Differences in Cartilage-Forming Capacity of Expanded Human Chondrocytes from Ear and Nose and Their Gene Expression Profiles

Hellingman, Catharine A.; Verwiel, Eugène; Slagt, Inez K. B.; Koevoet, Wendy; Poublon, R. M. L.; Nolst-Trenité, Gilbert; Jong, Robert J. Baatenburg de; Jahr, Holger; Osch, Gerjo J.V.M. van

doi:10.3727/096368910x539119

Cited by 51 publications

(69 citation statements)

References 48 publications

(79 reference statements)

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“…In line with several studies using human nasal chondrocytes, we observed that bovine nasal chondrocytes retain good matrix accumulation properties post expansion (Chia et al, 2005;Hellingman et al, 2011;Malda et al, 2004;Richmon et al, 2005;Rotter et al, 2002;Tay et al, 2004). Importantly, physioxia (5% oxygen) is a potent environmental modulator of proliferation and matrix accumulation as demonstrated previously (Buckley et al, 2010;Twu et al, 2014).…”

Section: Discussionsupporting

confidence: 87%

“…Cell yield from NC was found to be higher compared with AC in line with previous studies (Hellingman et al, 2011;Pleumeekers et al, 2014;Tay et al, 2004). Although higher cell yields have been previously observed in auricular cartilage compared with NC, the ability to produce tissue in an age independent manner makes them an ideal cell source (Rotter et al, 2001(Rotter et al, , 2002Tay et al, 2004).…”

Section: Discussionsupporting

confidence: 87%

“…Nasal chondrocytes (NCs) (Bujia, 1995;Kafienah et al, 2002;Richmon et al, 2005) have been used to engineer cartilaginous constructs both in vitro and in vivo (Asawa et al, 2009;Candrian et al, 2008;Chia et al, 2005;Fulco et al, 2014;Hellingman et al, 2011;Malda et al, 2004;Richmon et al, 2005;Rotter et al, 2001Rotter et al, , 2002Scotti et al, 2012;Tsaryk et al, 2017;Twu et al, 2014;Watson and Reuther, 2014) and have recently been explored for nucleus pulposus tissue regeneration (Tsaryk et al, 2015;Tsaryk et al, 2017). However, the response of nasal chondrocytes to oxygen concentration and growth factors in maintaining phenotype and optimal NP-like matrix formation remains largely unknown in 3D culture.…”

Section: Introductionmentioning

confidence: 99%

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In vitro extracellular matrix accumulation of nasal and articular chondrocytes for intervertebral disc repair

Vedicherla

Buckley

2017

Tissue and Cell

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Chondrocyte based regenerative therapies for intervertebral disc repair such as Autologous Disc Cell Transplantation (ADCT, CODON) and allogeneic juvenile chondrocyte implantation (NuQu®, ISTO Technologies) have demonstrated good outcomes in clinical trials. However concerns remain with the supply demand reconciliation and issues surrounding immunoreactivity which exist for allogeneic-type technologies. The use of stem cells is challenging due to high growth factor requirements, regulatory barriers and differentiation towards a stable phenotype. Therefore, there is a need to identify alternative non-disc cell sources for the development and clinical translation of next generation therapies for IVD regeneration. In this study, we compared Nasal Chondrocytes (NC) as a non-disc alternative chondrocyte source with Articular Chondrocytes (AC) in terms of cell yield, morphology, proliferation kinetics and ability to produce key extracellular matrix components under 5% and 20% oxygen conditions, with and without exogenous TGF-β supplementation.Results indicated that NC maintained proliferative capacity with high amounts of sGAG and lower collagen accumulation in the absence of TGF-β supplementation under 5% oxygen conditions. Importantly, osteogenesis and calcification was inhibited for NC when cultured in IVD-like microenvironmental conditions. The present study provides a rationale for the exploration of nasal chondrocytes as a promising, potent and clinically feasible autologous cell source for putative IVD repair strategies.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In vitro extracellular matrix accumulation of nasal and articular chondrocytes for intervertebral disc repair

Vedicherla

Buckley

2017

Tissue and Cell

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“…To study whether cells in the alginate constructs harvested after in vivo implantation were of human origin, a monoclonal mouse anti-human vimentin antibody was used (AMF-17b, Developmental Studies Hybridoma Bank), as described previously (Hellingman et al, 2011). In short, slides were incubated in 3 % aqueous hydrogen peroxidase solution, in order to inhibit endogenous peroxidase and allow for peroxidase-antiperoxidase staining.…”

Section: Pleumeekers Et Al Comparison Of Cell Sources For Cartilamentioning

confidence: 99%

“…To date, we and others have evaluated the use of chondrocytes and MSCs of several anatomical locations for their applicability in cartilage regenerative medicine (Afizah et al, 2007;Asawa et al, 2009;Chung et al, 2008;Hellingman et al, 2011;Henderson et al, 2007;Isogai et al, 2006;Johnson et al, 2004;Kafienah et al, …”

Section: Introductionmentioning

confidence: 99%

The in vitro and in vivo capacity of culture-expanded human cells from several sources encapsulated in alginate to form cartilage

Pleumeekers

Nimeskern²,

Koevoet³

et al. 2014

eCM

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Cartilage has limited self-regenerative capacity. Tissue engineering can offer promising solutions for reconstruction of missing or damaged cartilage. A major challenge herein is to define an appropriate cell source that is capable of generating a stable and functional matrix. This study evaluated the performance of culture-expanded human chondrocytes from ear (EC), nose (NC) and articular joint (AC), as well as bone-marrow-derived and adipose-tissuederived mesenchymal stem cells both in vitro and in vivo. All cells (≥ 3 donors per source) were culture-expanded, encapsulated in alginate and cultured for 5 weeks. Subsequently, constructs were implanted subcutaneously for 8 additional weeks. Before and after implantation, glycosaminoglycan (GAG) and collagen content were measured using biochemical assays. Mechanical properties were determined using stress-strain-indentation tests. Hypertrophic differentiation was evaluated with qRT-PCR and subsequent endochondral ossification with histology. ACs had higher chondrogenic potential in vitro than the other cell sources, as assessed by gene expression and GAG content (p < 0.001). However, after implantation, ACs did not further increase their matrix. In contrast, ECs and NCs continued producing matrix in vivo leading to higher GAG content (p < 0.001) and elastic modulus. For NC-constructs, matrix-deposition was associated with the elastic modulus (R 2 = 0.477, p = 0.039). Although all cells -except ACsexpressed markers for hypertrophic differentiation in vitro, there was no bone formed in vivo. Our work shows that cartilage formation and functionality depends on the cell source used. ACs possess the highest chondrogenic capacity in vitro, while ECs and NCs are most potent in vivo, making them attractive cell sources for cartilage repair.

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Inhibiting calcineurin activity under physiologic tonicity elevates anabolic but suppresses catabolic chondrocyte markers

Windt¹,

Haak²,

Kops³

et al. 2012

Arthritis & Rheumatism

Self Cite

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Objective. The physiologic interstitial tonicity of healthy articular cartilage (350-480 mOsm) is lowered to 280-350 mOsm in osteoarthritis (OA). This results in loss of tissue prestress, altered compressive behavior, and, thus, inferior tissue properties. This study was undertaken to determine whether physiologic tonicity in combination with the inhibition of calcineurin (Cn) activity by FK-506 has synergistic effects on human articular chondrocytes and explants in vitro.Methods. OA chondrocytes and explants and non-OA chondrocytes were cultured in cytokine-free medium of 280 mOsm or 380 mOsm with or without Cn inhibition by FK-506. Chondrogenic, hypertrophic, and catabolic marker expression was evaluated at the messenger RNA (mRNA), protein, and activity levels.Results. Compared to OA chondrocytes cultured at 280 mOsm, those cultured at 380 mOsm had increased expression of mRNA for chondrogenic markers (e.g., ϳ13 fold for COL2; P < 0.001), and decreased COL1 expression (ϳ0.5 fold, P < 0.01). Inhibiting Cn activity under physiologic tonicity further enhanced the expression of anabolic markers at the mRNA level (ϳ50 fold for COL2; P < 0.001, ϳ2 fold for AGC1; P < 0.001, and ϳ3.5 fold for SOX9; P < 0.001) and at the protein level (ϳ6 fold for type II collagen; P < 0.001). Cn inhibition suppressed relevant collagenases as well as hypertropic and mineralization markers at the mRNA and activity levels. Expression of aggrecanase 1 and aggrecanase 2 was not influenced by tonicity or FK-506 alone, but the combination suppressed both, by ϳ50% (P < 0.05) and ϳ40% (P < 0.001), respectively. Generally, similar anabolic and antihypertrophic effects were observed in ex vivo cartilage explant cultures and non-OA chondrocytes.Conclusion. Our findings indicate that Cn at physiologic tonicity exerts a superior effect compared to physiologic tonicity or FK-506 alone, increasing anabolic markers while suppressing hypertrophic and catabolic markers. Our data may aid in the development of improved cell-based chondral repair and OA treatment strategies.Articular cartilage has unique properties related to the structure and composition of its extracellular matrix (ECM), which is mainly composed of proteoglycans (PGs), such as aggrecan, entangled in a network of collagen fibers, such as type II collagen, and large amounts of water (1). Water and inorganic salts represent the bulk mass portion, while collagens, PGs, and other glycoproteins and proteins constitute only 20% of the wet weight of the tissue. Collagens represent 50-60% of the dry weight of cartilage, while PGs, the second largest solid-phase portion, account for 5-10%.In normal cartilage there is a balance between matrix synthesis and degradation. Depletion of aggrecan from articular cartilage by matrix metalloproteinase (MMP) and aggrecanase (ADAMTS) action is an essential early pathophysiologic event in osteoarthritis (OA) (2-4). This decrease in PG content can result in reduced viscoelastic properties and increased deformation of

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Differences in Cartilage-Forming Capacity of Expanded Human Chondrocytes from Ear and Nose and Their Gene Expression Profiles

Cited by 51 publications

References 48 publications

In vitro extracellular matrix accumulation of nasal and articular chondrocytes for intervertebral disc repair

In vitro extracellular matrix accumulation of nasal and articular chondrocytes for intervertebral disc repair

The in vitro and in vivo capacity of culture-expanded human cells from several sources encapsulated in alginate to form cartilage

Inhibiting calcineurin activity under physiologic tonicity elevates anabolic but suppresses catabolic chondrocyte markers

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