embryol. 2010, 39:366-75.
  • [50]Gillis CL: Rehabilitation of Tendon and Ligament Injuries. In 43rd Annual Convention of the AAEP; December 7–10. American Association of Equine Practitioners, Lexington, KY, USA; 1997:306-9.
  • [51]Silver IA, Brown PN, Goodship AE, Lanyon LE, McCullagh KG, Perry GC, et al.: A clinical and experimental study of tendon injury, healing and treatment in the horse. Equine Vet J Suppl. 1983, 1:1-43.
  • [52]Nixon AJ, Saxer RA, Brower-Toland BD: Exogenous insulin-like growth factor-I stimulates an autoinductive IGF-I autocrine/paracrine response in chondrocytes. J Orthop Res. 2001, 19:26-32.
  文献评价指标  
  下载次数:23次 浏览次数:4次