A cost-effective cell- and matrix-based minimally invasive single-stage chondroregenerative technique developed with validated vertical translation methodology

Abstract

Introduction The morbidity and significant health economic impact associated with the chondral lesion has led to a large number of strategies for therapeutic neochondrogenesis. The challenge has been to develop techniques that are cost effective single-stage procedures with minimal surgical trauma that have undergone rigorous preclinical scrutiny and robust reproducible assessment of effectiveness. A biological repair requires the generation of a cellular and matrix composite with appropriate signalling for chondrogenic differentiation. Methods and results A technique was developed that allowed chondrogenic primary (uncultured) cells from bone marrow aspirate concentrate, combined with a composite hydrophilic and fibrillar matrix to be applied arthroscopically to a site of a chondral lesion. The construct was tested in vitro and in animal experiments before clinical trials. Clinical trials involved 60 patients in a prospective study. Symptomatic International Cartilage Repair Society grade 3 and 4a lesions were mapped and treated. Pre- and postoperative clinical assessments showed statistically significant improved outcomes; Lysholm Knee Scoring Scale (mean 52.8 to > 76.4; P < 0.05) International Knee Documentation Committee (mean 39 to > 79 P < 0.05) and Knee injury and Osteoarthritis Outcome Score (64.5 to >89.2 P < 0.05). Postoperative magnetic resonance imaging was evaluated morphologically (magnetic resonance observation of cartilage repair tissue, average MOCART score 72) and qualitatively; the regenerate was comparable to native cartilage. Conclusions This technique is effective, affordable, requires no complex tools and delivers a single-stage treatment that is potentially accessible to any centre capable of performing arthroscopic surgery. Good clinical results were found to be sustained at five years of follow-up with a regenerate that appears hyaline like using multiple magnetic resonance measures.

<p>Clinical Applicability of Adult Human Mesenchymal Stem Cell Therapy in the Treatment of Knee Osteoarthritis</p>

“…Further studies are being conducted to better understand the impact of MCIC on larger cartilage defects. 12,25 Although the improvement observed in most trials did not demonstrate statistical significance, the overall impact of treatments utilizing MSCs indicates an improvement in all KOOS subscales, especially in pain reduction and function.…”

“…Larger sample size required to better understand the efficacy of BM-MSCs therapy in KOA. Shetty A. et al 25 60 (Age 19–61) Prospective phase I open-label clinical trial MCIC- Arthroscopic procedure utilizing CO2 insufflation. Postoperative clinical assessments demonstrated significant improvement of P < 0.05 in KOOS, LKSS and IKDC.…”

“…Further studies are being conducted to better understand the impact of MCIC on larger cartilage defects. 12 , 25 …”

Cell therapy for cartilage repair

“…However, of all the nucleated cells found within BMA, only ∼0.001–0.01% of these are actually MSCs [ 36 ]. This percentage can be increased by centrifugation of the aspirate, producing ‘bone-marrow aspirate concentrate’ (BMAC) which is also believed to be rich in growth factors and cytokines [ 62 , 63 ]. Thus autologous BMAC can be prepared in the operating theatre and implanted into a chondral or osteochondral defect in a single-stage procedure, often in combination with a scaffold, e.g.…”

Osteoartrite de joelho e o aspirado de medula óssea como escolha de tratamento - Uma revisão narrativa

“…Um estudo prospectivo de 5 anos, feito com 60 pacientes, com idade média de 44 anos, escolhidos randomicamente, fez a coleta na crista ilíaca (sem preferência entre porção anterior ou posterior), aplicou BMAC via artroscopia, e avaliou esses participantes em diversos intervalos durante o período de pesquisa, utilizando escores funcionais e ressonâncias magnéticas para verificar a evolução de cada um. Ficou evidenciado um pico de melhora nos primeiros seis meses, com leve evolução até dois anos de acompanhamento, e estabilizando, sem muita melhora, até o quinto ano de estudo (Shetty et al, 2018).…”