Repair of articular cartilage defect with layered chondrocyte sheets and cultured synovial cells

Ito, Satoshi; Sato, Masato; Yamato, Masayuki; Mitani, Genya; Kutsuna, Toshiharu; Nagai, Toshihiro; Ukai, Taku; Kobayashi, M; Kokubo, Mami; Okano, Teruo; Mochida, Joji

doi:10.1016/j.biomaterials.2012.03.073

Cited by 66 publications

(80 citation statements)

References 38 publications

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“…Hyaline cartilage regeneration induced by chondrocyte sheet transplantation has been confirmed in animal models of cartilage defects [1], [2], [3], [4]. Based on these results, we have conducted a clinical study using autologous knee chondrocyte sheets in patients with cartilage defects in the knee joint, including osteoarthritis patients.…”

Section: Introductionmentioning

confidence: 90%

Multilineage-differentiating stress-enduring (Muse)-like cells exist in synovial tissue

Toyoda

Sato

Takahashi

et al. 2019

Regenerative Therapy

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IntroductionCartilage regeneration is a promising therapy for restoring joint function in patients with cartilage defects. The limited availability of autologous chondrocytes or chondrogenic progenitor cells is an obstacle to its clinical application. We investigated the existence and chondrogenic potential of synovial membrane-derived multilineage-differentiating stress-enduring (Muse)-like cells as an alternative cell source for cartilage regeneration.MethodsCells positive for stage-specific embryonic antigen-3 (SSEA-3), a marker of Muse cells, were isolated from the synovial membranes of 6 of 8 patients (median age, 53.5 years; range 36–72 years) by fluorescence-activated cell sorting. SSEA-3-positive cells were cultured in methylcellulose to examine their ability to form Muse clusters that are similar to the embryoid bodies formed by human embryonic stem cells. Muse clusters were expanded and chondrogenic potential of M-cluster-derived MSCs examined using a pellet culture system. Chondrogenic differentiation was evaluated by proteoglycan, safranin O, toluidine blue and type II collagen staining. To evaluate the practicality of the procedure for isolating Muse-like cells, we compared chondrogenic potential of M-cluster derived MSCs with expanded cells derived from the clusters formed by unsorted synovial cells.ResultsSynovial membranes contained SSEA-3-positive cells that after isolation exhibited Muse-like characteristics such as forming clusters that expressed NANOG, OCT3/4, and SOX2. In the pellet culture system, cell pellets created from the M-cluster-derived MSCs exhibited an increase in wet weight, which implied an increase in extracellular matrix production, displayed metachromasia with toluidine blue and safranin O staining and were aggrecan-positive and type II collagen-positive by immunostaining. Unsorted synovial cells also formed clusters in methylcellulose culture, and the expanded cell population derived from them exhibited chondrogenic potential. The histological and immunohistochemical appearance of chondrogenic pellet created from unsorted synovial cell-derived cells were comparable with that from M-cluster-derived MSCs.ConclusionsMuse-like cells can be isolated from the human synovial membrane, even from older patients, and therefore may provide a source of multipotent cells for regenerative medicine. In addition, the cluster-forming cell population within synovial cells also has excellent chondrogenic potential. These cells may provide a more practical option for cartilage regeneration.

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Section: Introductionmentioning

confidence: 90%

Multilineage-differentiating stress-enduring (Muse)-like cells exist in synovial tissue

Toyoda

Sato

Takahashi

et al. 2019

Regenerative Therapy

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“…Accordingly, scaffolds may be loaded with GFs such as bone morphogenetic protein (BMP)-2 and TGF-b1 (Sellers et al, 1997;Sellers et al, 2000;Holland et al, 2005;Holland et al, 2007;Reyes et al, 2012), seeded with chondrocytes or MSCs Qi et al, 2011;Ito et al, 2012), or employed with combinations of both GFs and cells (Im and Lee, 2010;Wang et al, 2010). To date, only few studies compare MSCs and chondrocytes in cartilage defect repair.…”

Section: Introductionmentioning

confidence: 99%

Comparative, osteochondral defect repair: Stem cells versus chondrocytes versus Bone Morphogenetic Protein-2, solely or in combination

Reyes

Pec²,

Sánchez³

et al. 2013

eCM

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Full-thickness articular cartilage damage does not resolve spontaneously. Studies with growth factors, implantation of autologous chondrocytes and mesenchymal stem cells have led to variable, to some extent inconsistent, results. This work compares osteochondral knee-defect repair in rabbits upon implantation of a previously described alginate/ (poly(lactic-co-glycolic) acid (PLGA) osteochondral scaffold in distinct conditions. Systems were either in vitro pre-cultured with a small number of allogeneic chondrocytes under fibroblast growth factor (FGF)-2 stimulation or the same amount of allogeneic, marrow derived, mesenchymal stem cells (without any pre-differentiation), or loaded with microsphere-encapsulated bone morphogenetic protein (BMP)-2 within the alginate layer, or holding combinations of one or the other cell type with BMP-2. The experimental limit was 12 weeks, because a foregoing study with this release system had shown a maintained tissue response for at least 24 weeks post-operation. After only 6 weeks, histological analyses revealed newly formed cartilage-like tissue, which resembled the adjacent, normal cartilage in cell as well as BMP-2 treated defects, but cell therapy gave higher histological scores. This advantage evened out until 12 weeks. Combinations of cells and BMP-2 did not result in any additive or synergistic effect. Equally efficient osteochondral defect repair was achieved with chondrocyte, stem cell, and BMP-2 treatment. Expression of collagen X and collagen I, signs of ongoing ossification, were histologically undetectable, and the presence of aggrecan protein indicated cartilage-like tissue. In conclusion, further work should demonstrate whether spatiotemporally controlled, on-site BMP-2 release alone could become a feasible therapeutic approach to repair large osteochondral defects.

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“…Transplantation of synovial MSCs into full-thickness osteochondral defects of adult rabbits resulted in cartilage formation in the defect but some transplanted MSCs differentiated into bone cells in the deep zone, suggesting that synovial MSCs may differentiate into different lineage cells according to local microenvironments 81 . Several more recent animal studies further confirmed the repair process of AC defects using synovium-derived MSCs with or without scaffolds 69, 71, 72, 74 .…”

Section: The Link Between Development and Regenerationmentioning

confidence: 81%

Cell-based articular cartilage repair: the link between development and regeneration

Caldwell

Wang

2015

Osteoarthritis and Cartilage

145

111

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Context Clinical efforts to repair damaged articular cartilage (AC) currently face major obstacles due to limited intrinsic repair capacity of the tissue and unsuccessful biological interventions. This highlights a need for better therapeutic strategies. Evidence Acquisition Relevant articles were identified through a search of the PubMed database from January 1956 to August 2014 using the following keywords: articular cartilage repair, stem cell, cartilage tissue-engineering, synovium, and NFAT. Evidence Synthesis In both animals and humans, AC defects that penetrate into the subchondral bone marrow are mainly filled with fibrocartilaginous tissue through the differentiation of bone marrow mesenchymal stem cells (MSCs), followed by degeneration of repaired cartilage and osteoarthritis. Cell therapy and tissue engineering techniques using culture-expanded chondrocytes, bone marrow MSCs, or pluripotent stem cells with chondroinductive growth factors may generate cartilaginous tissue in AC defects but do not form hyaline cartilage-based articular surface because repair cells often lose chondrogenic activity or result in chondrocyte hypertrophy. The new evidence that AC and synovium develop from the same pool of precursors with similar gene profiles and that synovium-derived chondrocytes have stable chondrogenic activity has promoted use of synovium as a new cell source for AC repair. The recent finding that NFAT1 and NFAT2 transcription factors inhibit chondrocyte hypertrophy and maintain metabolic balance in AC is a significant advance in the field of AC repair. Conclusions The use of synovial MSCs and discovery of upstream transcriptional regulators that help maintain the AC phenotype have opened new avenues to improve the outcome of AC regeneration.

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Repair of articular cartilage defect with layered chondrocyte sheets and cultured synovial cells

Cited by 66 publications

References 38 publications

Multilineage-differentiating stress-enduring (Muse)-like cells exist in synovial tissue

Multilineage-differentiating stress-enduring (Muse)-like cells exist in synovial tissue

Comparative, osteochondral defect repair: Stem cells versus chondrocytes versus Bone Morphogenetic Protein-2, solely or in combination

Cell-based articular cartilage repair: the link between development and regeneration

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