Autologous chondrocyte implantation drives early chondrogenesis and organized repair in extensive full‐ and partial‐thickness cartilage defects in an equine model

Abstract

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 was assessed at 8 weeks by clinical, microradiographic, and histologic appearance, and by collagen type II immunohistochemistry, and proteoglycan and DNA quantification. ACI improved histologic scores in partial-and full-thickness cartilage defects, including defect filling, attachment to the underlying subchondral bone, and presence of residual chondrocyte accumulations. For partial-thickness defects chondrocyte predominance, collagen type II content, and toluidine stained matrix were enhanced, and attachment to the surrounding cartilage improved. DNA and PG content of grafted partial-thickness defects was improved by chondrocyte implantation. Periosteal patches alone did not induce cartilage repair. This study indicated implantation of chondrocytes to cartilage defects improved healing with a combination of persisting chondrocyte regions, enhanced collagen type II formation, and better overall cartilage healing scores. Use of ACI in the more challenging partial-thickness defects also improved histologic indices and biochemical content. The equine model of cartilage healing closely resembles cartilage repair in man, and results of this study confirm cell persistence and improved early cartilage healing events after ACI. ß

Maturation-dependent spontaneous healing of partial thickness cartilage defects in infantile rats

“…Autologous chondrocyte implantation, which is a known treatment option for FTCDs, promotes PTCD repair in equines (Nixon et al 2011). MSC introduction into PTCD lesions enhances cartilage repair (Mrugala et al 2008).…”

Cell-based Therapies for Equine Joint Disease

“…[28][29][30] There are problems associated with the need for two procedures, donor site morbidity, chondrocyte phenotypic instability, and scaffold/patch delamination, but ACI is particularly applicable for larger (>4 cm 2 ) femoral condylar lesions in young adults with minimal degenerative changes in the affected joint. 31 ACI has been shown effective for both short-term and long-term repair of large partial-thickness and full-thickness articular cartilage defects in horses 32,33 ; however, the complexity of the initial cartilage collection, ex vivo expansion, and surgical reimplantation makes this approach unfeasible for the majority of equine surgical practices. A 2009 study by Frisbie and colleagues 19 also assessed the clinical utility of autologous cartilage fragment implantation for cartilage defect repair.…”

Evaluation of biomarkers following autologous osteochondral transplantation in the equine stifle joint — An experimental study

“…The most frequent lesions involve fissures, fibrillation or ulceration of the surface or subchondral bone cysts (SBC) at that location. In both human and equine patients, focal cartilaginous lesions can originate from chondropathy or chondral trauma and are difficult to treat and manage, especially on weight-bearing joint surfaces (Hangody et al, 2010;Nixon et al, 2011). When such lesions are left untreated, the biomechanical protective function of cartilage declines, subsequently leading to a loss of joint function (Buckwalter and Mankin, 1998) and predisposing the joint to the development of osteoarthritis (OA) (Malda et al, 2012).…”

“…Substance P is associated with clinically detectable joint pain in the horse (de Grauw et al, 2006). Several methods have been described in the equine literature to evaluate outcome measures of different articular resurfacing techniques, including postoperative clinical assessment, long-term follow-up with owner questionnaires, radiological follow-up of the affected joints, follow-up arthroscopies, and anteor postmortem histological evaluation of the transplanted area (Kold and Hickman, 1984;Howard et al, 1995;Bodó et al, 2000;Jackson et al, 2000;Hurtig et al, 2001;Sandler et al, 2002;Bodó et al, 2004;Wallis et al, 2008;Janicek et al, 2010;Nixon et al, 2011;Ortved et al, 2011;Malda et al, 2012;Bodó et al, 2014;Santschi et al, 2015). However, to the best of the authors' knowledge, no data are available on the evaluation of synovial biomarkers and basic parameters following AOT in humans or horses.…”