Unique biomaterial compositions direct bone marrow stem cells into specific chondrocytic phenotypes corresponding to the various zones of articular cartilage

Nguyen, Lonnissa H.; Kudva, Abhijit K.; Guckert, Nicole L.; Linse, Klaus D.; Roy, Krishnendu

doi:10.1016/j.biomaterials.2010.10.009

Cited by 142 publications

(135 citation statements)

References 42 publications

(52 reference statements)

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“…[103][104][105][106] For instance, Annabi et al developed a two-stage solvent-free dense gas technique to produce porous 3D structures of natural/synthetic polymeric composites. 107 In the first stage, a gas-foaming/saltleaching process was used to create large pores with an average pore size of 540 -21 mm in a PCL matrix.…”

Section: -102mentioning

confidence: 99%

Vascularized Bone Tissue Engineering: Approaches for Potential Improvement

Nguyen

Annabi

Nikkhah³

et al. 2012

Tissue Engineering Part B: Reviews

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Section: -102mentioning

confidence: 99%

Vascularized Bone Tissue Engineering: Approaches for Potential Improvement

Nguyen

Annabi

Nikkhah³

et al. 2012

Tissue Engineering Part B: Reviews

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274

236

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“…For this reason, recent research has focused on the role of biomaterials or the roles played by hypoxia and chondrogenic factors to induce the redifferentiation of dedifferentiated chondrocytes. 19,33,34 However, a few cellular therapy approaches to inhibit type I collagen have shown great efficiency. We previously showed that dedifferentiated chondrocytes cultured in type I collagen sponges under hypoxia (3% O 2 ) express more type II collagen and aggrecan than in normoxia (21% O 2 ) and that BMP-2 favors this process.…”

Section: Discussionmentioning

confidence: 99%

BMP-2, Hypoxia, and COL1A1/HtrA1 siRNAs Favor Neo-Cartilage Hyaline Matrix Formation in Chondrocytes

Ollitrault

Legendre

Drougard

et al. 2015

Tissue Engineering Part C: Methods

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Osteoarthritis (OA) is an irreversible pathology that causes a decrease in articular cartilage thickness, leading finally to the complete degradation of the affected joint. The low spontaneous repair capacity of cartilage prevents any restoration of the joint surface, making OA a major public health issue. Here, we developed an innovative combination of treatment conditions to improve the human chondrocyte phenotype before autologous chondrocyte implantation. First, we seeded human dedifferentiated chondrocytes into a collagen sponge as a scaffold, cultured them in hypoxia in the presence of a bone morphogenetic protein (BMP), BMP-2, and transfected them with small interfering RNAs targeting two markers overexpressed in OA dedifferentiated chondrocytes, that is, type I collagen and/or HtrA1 serine protease. This strategy significantly decreased mRNA and protein expression of type I collagen and HtrA1, and led to an improvement in the chondrocyte phenotype index of differentiation. The effectiveness of our in vitro culture process was also demonstrated in the nude mouse model in vivo after subcutaneous implantation. We, thus, provide here a new protocol able to favor human hyaline chondrocyte phenotype in primarily dedifferentiated cells, both in vitro and in vivo. Our study also offers an innovative strategy for chondrocyte redifferentiation and opens new opportunities for developing therapeutic targets.

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“…9 Therefore, therapeutic interventions must either aim to prevent the loss of this layer at early disease stages, or to regenerate this layer in later disease stages. Growing attention has been focused on such regeneration of stratified repair tissue, [10][11][12] however, cell source remains a major challenge for zonal cartilage engineering efforts. Bone marrow-derived mesenchymal stem cells (MSCs) are potential treatment populations for articular cartilage defects.…”

mentioning

confidence: 99%

“…Typically, MSCs are cultured in a micromass or hydrogel and delivered chondrogenic media supplemented with transforming-growth factor bs (TGF-bs) and dexamethasone to induce chondrogenesis. Methods for inducing zone-specific chondryctes are yet to be established, but growth factor delivery 13 and cues from the scaffold environment 11 show potential for guiding progenitor populations to zone-specific cells.…”

mentioning

confidence: 99%

Engineering Superficial Zone Chondrocytes from Mesenchymal Stem Cells

Coates

Fisher

2014

Tissue Engineering Part C: Methods

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Recent cartilage engineering efforts have focused on development of zonally organized tissue. However, there remains a need for protocols that differentiate progenitor populations into chondrocytes of zonal phenotype. Here, we evaluate the potential of coculture of bovine mesenchymal stem cells (MSCs) and zonal explants of bovine cartilage tissue to drive MSC differentiation to chondrocytes with the superficial zone phenotype. Two coculture systems were set up: one between alginate encapsulated MSCs and superficial zone cartilage explants, and one between MSCs and middle/deep zone cartilage explants. Chondrogenic and superficial zone markers were monitored over a 21-day differentiation period via gene and protein expression. A control conditioned media study was used to determine the impact of communication via soluble factors between cell populations during differentiation. At day 21, results show superficial zone explant coculture without transforming-growth factor b3 supplementation induces upregulation of chondrogenic gene expression markers SOX9 and type II collagen 3.4-fold and 11.4-fold, respectively, over standard chondrogenic control media. Further, coculture of MSCs and superficial zone explants can be used to upregulate mRNA expression of the superficial zone marker proteoglycan-4 in MSCs (1.75-fold over chondrogenic control at day 21), indicating the superficial zone chondrocyte phenotype. Gene expression data show middle/deep zone explant and MSC coculture did not induce the chondrogenesis observed in superficial zone explant coculture. Likewise, poor chondrogenesis was observed in all conditioned media groups. Results highlight the importance of superficial zone cartilage and cells in guiding stem cell fate and regulating differentiation of MSCs to chondrocytes of the superficial zone type.

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Unique biomaterial compositions direct bone marrow stem cells into specific chondrocytic phenotypes corresponding to the various zones of articular cartilage

Cited by 142 publications

References 42 publications

Vascularized Bone Tissue Engineering: Approaches for Potential Improvement

Vascularized Bone Tissue Engineering: Approaches for Potential Improvement

BMP-2, Hypoxia, and COL1A1/HtrA1 siRNAs Favor Neo-Cartilage Hyaline Matrix Formation in Chondrocytes

Engineering Superficial Zone Chondrocytes from Mesenchymal Stem Cells

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