Allogeneic chondrocyte implantation: What is stopping it from being a standard of care?

Ibrahim, Sufyan; Nagesh, Himanshu Yashavanthi; Pandey, Vivek

doi:10.25259/jassm_8_2021

Cited by 6 publications

(2 citation statements)

References 36 publications

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“…Furthermore, besides the high viability of cells in young donors, there is strong evidence regarding the enhanced chondrogenic potential of juvenile chondrocytes versus adult chondrocytes. Data also suggest that juvenile chondrocytes may not be immunogenic in adult hosts, supporting the possibility that such cells may be used as allografts for cartilage regeneration in vivo (Adkisson et al 2010;Ibrahim et al 2021). In addition, use of young articular chondrocytes derived from allogeneic cadavers eliminates donor-site morbidity, the requirement for two surgical procedures associated with the therapeutic application of autologous chondrocyte implantation, and finally our work seeks to generate knowledge about the correct selection of allogeneic chondrocyte donors, and is aimed at providing knowledge to be useful for research groups that are working on the development of new techniques that are evolving from ACI.…”

Section: Discussionmentioning

confidence: 86%

Suitable characteristics in the selection of human allogeneic chondrocytes donors to increase the number of viable cells for cartilage repair

et al. 2023

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Autologous chondrocyte implantation has shown optimal long-term outcomes in the treatment of cartilage lesions. The challenge for a single-stage approach lies in obtaining sufficient number of cells with high viability. The answer could lie in supplementing or replacing them with allogenic chondrocytes coming from cadaveric donors. In the present work, we aimed to compare the number of viable cells isolated from cartilage of live and cadaveric donors and to determine the suitable characteristics of the best donors. A total of 65 samples from donors aged from 17 to 55 years, either women or men, were enrolled in this study (33 living vs. 32 cadaveric). The mean time of hours from death to processing samples in cadaveric donors was higher compared to live donors (64.3 ± 17.7 vs. 4.6±6.4). The number of isolated chondrocytes per gram of cartilage was higher in cadaveric donors (5.389 × 10 6 compared to 3.067 × 10 6 in living donors), whereas the average of cell viability was comparable in both groups (84.16% cadaveric, 87.8% alive). It is possible to obtain viable chondrocytes from cartilage harvested from cadaveric donors, reaching a similar cell number and viability to that obtained from the cartilage of living donors.

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Section: Discussionmentioning

confidence: 86%

Suitable characteristics in the selection of human allogeneic chondrocytes donors to increase the number of viable cells for cartilage repair

et al. 2023

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“… 25 , 26 However, it is recognized that the translation of these allogeneic therapies into clinical practice has been limited, likely due to difficulties in sourcing appropriate adult articular cartilage, growing sufficient numbers of cells under GMP conditions, and difficulties with preserving cells appropriately. 27 As part of developing allogeneic chondrocyte therapies, there is a need to optimize existing autologous chondrocyte manufacturing processes, particularly to grow large numbers of cells from a cartilage harvest biopsy, with standard ACI chondrocyte expansion on TCP for 2–3 weeks 6 , 28 unlikely to be capable of producing sufficient cell yields to treat more than a single patient.…”

Section: Discussionmentioning

confidence: 99%

The Upscale Manufacture of Chondrocytes for Allogeneic Cartilage Therapies

Hulme

Garcia

Mennan

et al. 2023

Tissue Engineering Part C: Methods

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Allogeneic chondrocyte therapies need to be developed to allow more individuals to be treated with a cell therapy for cartilage repair and to reduce the burden and cost of the current two-stage autologous procedures. Upscale manufacture of chondrocytes using a bioreactor could help provide an off-the-shelf allogeneic chondrocyte therapy with many doses being produced in a single manufacturing run. In this study, we assess a good manufacturing practice-compliant hollow-fiber bioreactor (Quantum ® ) for adult chondrocyte manufacture. Chondrocytes were isolated from knee arthroplasty-derived cartilage ( n = 5) and expanded in media supplemented with 10% fetal bovine serum (FBS) or 5% human platelet lysate (hPL) on tissue culture plastic (TCP) for a single passage. hPL-supplemented cultures were then expanded in the Quantum bioreactor for a further passage. Matched, parallel cultures in hPL or FBS were maintained on TCP. Chondrocytes from all culture conditions were characterized in terms of growth kinetics, morphology, immunoprofile, chondrogenic potential (chondrocyte pellet assays), and single telomere length analysis. Quantum expansion of chondrocytes resulted in 86.4 ± 38.5 × 10 6 cells in 8.4 ± 1.5 days, following seeding of 10.2 ± 3.6 × 10 6 cells. This related to 3.0 ± 1.0 population doublings in the Quantum bioreactor, compared with 2.1 ± 0.6 and 1.3 ± 1.0 on TCP in hPL- and FBS-supplemented media, respectively. Quantum- and TCP-expanded cultures retained equivalent chondropotency and mesenchymal stromal cell marker immunoprofiles, with only the integrin marker, CD49a, decreasing following Quantum expansion. Quantum-expanded chondrocytes demonstrated equivalent chondrogenic potential (as assessed by ability to form and maintain chondrogenic pellets) with matched hPL TCP populations. hPL manufacture, however, led to reduced chondrogenic potential and increased cell surface positivity of integrins CD49b, CD49c, and CD51/61 compared with FBS cultures. Quantum expansion of chondrocytes did not result in shortened 17p telomere length when compared with matched TCP cultures. This study demonstrates that large numbers of adult chondrocytes can be manufactured in the Quantum hollow-fiber bioreactor. This rapid, upscale expansion does not alter chondrocyte phenotype when compared with matched TCP expansion. Therefore, the Quantum provides an attractive method of manufacturing chondrocytes for clinical use. Media supplementation with hPL for chondrocyte expansion may, however, be unfavorable in terms of retaining chondrogenic capacity. Impact statement This is the first study, to our knowledge, to manufacture adult chondrocytes in a good manufacturing practice-compliant hollow-fiber bioreactor (Quantum ® ). We provide evidence that chondrocytes can be manufactured using this methodology while retaining comparable properties to chondrocytes expanded in matched tissue cul...

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Low‐density cultured cartilage cells expanded in platelet lysate present distinct features to develop an innovative clinical treatment for diffuse cartilage lesions

Colombini,

Lopa,

Libonati

et al. 2024

Knee surg. sports traumatol. arthrosc.

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PurposeChondrocyte‐based cell therapies are effective for the treatment of chondral lesions, but remain poorly indicated for diffuse lesions in the context of early osteoarthritis (OA). The aim of this study was to develop a protocol to obtain chondroprogenitor cells suitable for the treatment of diffuse chondral lesions within early OA.MethodsCartilage cells were expanded at low density in human platelet lysate (hPL). A test was performed to exclude senescence. The expression of surface cluster of differentiation 146, cluster of differentiation 166, major histocompatibility complex (MHC)‐I and MHC‐II and of genes of interest were evaluated, as well as the trophic potential of these cells, by the assessment of lubricin and matrix production. The immunomodulatory potential was assessed through their co‐culture with macrophages.ResultsCartilage cells expanded at low density in hPL showed higher proliferation rate than standard‐density cells, no replicative senescence, low immunogenicity and expression of lubricin. Moreover, they presented an increased expression of chondrogenic and antihypertrophic markers, as well as a superior matrix deposition if compared to cells cultured at standard density. Cartilage cells induced on macrophages an upregulation of CD206, although a higher increase of CD163 expression was observed in the presence of low‐density cells.ConclusionsThese findings lay the grounds to explore the clinical usefulness of low‐density cultured cartilage cells to treat diffuse lesions in early OA joints for both autologous and allogenic use.Level of EvidenceNot applicable.

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Allogeneic chondrocyte implantation: What is stopping it from being a standard of care?

Cited by 6 publications

References 36 publications

Suitable characteristics in the selection of human allogeneic chondrocytes donors to increase the number of viable cells for cartilage repair

Suitable characteristics in the selection of human allogeneic chondrocytes donors to increase the number of viable cells for cartilage repair

The Upscale Manufacture of Chondrocytes for Allogeneic Cartilage Therapies

Low‐density cultured cartilage cells expanded in platelet lysate present distinct features to develop an innovative clinical treatment for diffuse cartilage lesions

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