Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

Evaluation of adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells for treatment of osteoarthritis.

Journal of orthopaedic research : official publication of the Orthopaedic Research Society June 23, 2009 Volume 27, Issue 12 1675-1680 doi: 10.1002/jor.20933

Frisbie DD, Kisiday JD, Kawcak CE, Werpy NM, McIlwraith CW.The purpose of this study was the assessment of clinical, biochemical, and histologic effects of intraarticular administered adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells for treatment of osteoarthritis. Osteoarthritis was induced arthroscopically in the middle carpal joint of all horses, the contralateral joint being sham-operated. All horses received treatment on Day 14. Eight horses received placebo treatment and eight horses received adipose-derived stromal vascular fraction in their osteoarthritis-affected joint. The final eight horses were treate...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society November 16, 2006 Volume 25, Issue 2 230-240 doi: 10.1002/jor.20278

Schnabel LV, Mohammed HO, Miller BJ, McDermott WG, Jacobson MS, Santangelo KS, Fortier LA.Platelet rich plasma (PRP) has recently been investigated for use in tissue regeneration studies that seek to utilize the numerous growth factors released from platelet alpha-granules. This study examined gene expression patterns, DNA, and collagen content of equine flexor digitorum superficialis tendon (SDFT) explants cultured in media consisting of PRP and other blood products. Blood and bone marrow aspirate (BMA) were collected from horses and processed to obtain plasma, PRP, and platelet poor plasma (PPP). IGF-I, TGF-beta1, and PDGF-BB were quantified in all blood products using ELISA. Ten...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society April 8, 2009 Volume 27, Issue 10 1392-1398 doi: 10.1002/jor.20887

Schnabel LV, Lynch ME, van der Meulen MC, Yeager AE, Kornatowski MA, Nixon AJ.Tendinitis remains a catastrophic injury among athletes. Mesenchymal stem cells (MSCs) have recently been investigated for use in the treatment of tendinitis. Previous work has demonstrated the value of insulin-like growth factor-I (IGF-I) to stimulate cellular proliferation and tendon fiber deposition in the core lesion of tendinitis. This study examined the effects of MSCs, as well as IGF-I gene-enhanced MSCs (AdIGF-MSCs) on tendon healing in vivo. Collagenase-induced bilateral tendinitis lesions were created in equine flexor digitorum superficialis tendons (SDFT). Tendons were treated with ...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society April 4, 2007 Volume 25, Issue 7 913-925 doi: 10.1002/jor.20382

Wilke MM, Nydam DV, Nixon AJ.Mesenchymal stem cells (MSCs) provide an important source of pluripotent cells for musculoskeletal tissue repair. This study examined the impact of MSC implantation on cartilage healing characteristics in a large animal model. Twelve full-thickness 15-mm cartilage lesions in the femoropatellar articulations of six young mature horses were repaired by injection of a self-polymerizing autogenous fibrin vehicle containing mesenchymal stem cells, or autogenous fibrin alone in control joints. Arthroscopic second look and defect biopsy was obtained at 30 days, and all animals were euthanized 8 month...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society August 24, 2001 Volume 19, Issue 4 738-749 doi: 10.1016/S0736-0266(00)00054-1

Worster AA, Brower-Toland BD, Fortier LA, Bent SJ, Williams J, Nixon AJ.This study evaluated chondrogenesis of mesenchymal progenitor stem cells (MSCs) cultured initially under pre-confluent monolayer conditions exposed to transforming growth factor-beta1 (TGF-beta1), and subsequently in three-dimensional cultures containing insulin-like growth factor I (IGF-I). Bone marrow aspirates and chondrocytes were obtained from horses and cultured in monolayer with 0 or 5 ng of TGF-beta 1 per ml of medium for 6 days. TGF-beta 1 treated and untreated cultures were distributed to three-dimensional fibrin disks containing 0 or 100 ng of IGF-I per ml of medium to establish fou...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society August 29, 2009 Volume 28, Issue 2 211-217 doi: 10.1002/jor.20980

Bosch G, van Schie HT, de Groot MW, Cadby JA, van de Lest CH, Barneveld A, van Weeren PR.Tendon injuries are notorious for their slow and functionally inferior healing. Intratendinous application of platelet-rich plasma (PRP) has been reported to stimulate the repair process of tendon injuries, but there is little conclusive evidence for its effectiveness. A placebo-controlled experimental trial was performed to test the hypothesis that a single intratendinous PRP treatment enhances the quality of tendon repair, as evidenced by improved biochemical, biomechanical, and histological tissue properties. In six horses, tendon lesions were created surgically in the Superficial Digital F...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society October 26, 2007 Volume 26, Issue 3 322-331 doi: 10.1002/jor.20508

Kisiday JD, Kopesky PW, Evans CH, Grodzinsky AJ, McIlwraith CW, Frisbie DD.Bone marrow mesenchymal stem cells (BM-MSCs) and adipose-derived progenitor cells (ADPCs) are potential alternatives to autologous chondrocytes for cartilage resurfacing strategies. In this study, the chondrogenic potentials of these cell types were compared by quantifying neo-tissue synthesis and assaying gene expression and accumulation of extracellular matrix (ECM) components of cartilage. Adult equine progenitor cells encapsulated in agarose or self-assembling peptide hydrogels were cultured in the presence or absence of TGFbeta1 for 3 weeks. In BM-MSCs-seeded hydrogels, TGFbeta1 stimulate...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society October 18, 2002 Volume 20, Issue 5 910-919 doi: 10.1016/S0736-0266(02)00009-8

Dahlgren LA, van der Meulen MC, Bertram JE, Starrak GS, Nixon AJ.Flexor tendinitis is a common and debilitating injury of elite and recreational athletes. Healing may be improved through intratendinous injection of insulin-like growth factor-I (IGF-I), which has been shown in vitro to stimulate mitogenesis and enhance tendon matrix production. This study investigated the effects of intratendinous injection of IGF-I on tendon healing in an equine model of flexor tendinitis. Collagenase-induced lesions were created in the tensile region of theflexor digitorum superficialis tendon of both forelimbs of eight horses. Treated tendons were injected with 2 microg r...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society June 12, 2003 Volume 21, Issue 4 573-583 doi: 10.1016/S0736-0266(02)00264-4

Hidaka C, Goodrich LR, Chen CT, Warren RF, Crystal RG, Nixon AJ.Cartilage has a limited capacity to heal. Although chondrocyte transplantation is a useful therapeutic strategy, the repair process can be lengthy. Previously we have shown that over expression of bone morphogenetic protein-7 (BMP-7) in chondrocytes by adenovirus-mediated gene transfer leads to increased matrix synthesis and cartilage-like tissue formation in vitro. In this context we hypothesized that implantation of genetically modified chondrocytes expressing BMP-7 would accelerate the formation of hyaline-like repair tissue in an equine model of cartilage defect repair. Methods: Chondrocyt...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society December 21, 2004 Volume 23, Issue 1 118-126 doi: 10.1016/j.orthres.2004.06.020

Haupt JL, Frisbie DD, McIlwraith CW, Robbins PD, Ghivizzani S, Evans CH, Nixon AJ.This study evaluated the potential of gene induced synoviocyte expression of a combination of insulin-like growth factor-I (AdIGF-I) and interleukin-1 receptor antagonist protein (AdIL-1Ra) to control articular cartilage degradation in vitro. Cartilage explants and synovial membrane were harvested from young mature horses. Synovial monolayers were established and either (1) maintained as untransduced controls; (2) transduced with AdIGF-I at 200 MOI in 500 microl serum-free medium; (3) transduced with AdIL-1Ra at 100 MOI; or (4) transduced with a combination of AdIGF-I (200 MOI) and AdIL-1Ra (1...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society July 1, 1990 Volume 8, Issue 4 604-611 doi: 10.1002/jor.1100080417

Nunamaker DM, Butterweck DM, Provost MT.The North American Thoroughbred racehorse was chosen as a model to study the pathogenesis of fatigue failure of bone. This species has a high incidence of spontaneous fatigue failure of bone (bucked shins) during its early training. In vivo strain gauge studies of the third metacarpal bone of four young racehorses running at racing speeds showed high principal compressive strains [-4,841 +/- 572 (SD) microstrain] while two older horses had lower principal compressive strains (-3,317 microstrain measured at racing speed, -3,250 microstrain extrapolated from a slower speed run). Previously repor...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society July 1, 1994 Volume 12, Issue 4 485-497 doi: 10.1002/jor.1100120405

Hendrickson DA, Nixon AJ, Grande DA, Todhunter RJ, Minor RM, Erb H, Lust G.Cartilage resurfacing by chondrocyte implantation, with fibrin used as a vehicle, was examined in large (12 mm) full-thickness articular cartilage defects in horses. Articular chondrocytes, isolated from a 9-day-old foal, were mixed with fibrinogen and injected with thrombin, in a 1:1 mixture, into 12 mm circular defects on the lateral trochlea of the distal femur of eight normal horses. The contralateral femoropatellar (knee) joint served as a control in which the defect was left empty. Synovial fluid from the femoropatellar joints was sampled on days 0, 4, 7, 30, 120, and 240 postoperatively...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society November 1, 1994 Volume 12, Issue 6 822-833 doi: 10.1002/jor.1100120610

Les CM, Keyak JH, Stover SM, Taylor KT, Kaneps AJ.The purpose of this study was to investigate the relationships between data obtained from quantitative computed tomography and mechanical properties in the equine metacarpus, as measured in vitro in bone specimens. Three hundred and fifty-five bone specimens from the metacarpi of 10 horses were machined into right cylinders aligned with the long axis of the bone. A computed tomographic scan of the specimens, along with a Cann-Genant K2HPO4 calibration standard, was obtained. The specimens then were compressed to failure, and the elastic modulus, yield stress, yield strain, strain energy densit...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society March 18, 2013 Volume 31, Issue 7 1096-1102 doi: 10.1002/jor.22338

Becerra P, Valdés Vázquez MA, Dudhia J, Fiske-Jackson AR, Neves F, Hartman NG, Smith RK.This study aimed to investigate immediate cell survival and distribution following different administration routes of mesenchymal stem cells (MSCs) into naturally occurring tendon injuries. Ten million MSCs, labeled with technetium-99m hexamethylpropyleneamine oxime, were implanted into 13 horses with naturally occurring tendon or ligament injuries intra-lesionally, intravenously and by regional perfusion, and traced for up to 48 h using planar gamma scintigraphy. Labeling efficiencies varied between 1.8% and 18.5% (mean 9.3%). Cells were retained in the damaged area after intra-lesional adm...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society January 24, 2018 Volume 36, Issue 3 823-831 doi: 10.1002/jor.23738

McIlwraith CW, Kawcak CE, Frisbie DD, Little CB, Clegg PD, Peffers MJ, Karsdal MA, Ekman S, Laverty S, Slayden RA, Sandell LJ, Lohmander LS, Kraus VB.We report the results of a symposium aimed at identifying validated biomarkers that can be used to complement clinical observations for diagnosis and prognosis of joint injury leading to equine osteoarthritis (OA). Biomarkers might also predict pre-fracture change that could lead to catastrophic bone failure in equine athletes. The workshop was attended by leading scientists in the fields of equine and human musculoskeletal biomarkers to enable cross-disciplinary exchange and improve knowledge in both. Detailed proceedings with strategic planning was written, added to, edited and referenced to...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society April 29, 2019 Volume 37, Issue 6 1429-1439 doi: 10.1002/jor.24307

Polly SS, Nichols AEC, Donnini E, Inman DJ, Scott TJ, Apple SM, Werre SR, Dahlgren LA.Adipose-derived stromal vascular fraction (SVF) is a heterogeneous population of cells that yields a homogeneous population of plastic-adherent adipose tissue-derived stromal cells (ASC) when culture-expanded. SVF and ASC have been used clinically to improve tendon healing, yet their mechanism of action is not fully elucidated. The objective of this study was to investigate the potential for ASC to act as trophic mediators for tendon healing. Flexor digitorum superficialis tendons and adipose tissue were harvested from adult horses to obtain SVF, ASC, and tenocytes. Growth factor gene expressi...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society January 18, 2011 Volume 29, Issue 6 900-906 doi: 10.1002/jor.21332

Plaas A, Sandy JD, Liu H, Diaz MA, Schenkman D, Magnus RP, Bolam-Bretl C, Kopesky PW, Wang VM, Galante JO.We describe analysis of suspensory ligaments from horses with advanced degenerative suspensory ligament desmitis (DSLD) to identify the major proteoglycans (PGs), ADAMTS-aggrecanases and inter-alpha-trypsin inhibitor (IαI) components associated with ligament degeneration. Specific anatomical regions of suspensory ligaments from two normal horses and four diagnosed with DSLD were analyzed by Western blot and immunohistochemistry for the following: aggrecan, aggrecan fragments, decorin, ADAMTS4, ADAMTS5, and IαI components. When compared to normal, DSLD ligaments showed about a 15-fold increas...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society January 14, 2020 Volume 38, Issue 6 1365-1374 doi: 10.1002/jor.24584

Gilbertie JM, Schaer TP, Schubert AG, Jacob ME, Menegatti S, Ashton Lavoie R, Schnabel LV.Infectious arthritis is difficult to treat in both human and veterinary clinical practice. Recent literature reports Staphylococcus aureus as well as other gram-positive and gram-negative isolates forming free-floating biofilms in both human and equine synovial fluid that are tolerant to traditional antimicrobial therapy. Using an in vitro equine model, we investigated the ability of platelet-rich plasma (PRP) formulations to combat synovial fluid biofilm aggregates. Synovial fluid was infected, and biofilm aggregates allowed to form over a 2-hour period. PRP was collected and processed into d...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society February 5, 2008 Volume 26, Issue 6 764-771 doi: 10.1002/jor.20585

Ishihara A, Shields KM, Litsky AS, Mattoon JS, Weisbrode SE, Bartlett JS, Bertone AL.This study evaluated healing of equine metatarsal osteotomies and ostectomies in response to percutaneous injection of adenoviral (Ad) bone morphogenetic protein (BMP)-2, Ad-BMP-6, or beta-galactosidase protein vector control (Ad-LacZ) administered 14 days after surgery. Radiographic and quantitative computed tomographic assessment of bone formation indicated greater and earlier mineralized callus in both the osteotomies and ostectomies of the metatarsi injected with Ad-BMP-2 or Ad-BMP-6. Peak torque to failure and torsional stiffness were greater in osteotomies treated with Ad-BMP-2 than Ad-B...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society April 7, 2007 Volume 25, Issue 8 1094-1105 doi: 10.1002/jor.20375

Olstad K, Ytrehus B, Ekman S, Carlson CS, Dolvik NI.Material available for research into osteochondrosis (OC) in humans tends to represent chronic lesions. Comparative studies of early lesions in young animals are, therefore, important in clarifying the pathogenesis of OC in humans. Recent studies in pigs provide strong evidence that lesions of articular OC are associated with a focal failure in the cartilage canal vascular supply to epiphyseal growth cartilage (articular-epiphyseal cartilage complex excluding the articular cartilage). The purpose of the present study was to examine histological sections from a specific predilection site for ar...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society December 21, 2004 Volume 23, Issue 3 602-610 doi: 10.1016/j.orthres.2004.10.003

Céleste C, Ionescu M, Robin Poole A, Laverty S.Although intraarticular (IA) corticosteroids are frequently used to treat joint disease, the effects of their repeated use on articular cartilage remains controversial. The aim of our study was to determine the effects of a clinically recommended dose of IA triamcinolone acetonide (TA), on synovial fluid (SF) biomarkers of cartilage metabolism. Ten adult horses, free of osteoarthritis (OA) in their radiocarpal joints, were studied. One radiocarpal joint of each horse was randomly chosen for treatment and the contralateral anatomically paired joint acted as the control. Aseptic arthrocentesis w...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society September 19, 2014 Volume 33, Issue 1 63-70 doi: 10.1002/jor.22740

Chevrier A, Kouao AS, Picard G, Hurtig MB, Buschmann MD.Microfracture repair tissue in young adult humans and in rabbit trochlea is frequently of higher quality than in corresponding ovine or horse models or in the rabbit medial femoral condyle (MFC). This may be related to differences in subchondral properties since repair is initiated from the bone. We tested the hypothesis that subchondral bone from rabbit trochlea and the human MFC are structurally similar. Trochlea and MFC samples from rabbit, sheep, and horse were micro-CT scanned and histoprocessed. Samples were also collected from normal and lesional areas of human MFC. The subchondral bone...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society September 1, 1993 Volume 11, Issue 5 664-670 doi: 10.1002/jor.1100110508

Canè V, Botti P, Soana S.The influence of pulsed low-frequency electromagnetic fields (PEMFs) on bone formation was investigated in studies of the healing process of transcortical holes, bored at the diaphyseal region of metacarpal bones of six adult horses, exposed for 30 days to PEMFs (28 G peak amplitude, 1.3 ms rise time, and 75 Hz repetition rate). A pair of Helmholtz coils, continuously powered by a pulse generator, was applied for 30 days to the left metacarpal bone, through which two holes, of equal diameter and depth, had been bored at the diaphyseal region. Two equal holes, bored at the same level in the rig...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society February 11, 2011 Volume 29, Issue 7 1121-1130 doi: 10.1002/jor.21366

Nixon AJ, Begum L, Mohammed HO, Huibregtse B, O'Callaghan MM, Matthews GL.Autologous chondrocyte implantation (ACI) has been used clinically for over 15 years and yet definitive evidence of chondrocyte persistence and direct impact on cartilage repair in full-thickness lesions is scant and no data are available on ACI in partial-thickness defects in any animal model. This study assessed the effect of chondrocytes secured using periosteal overlay in partial- and full-thickness cartilage defects in the equine model. Paired cartilage defects 15 mm in diameter were made in the patellofemoral joint of 16 horse and repaired with ACI or periosteal flap alone. Response wa...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society March 4, 2006 Volume 24, Issue 4 725-732 doi: 10.1002/jor.20111

Huser CA, Davies ME.The objective of this study was the development and characterization of an in vitro model of the initiation of traumatic osteoarthritis (OA). Articular cartilage was obtained from seven healthy horses and from four horses diagnosed with OA. Cartilage disks were subjected to a single-impact load (500 g from 25, 50, or 100 mm) using a simple drop-tower device and cultured in vitro for up to 20 days. Cartilage sections were examined histologically to observe surface damage and proteoglycan loss. Percentage cell death was determined using TUNEL, release of glycosaminoglycans (GAG) to the medium wa...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society April 7, 2016 Volume 34, Issue 12 2162-2171 doi: 10.1002/jor.23251

Durgam SS, Stewart AA, Sivaguru M, Wagoner Johnson AJ, Stewart MC.Tendinitis is a common and a performance-limiting injury in athletes. This study describes the value of intralesional tendon-derived progenitor cell (TDPC) injections in equine flexor tendinitis. Collagenase-induced tendinitis was created in both front superficial digital flexor (SDF) tendons. Four weeks later, the forelimb tendon lesions were treated with 1 × 10 autogenous TDPCs or saline. Tendinitis was also induced by collagenase in one hind SDF tendon, to study the survival and distribution of DiI-labeled TDPCs 1, 2, 4, and 6 weeks after injection. The remaining normal tendon was used...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society September 25, 2009 Volume 28, Issue 3 403-411 doi: 10.1002/jor.20978

Ishihara A, Zekas LJ, Litsky AS, Weisbrode SE, Bertone AL.This study evaluated healing of equine metacarpal/metatarsal osteotomies in response to percutaneous injection of autologous dermal fibroblasts (DFbs) genetically engineered to secrete bone morphogenetic protein-2 (BMP2) or demonstrate green fluorescent protein (GFP) gene expression administered 14 days after surgery. Radiographic assessment of bone formation indicated greater and earlier healing of bone defects treated with DFb with BMP2 gene augmentation. Quantitative computed tomography and biomechanical testing revealed greater mineralized callus and torsional strength of DFb-BMP2-treated ...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society August 24, 2001 Volume 19, Issue 4 688-695 doi: 10.1016/S0736-0266(00)00060-7

Fubini SL, Todhunter RJ, Burton-Wurster N, Vernier-Singer M, MacLeod JN.Experimental evidence suggests that recommended dosages of some corticosteroids used clinically as antiinflammatory agents for treating arthropathies damage articular cartilage, but low dosages may be chondroprotective. The purpose of this study was to evaluate how different concentrations of methylprednisolone affect chondrocyte function and viability. Articular cartilage and chondrocytes were obtained from young adult horses, 1.5-3.5 years of age. Corticosteroid-induced changes in collagen expression were studied at the transcriptional level by Northern blot analyses and at the translational...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society January 10, 2002 Volume 19, Issue 6 1035-1042 doi: 10.1016/S0736-0266(01)00027-4

Murray RC, Vedi S, Birch HL, Lakhani KH, Goodship AE.It was hypothesised that subchondral bone thickness, hardness and remodelling are influenced by exercise intensity, and by location within a joint. Dorsal carpal osteochondral injury is a major cause of lameness in horses undergoing high intensity training. This project aimed to determine the subchondral bone thickness, formation, resorption and hardness at sites with high and low incidence of pathology in 2 year-old horses undergoing 19 weeks high intensity treadmill training or low intensity exercise, and to compare these factors between exercise groups. Dorsal and palmar test sites were ide...

Journal of orthopaedic research : official publication of the Orthopaedic Research Society September 20, 2001 Volume 19, Issue 5 919-926 doi: 10.1016/S0736-0266(01)00009-2

Taylor D, Kuiper JH.This paper addresses an anomaly which exists in the current literature regarding stress fractures. Analysis of the data on fatigue strength of bone samples in vitro would conclude that these fractures should never occur at the strain levels known to occur in vivo. This anomaly can be resolved by including in the analysis the effect of stressed volume, whereby larger volumes of material are expected to have worse fatigue properties. A Weibull analysis was used to predict the probability of failure, Pf; this was an upper-bound prediction because it did not include the effects of remodelling and ...

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NLM ID:	8404726
(DNLM):	J33365000(s)
(OCoLC):	09069401
Coden:	JOREDR
LCCN:	sn 82008603
Classification:	W1 JO804SF

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