Five-Year Outcome of 1-Stage Cell-Based Cartilage Repair Using Recycled Autologous Chondrons and Allogenic Mesenchymal Stromal Cells: A First-in-Human Clinical Trial

Abstract

Background: Long-term clinical evaluation of patient outcomes can steer treatment choices and further research for cartilage repair. Using mesenchymal stromal cells (MSCs) as signaling cells instead of stem cells is a novel approach in the field. Purpose: To report the 5-year follow-up of safety, clinical efficacy, and durability after treatment of symptomatic cartilage defects in the knee with allogenic MSCs mixed with recycled autologous chondrons in first-in-human study of 1-stage cartilage repair. Study Design: Case series; Level of evidence, 4. Methods: This study is an investigator-driven study aiming at the feasibility and safety of this innovative cartilage repair procedure. Between 2013 and 2014, a total of 35 patients (mean ± SD age, 36 ± 8 years) were treated with a 1-stage cartilage repair procedure called IMPACT (Instant MSC Product Accompanying Autologous Chondron Transplantation) for a symptomatic cartilage defect on the femoral condyle or trochlear groove. Subsequent follow-up after initial publication was performed annually using online patient-reported outcome measures with a mean follow-up of 61 months (range, 56-71 months). Patient-reported outcome measures included the KOOS (Knee injury and Osteoarthritis Outcome Score), visual analog scale for pain, and EuroQol–5 Dimensions. All clinical data and serious adverse events, including additional treatment received after IMPACT, were recorded. A failure of IMPACT was defined as a chondral defect of at least 20% of the index lesion with a need for a reintervention including a surgical procedure or an intra-articular injection. Results: Using allogenic MSCs, no signs of a foreign body response or serious adverse reactions were recorded after 5 years. The majority of patients showed statistically significant and clinically relevant improvement in the KOOS and all its subscales from baseline to 60 months: overall, 57.9 ± 16.3 to 78.9 ± 17.7 ( P < .001); Pain, 62.3 ± 18.9 to 79.9 ± 20.0 ( P = .03); Function, 61.6 ± 16.5 to 79.4 ± 17.3 ( P = .01); Activities of Daily Living, 69.0 ± 19.0 to 89.9 ± 14.9 ( P < .001); Sports and Recreation, 32.3 ± 22.6 to 57.5 ± 30.0 ( P = .02); and Quality of Life, 25.9 ± 12.9 to 55.8 ± 26.8 ( P < .001). The visual analog scale score for pain improved significantly from baseline (45.3 ± 23.6) to 60 months (15.4 ± 13.4) ( P < .001). Five cases required reintervention. Conclusion: This is the first study showing the midterm safety and efficacy of the proof of concept that allogenic MSCs augment 1-stage articular cartilage repair. The absence of serious adverse events and the clinical outcome support the longevity of this unique concept. These data support MSC-augmented chondron transplantation (IMPACT) as a safe 1-stage surgical solution that is considerably more cost-effective and a logistically advantageous alternative to conventional 2-stage cell-based therapy for articular chondral defects in the knee.

Human Mesenchymal Stromal Cells Enhance Cartilage Healing in a Murine Joint Surface Injury Model

“…hMSCs have already been used in knees of patients, for example hMSCs derived from bone marrow have been used and show promise in treating cartilage defects [48] and hMSCs from umbilical cord blood for treating medial knee OA [49]. However, both of these were used in conjunction with other therapeutics; the bone marrow MSCs were accompanied by applying autologous chondrons as well and the cord blood MSCs with high tibial osteotomies, such that it is difficult to know how the MSCs alone would have performed.…”

Cell therapy for cartilage repair

“…In this study, 35 patients were treated using autologous ‘chondrons’ and allogeneic MSCs in a fibrin glue carrier. The 5-year outcome data demonstrated that the majority of patients showed statistically significant and clinically relevant improvement in the KOOS and all its subscales from baseline [ 85 ]. The study protocol for a follow-on 60 patient randomised placebo-controlled IMPACT2 trial has now been outlined [ 86 ] and is currently recruiting ( http://clinicaltrials.gov : NCT04236739).…”

From Single Batch to Mass Production–Automated Platform Design Concept for a Phase II Clinical Trial Tissue Engineered Cartilage Product

“…In similar approaches from the food industry, decontamination and cleaning reagents would be sprayed across surfaces and devices to remove any potential residual cell material. The platform is further equipped with a spray nozzle that may be used by the dual arm robot to clean any unsprayed areas [2A, (10)]. Afterwards the surfaces are dried with sterilized compressed air.…”

“…Current treatments for focal cartilage defects, e.g., microfracturing or autologous articular chondrocyte implantation, are often associated with drawbacks such as limited defect sizes and donor site morbidity (7)(8)(9). Various new treatment approaches using ATMPs are currently under scientific investigation, also in clinical trials with mainly somatic cell therapy medicinal products (sCTMP) among others (10,11).…”