Particulated Cartilage for Chondral and Osteochondral Repair: A Review

Christensen, Bjørn Borsøe; Olesen, Morten Lykke; Hede, Kris Chadwick; Bergholt, Natasja Leth; Foldager, Casper Bindzus; Lind, Martin

doi:10.1177/1947603520904757

Cited by 42 publications

(38 citation statements)

References 54 publications

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“…Clinical experience was still limited, with short-term studies demonstrating the procedure to be safe, feasible, and effective, including improvements in subjective patient scores and MRI evidence of good defect fill, but a randomized trial and long-term follow-up are lacking. 6…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…So far, about 10,000 people have received PJAC surgery worldwide, and the long-term clinical effects of PJAC surgery have been confirmed. 10,13,15,16,17,29,37 In 2013, Tompkins et al 37 applied the PJAC technique to treat 16 patients with patellar cartilage disease. After 28 months, the patients’ International Knee Documentation Committee (IKDC) scores had improved significantly, and 89% and 73% of the patients’ MRI results showed normal or near-normal cartilage repair, respectively, at the repaired defect area.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…In recent years, it has been found that the long-term treatment efficacy of microfractures is not good, and the proliferative capacity of PJAC is stronger than that of adult cells, which creates a promising treatment plan. 10 Although the application of PJAC has achieved some effects on the repair of cartilage defects, whether the donor cells participate in the process of cartilage defect repair from a histological perspective still needs to be analyzed. To explore the mechanism of PJAC repair, we chose minipigs as a large animal model to simulate the cartilage transplant process of PJAC.…”

Section: Discussionmentioning

confidence: 99%

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Donor Cell Fate in Particulated Juvenile Allograft Cartilage for the Repair of Articular Cartilage Defects

Zhang

Cao

et al. 2020

Am J Sports Med

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Background: Particulated juvenile allograft cartilage (PJAC) has demonstrated good clinical efficacy in repairing articular cartilage defects, but the related repair mechanism after transplant and the biological characteristics of the transplanted cells are still unclear. Purpose: To study the efficacy of PJAC in repairing full-thickness cartilage defects and the specific fate of donor cells to provide experimental evidence for its clinical application. Study Design: Controlled laboratory study. Methods: Twenty female Guizhou minipigs were randomly divided into an experimental group and a control group. An 8-mm cylindrical full-thickness cartilage defect was created in the femoral trochlea of 1 knee in all minipigs. The experimental group received transplant of PJAC from 5 male juvenile Guizhou minipigs (PJAC group; n = 10) and the control group received autologous cartilage chips (ACC group; n = 10). Follow-up assessments were conducted at 1 month and 3 months to track the transplanted cells by the male-specific sex-determining region Y-linked (SRY) gene; tissue sections were hybridized in situ, and O’Driscoll histological scoring was performed according to hematoxylin and eosin staining, safranin O and fast green staining, and toluidine blue O staining, as well as immunohistochemical evaluation of aggrecan and Sry-type HMG-box 9 (SOX9). Results: All 20 Guizhou minipigs were followed; no infection or incision healing disorder occurred after the operation. By SRY in situ hybridization, the SRY signal of the transplanted cells was positive in the repaired tissue of the defect, and the SRY positive signal could still be detected in repaired tissue at 3 months postoperatively. The average number of positive cells was 68.6 ± 11.91 at 1 month and 32.6 ± 3.03 at 3 months (confocal microscope: ×400), and the difference was statistically significant. The O’Driscoll histological scores were 14 ± 0.71 in the ACC group and 9.8 ± 0.84 in the PJAC group at 1 month, and 18 ± 1.20 in the ACC group and 17.4 ± 1.14 in the PJAC group at 3 months. The scores were statistically significant between the ACC group and PJAC group at 1 month. The positive rates of SOX9 in the PJAC and ACC groups at 1 month were 67.6% ± 3.78% and 63.4% ± 5.30%, respectively, and the difference was not statistically significant ( P > .05). The positive rates of SOX9 in the PJAC and ACC groups at 3 months were 68.8% ± 2.69% and 17.1% ± 1.26%, respectively, and the difference was statistically significant ( P < .05). The positive rates of aggrecan in the PJAC and ACC groups at 1 month were 40.5% ± 2.78% and 42.4% ± 0.54% respectively, and the difference was not statistically significant ( P > .05). The positive rates of aggrecan in the PJAC and ACC groups at 3 months were 40.8% ± 1.50% and 30.1% ± 2.44%, respectively, and the difference was not statistically significant ( P > .05). Conclusion: An animal model was established with Guizhou minipigs, and the cartilage defect was repaired with PJAC from male minipigs. The SRY gene positive signal could be detected from the repaired tissue by in situ hybridization, indicating that the transplanted cells survived at least 3 months. The key genes of cartilage formation, SOX9 and aggrecan, were expressed at 1 month and 3 months, and SOX9 expression was stronger in the PJAC group than the ACC group at 3 months. Clinical Relevance: This study suggests that it is feasible to study the biological characteristics of transplanted cells in the cartilage region by the sex-determining gene.

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“…Based on the characteristics of strong proliferation of transplanted juvenile cartilage, particulated juvenile allograft cartilage (PJAC) from donors under 13 years old is prepared and stored at low temperature, and then applied with brin glue to the cartilage defects [9]. At present, DeNovo NT, a commercial product of PJAC, has been widely used in clinical practice and has achieved satisfactory therapeutic effects [10][11][12][13][14][15]. Compared with microfractures and ACC, PJAC transplantation has better long-term e cacy.…”

Section: Introductionmentioning

confidence: 99%

Proliferation Ability of Particulated Juvenile Allograft Cartilage

Zhang

Zhao

et al. 2020

Preprint

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Background: Particulated juvenile allograft cartilage (PJAC) has a good short-term clinical efficacy in repairing articular cartilage defects, but the proliferation ability of PJAC and the biological characteristics of transplanted cells after transplantation are still unclear.Purpose: To study the cartilage proliferation ability of PJAC in repairing full-thickness cartilage defects and the reasons for proliferation to provide experimental evidence for its clinical application.Study Design: Controlled laboratory study.Methods: Twenty Guizhou minipigs were randomly divided into the Autologous cartilage chip transplantation (PJAC) group and Autologous cartilage chip transplantation (ACC) group. In all minipigs, an 8 mm cylindrical full-thickness cartilage defect was created in the femoral trochlea of one knee. The experimental group received PJAC transplantation from five juvenile donor of Guizhou minipigs (PJAC group; n = 10) and the control group received transplantation of autologous cartilage chips (ACC group; n = 10). Both groups were followed at 1, 3 months after surgery; immunohistochemical evaluation of the tissue sections Ki-67, Lin28 was conducted, the positive rate was calculated according to the staining, and the proliferation ability of PJAC was analyzed. Results: All 20 Guizhou minipigs were followed, and there was no infection or incision healing disorder after surgery. By Ki-67 and Lin28 immunohistochemistry, the positive rates of Ki-67 were (88.9±0.2)% in the PJAC group and (28.3±3.6)% in the ACC group at 1 month, and the difference was statistically significant (P<0.05); the positive rates of Lin28 were (34.6±3.3)% in the PJAC group and (7.6±1.4)% in the ACC group at 1 month, and the difference was statistically significant (P<0.05). At 3 months, the positive rates of Ki-67 in PJAC group and ACC group were (53.6±6.9）% and (1.97±0.3%), respectively (P<0.05 ) and the positive rates of Lin28 were (86.6±3.3%) and (1.4±0.3%) , respectively (P<0.01 ).Conclusion: A large animal model was established with Guizhou minipigs and the expression of Ki-67 protein and Lin28 protein in the repaired transplanted tissue was detected by immunohistochemistry was stronger than that of adult cartilage. The proliferation of PJAC within 3 months after 3 months of transplantation was stronger than adult cartilage. The enhanced expression of Lin28 may be one of the mechanisms by which PJAC achieved stronger proliferation ability than adult cartilage.PJAC technology has shown good application prospects for repairing cartilage defects.

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Particulated Cartilage for Chondral and Osteochondral Repair: A Review

Cited by 42 publications

References 54 publications

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

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

Donor Cell Fate in Particulated Juvenile Allograft Cartilage for the Repair of Articular Cartilage Defects

Proliferation Ability of Particulated Juvenile Allograft Cartilage

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