Repair of avascular meniscal injuries using juvenile meniscal fragments: An in vitro organ culture study

Dai, Zhu; Li, Kanghua; Chen, Zhiwei; Liao, Ying; Yang, Le-zhong; Ding, Wenjun

doi:10.1002/jor.22405

Cited by 12 publications

(16 citation statements)

References 22 publications

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“…Combination of dynamic loading and IL-1 enhanced integrative meniscal repair in an explant culture model 10 . Juvenile meniscus fragments implanted in avascular defects enhanced meniscus healing in vitro 11 . More recently, tissue engineering approaches have been applied for meniscus repair and healing 12 .…”

Section: Introductionmentioning

confidence: 97%

Engineered Healing of Avascular Meniscus Tears by Stem Cell Recruitment

Tarafder

Gulko

Sim

et al. 2018

Sci Rep

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Meniscus injuries are extremely common with approximately one million patients undergoing surgical treatment annually in the U.S. alone. Upon injury, the outer zone of the meniscus can be repaired and expected to functionally heal but tears in the inner avascular region are unlikely to heal. To date, no regenerative therapy has been proven successful for consistently promoting healing in inner-zone meniscus tears. Here, we show that controlled applications of connective tissue growth factor (CTGF) and transforming growth factor beta 3 (TGFβ3) can induce seamless healing of avascular meniscus tears by inducing recruitment and step-wise differentiation of synovial mesenchymal stem/progenitor cells (syMSCs). A short-term release of CTGF, a selected chemotactic and profibrogenic cue, successfully recruited syMSCs into the incision site and formed an integrated fibrous matrix. Sustain-released TGFβ3 then led to a remodeling of the intermediate fibrous matrix into fibrocartilaginous matrix, fully integrating incised meniscal tissues with improved functional properties. Our data may represent a novel clinically relevant strategy to improve healing of avascular meniscus tears by recruiting endogenous stem/progenitor cells.

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Section: Introductionmentioning

confidence: 97%

Engineered Healing of Avascular Meniscus Tears by Stem Cell Recruitment

Tarafder

Gulko

Sim

et al. 2018

Sci Rep

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“…Organ culture has been employed in studies of meniscal tissue (Dai et al, 2013;Narita et al, 2009), articular cartilage (Jacoby andJayson, 1976;Hollander et al, 1991;Fay et al, 2006;Tchetina et al, 2006), OC explants (Amin et al, 2009a;Seol et al, 2014), and whole porcine patellae (Ashwell et al, 2008;Ashwell et al, 2013). However, organ culture is extremely challenging, as conditions in these cultures must be able to maintain tissue viability and stable matrix composition.…”

Section: Introductionmentioning

confidence: 99%

“…Monitoring of osteochondral organ culture fluorescein diacetate and PI have been shown to be useful for monitoring cell viability, by labelling live and dead cells in tissues or engineered tissues, and localising them using confocal microscopy, but this is limited to tissues up to 4 mm in thickness (Amin et al, 2009b;Dai et al, 2013;Breuls et al, 2003). MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and XTT (2,3-bis-[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide tetrazolium salt) reduction assays, which measure cellular oxidative metabolism, also provide an accurate measure of tissue metabolism, but the process requires the destruction of the tissue (Mosmann, 1983;Roehm et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

“…Other methods of viability assessment include the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) apoptosis assay (Mueller-Rath et al, 2007;Narita et al, 2009;Seol et al, 2014), and histological analysis of cells and extracellular matrix (ECM) (Naqvi et al, 2005;Mueller-Rath et al, 2007;Dai et al, 2013), but these techniques require the tissues to be fixed and sectioned prior to the assay protocols. Apoptosis can also be assessed by measuring caspase 3/7 in whole tissue lysates, but again this requires destruction of the tissue (Dudli et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Non-destructive monitoring of viability in an ex vivo organ culture model of osteochondral tissue

Elson

Fox²,

Tipper³

et al. 2015

eCM

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Organ culture is an increasingly important tool in research, with advantages over monolayer cell culture due to the inherent natural environment of tissues. Successful organ cultures must retain cell viability. The aim of this study was to produce viable and non-viable osteochondral organ cultures, to assess the accumulation of soluble markers in the conditioned medium for predicting tissue viability. Porcine femoral osteochondral plugs were cultured for 20 days, with the addition of Triton X-100 on day 6 (to induce necrosis), camptothecin (to induce apoptosis) or no toxic additives. Tissue viability was assessed by the tissue destructive XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide tetrazolium salt) assay method and LIVE/DEAD ® staining of the cartilage at days 0, 6 and 20. Tissue structure was assessed by histological evaluation using haematoxylin & eosin and safranin O. Conditioned medium was assessed every 3-4 days for glucose depletion, and levels of lactate dehydrogenase (LDH), alkaline phosphatase (AP), glycosaminoglycans (GAGs), and matrix metalloproteinase (MMP)-2 and MMP-9. Necrotic cultures immediately showed a reduction in glucose consumption, and an immediate increase in LDH, GAG, MMP-2 and MMP-9 levels. Apoptotic cultures showed a delayed reduction in glucose consumption and delayed increase in LDH, a small rise in MMP-2 and MMP-9, but no significant effect on GAGs released into the conditioned medium. The data showed that tissue viability could be monitored by assessing the conditioned medium for the aforementioned markers, negating the need for tissue destructive assays. Physiologically relevant whole-or part-joint organ culture models, necessary for research and pre-clinical assessment of therapies, could be monitored this way, reducing the need to sacrifice tissues to determine viability, and hence reducing the sample numbers necessary.

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“…PLGA mesh and fibre reinforced collagen-GAG scaffolds seeded with chondrocytes [180] or meniscal cells [168] supplemented with PRP have been evaluated for meniscal repair. Minced juvenile menisci sandwiched with meniscal explants from inner meniscal regions have been evaluated for their reparative potential on tears of the inner meniscal regions [181]. A number of bioactive factors have been evaluated for their reparative properties on meniscal defects.…”

Section: Bioscaffolds Bioactive Substances and Bioadhesives And Menimentioning

confidence: 99%

Novel Approaches in Meniscal Repair Utilizing Mesenchymal Stem Cells, New Generation Bioscaffolds and Biological Adhesives as Cell Delivery Vehicles

Melrose¹

2019

Meniscus of the Knee - Function, Pathology and Management

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Mesenchymal stem cells (MSCs) have been widely applied in the repair of the knee-joint menisci which have a limited ability to undergo spontaneous repair. The menisci stabilise the knee-joint and are weight-bearing structures subjected to considerable tensional and compressive forces during flexion-extension and torsional loading of the knee. Traumatic loading of the knee-joint menisci can generate a number of lesions in the inner avascular meniscal regions. These have a limited capability of intrinsic repair and predispose the underlying articular cartilages to premature osteoarthritis. A number of strategies have therefore been developed for meniscal repair employing MSCs, bioscaffolds, hydrogels, biological glue cell delivery systems and agents which promote cell proliferation/matrix synthesis. Meniscal implants have also been developed in combination with the above procedures. It is important that meniscal defects be repaired not only to maintain kneejoint stability but also to prevent further degenerative changes in other knee joint tissues. Degenerative menisci contribute degradative proteinases and inflammatory mediators to the total synovial degradative proteinase pool. Partial or total surgical removal of the menisci is not a solution since this leads to premature osteoarthritis. Meniscal integrity needs to be maintained or repair strategies implemented in a timely manner to maintain knee joint function.

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Repair of avascular meniscal injuries using juvenile meniscal fragments: An in vitro organ culture study

Cited by 12 publications

References 22 publications

Engineered Healing of Avascular Meniscus Tears by Stem Cell Recruitment

Engineered Healing of Avascular Meniscus Tears by Stem Cell Recruitment

Non-destructive monitoring of viability in an ex vivo organ culture model of osteochondral tissue

Novel Approaches in Meniscal Repair Utilizing Mesenchymal Stem Cells, New Generation Bioscaffolds and Biological Adhesives as Cell Delivery Vehicles

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