Potential benefits and limitations of utilizing chondroprogenitors in cell-based cartilage therapy

Jayasuriya, Chathuraka T.; Chen, Qian

doi:10.3109/03008207.2015.1040547

Cited by 46 publications

(57 citation statements)

References 65 publications

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“…C-PCs consist of less than 1% of cells found in healthy articular cartilage [33, 34]. Similarly, BM-MSCs also consist of <1% of all stromal cells in the bone marrow [35].…”

Section: Discussionmentioning

confidence: 99%

Human Cartilage-Derived Progenitors Resist Terminal Differentiation and Require CXCR4 Activation to Successfully Bridge Meniscus Tissue Tears

et al. 2018

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Meniscus injuries are among the most common orthopaedic injuries. Tears in the inner one-third of the meniscus heal poorly and present a significant clinical challenge. In this study, we hypothesized that progenitor cells from healthy human articular cartilage (C-PCs) may be more suitable than bone-marrow mesenchymal stem cells (BM-MSCs) to mediate bridging and reintegration of fibrocartilage tissue tears in meniscus. C-PCs were isolated from healthy human articular cartilage based on their expression of mesenchymal stem/progenitor marker ALCAM (CD166). Our findings revealed that healthy human C-PCs are CD166+, CD90+, CD54+, CD106- cells with multi-lineage differentiation potential and elevated basal expression of chondrogenesis marker SOX-9. We show that, similar to BM-MSCs, C-PCs are responsive to the chemokine stromal cell derived factor-1 (SDF-1) and they can successfully migrate to the area of meniscal tissue damage promoting collagen bridging across inner meniscal tears. In contrast to BM-MSCs, C-PCs maintaining reduced expression of cellular hypertrophy marker collagen X in monolayer culture and in an ex-plant organ culture model of meniscus repair. Treatment of C-PCs with SDF-1/CXCR4 pathway inhibitor AMD3100 disrupted cell localization to area of injury and prevented meniscus tissue bridging thereby indicating that the SDF-1/CXCR4 axis is an important mediator of this repair process. This study suggests that C-PCs from healthy human cartilage may potentially be a useful tool for fibrocartilage tissue repair/regeneration because they resist cellular hypertrophy and mobilize in response to chemokine signaling.

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“…C-PCs consist of less than 1% of cells found in healthy articular cartilage [33, 34]. Similarly, BM-MSCs also consist of <1% of all stromal cells in the bone marrow [35].…”

Section: Discussionmentioning

confidence: 99%

Human Cartilage-Derived Progenitors Resist Terminal Differentiation and Require CXCR4 Activation to Successfully Bridge Meniscus Tissue Tears

et al. 2018

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“…Firstly, these cells are isolated from local tissue and have been shown to possess sufficient proliferative capacity for expansion without losing their propensity for chondrogenic differentiation. Compared to MSCs from bone marrow and adipose-derived progenitors, articular cartilage-derived stem cells are believed to be further along in their commitment to the chondrogenic lineage, primed to differentiate to form hyaline cartilage, making them a logical choice for tissue engineering (Jayasuriya and Chen, 2015). Moreover, articular CPCs, unlike marrow stromal mesenchymal cells do not terminally differentiate toward an epiphyseal lineage producing hypertrophic chondrocytes.…”

Section: Tissue Reservoirs Of Mscsmentioning

confidence: 99%

Adipose, Bone Marrow and Synovial Joint-Derived Mesenchymal Stem Cells for Cartilage Repair

et al. 2016

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Current cell-based repair strategies have proven unsuccessful for treating cartilage defects and osteoarthritic lesions, consequently advances in innovative therapeutics are required and mesenchymal stem cell-based (MSC) therapies are an expanding area of investigation. MSCs are capable of differentiating into multiple cell lineages and exerting paracrine effects. Due to their easy isolation, expansion, and low immunogenicity, MSCs are an attractive option for regenerative medicine for joint repair. Recent studies have identified several MSC tissue reservoirs including in adipose tissue, bone marrow, cartilage, periosteum, and muscle. MSCs isolated from these discrete tissue niches exhibit distinct biological activities, and have enhanced regenerative potentials for different tissue types. Each MSC type has advantages and disadvantages for cartilage repair and their use in a clinical setting is a balance between expediency and effectiveness. In this review we explore the challenges associated with cartilage repair and regeneration using MSC-based cell therapies and provide an overview of phenotype, biological activities, and functional properties for each MSC population. This paper also specifically explores the therapeutic potential of each type of MSC, particularly focusing on which cells are capable of producing stratified hyaline-like articular cartilage regeneration. Finally we highlight areas for future investigation. Given that patients present with a variety of problems it is unlikely that cartilage regeneration will be a simple “one size fits all,” but more likely an array of solutions that need to be applied systematically to achieve regeneration of a biomechanically competent repair tissue.

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“…When expression of markers indicating chondrogenic potential was assessed we found that both cell populations exhibited high levels of CD9, CD29, CD151 and CD49e with no significant difference between the two (Fig 8). CD49e which forms a heterodimeric fibronectin receptor along with integrin β1(CD29), has been defined as a definitive marker for CPs, and forms the basis for their isolation employing fibronectin differential adhesion assay(17,28). A very important observation was that all chondrocyte groups including freshly isolated cells expressed high levels of CD49e and CD29, matching those expressed in CPs.…”

Section: Discussionmentioning

confidence: 99%

“…The second category for comparison included markers considered to be expressed specifically by chondrocytes: CD54(25) and CD44(27). The final category for comparison included CD markers which are reported to be expressed by cells exhibiting enhanced chondrogenic potential: CD9(28), CD29(29), CD151(30), CD49e(22,28), CD166(31) and CD146(32). To differentiate chondrocytes and CPs on the basis of their chondrogenic potential and tendency for hypertrophy, mRNA expression for markers of chondrogenesis (Collagen type II, Aggrecan and SOX9) and of hypertrophy (Collagen type I, Collagen type X, RUNX2 and MMP-13) was analyzed(33).…”

Section: Introductionmentioning

confidence: 99%

In vitro characterization of human articular chondrocytes and chondroprogenitors derived from normal and osteoarthritic knee joints

Vinod

Kachroo

Sathishkumar

et al. 2018

Preprint

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ObjectiveCell based therapy optimization is constantly underway since regeneration of genuine hyaline cartilage is under par. Although single source derivation of chondrocytes and chondroprogenitors is advantageous, lack of a characteristic differentiating marker obscures clear identification of either cell type which is essential to create a biological profile and is also required to assess cell type superiority for cartilage repair. This study was the first attempt where characterization was performed on the two cell populations derived from the same human articular cartilage samples.DesignCells obtained from normal/osteoarthritic knee joints were expanded in culture (up to passage 10). Characterization studies was performed using flow cytometry, gene expression was studied using RT-PCR, growth kinetics and tri-lineage differentiation was also studied to construct a better biological profile of chondroprogenitors as well as chondrocytes.Results and conclusionsOur results suggest that sorting based on CD34(-), CD166(+) and CD146(+), instead of isolation using fibronectin adhesion assay (based on CD49e+/CD29+), would yield a population of cells primarily composed of chondroprogenitors which when derived from normal as opposed to osteoarthritic cartilage, could provide translatable results in terms of enhanced chondrogenesis and reduced hypertrophy; both indispensable for the field of cartilage regeneration.

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Potential benefits and limitations of utilizing chondroprogenitors in cell-based cartilage therapy

Cited by 46 publications

References 65 publications

Human Cartilage-Derived Progenitors Resist Terminal Differentiation and Require CXCR4 Activation to Successfully Bridge Meniscus Tissue Tears

Human Cartilage-Derived Progenitors Resist Terminal Differentiation and Require CXCR4 Activation to Successfully Bridge Meniscus Tissue Tears

Adipose, Bone Marrow and Synovial Joint-Derived Mesenchymal Stem Cells for Cartilage Repair

In vitro characterization of human articular chondrocytes and chondroprogenitors derived from normal and osteoarthritic knee joints

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