Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial

Mumme, Marcus; Barbero, Andrea; Miot, Sylvie; Wixmerten, Anke; Feliciano, Sandra; Wolf, Françine; Asnaghi, M. Adelaide; Baumhoer, Daniel; Bieri, Oliver; Kretzschmar, Martin; Pagenstert, Geert; Haug, Martin; Schaefer, Dirk J.; Martín, Iván; Jakob, Marcel

doi:10.1016/s0140-6736(16)31658-0

Cited by 203 publications

(181 citation statements)

References 30 publications

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“…In this respect, the presented data, strengthen the interest toward chondrocytes from the nasal septum, which show superior and more reproducible chondrogenic capacity, compared with chondrocytes from articular cartilage (Kafienah et al, 2002; Rotter et al, 2002; Wolf et al, 2008; Mumme et al, 2016). The comparison with articular chondrocytes demonstrated that nasal chondrocytes were able to support the production of a cartilage matrix with adequate functional and biomechanical characteristics both in vitro and in vivo (do Amaral et al, 2012; Pleumeekers et al, 2014).…”

Section: Discussionsupporting

confidence: 67%

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Dedifferentiated Chondrocytes in Composite Microfibers As Tool for Cartilage Repair

Angelozzi

Penolazzi

Mazzitelli

et al. 2017

Front. Bioeng. Biotechnol.

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Tissue engineering (TE) approaches using biomaterials have gain important roles in the regeneration of cartilage. This paper describes the production by microfluidics of alginate-based microfibers containing both extracellular matrix (ECM)-derived biomaterials and chondrocytes. As ECM components gelatin or decellularized urinary bladder matrix (UBM) were investigated. The effectiveness of the composite microfibers has been tested to modulate the behavior and redifferentiation of dedifferentiated chondrocytes. The complete redifferentiation, at the single-cell level, of the chondrocytes, without cell aggregate formation, was observed after 14 days of cell culture. Specific chondrogenic markers and high cellular secretory activity was observed in embedded cells. Notably, no sign of collagen type 10 deposition was determined. The obtained data suggest that dedifferentiated chondrocytes regain a functional chondrocyte phenotype when embedded in appropriate 3D scaffold based on alginate plus gelatin or UBM. The proposed scaffolds are indeed valuable to form a cellular microenvironment mimicking the in vivo ECM, opening the way to their use in cartilage TE.

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Section: Discussionsupporting

confidence: 67%

“…Chondrocytes derived from the nasal septum are highly promising cell source for the repair of articular cartilage defects since a great capacity to generate hyaline-like cartilage tissues, with the plasticity to adapt to a joint environment has been demonstrated (Kafienah et al, 2002; Wolf et al, 2008; Mumme et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

Dedifferentiated Chondrocytes in Composite Microfibers As Tool for Cartilage Repair

Angelozzi

Penolazzi

Mazzitelli

et al. 2017

Front. Bioeng. Biotechnol.

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“…In particular, human nasal chondrocytes have been considered as a clinically relevant source for cartilage engineering due to the high cellularity content and regenerative potential in terms of proliferative and synthetic capacities in biochemically distinct environments from their own such as joint and disc [21–27]. …”

Section: Introductionmentioning

confidence: 99%

Rapid Chondrocyte Isolation for Tissue Engineering Applications: The Effect of Enzyme Concentration and Temporal Exposure on the Matrix Forming Capacity of Nasal Derived Chondrocytes

Vedicherla

Buckley

2017

BioMed Research International

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Laboratory based processing and expansion to yield adequate cell numbers had been the standard in Autologous Disc Chondrocyte Transplantation (ADCT), Allogeneic Juvenile Chondrocyte Implantation (NuQu®), and Matrix-Induced Autologous Chondrocyte Implantation (MACI). Optimizing cell isolation is a key challenge in terms of obtaining adequate cell numbers while maintaining a vibrant cell population capable of subsequent proliferation and matrix elaboration. However, typical cell yields from a cartilage digest are highly variable between donors and based on user competency. The overall objective of this study was to optimize chondrocyte isolation from cartilaginous nasal tissue through modulation of enzyme concentration exposure (750 and 3000 U/ml) and incubation time (1 and 12 h), combined with physical agitation cycles, and to assess subsequent cell viability and matrix forming capacity. Overall, increasing enzyme exposure time was found to be more detrimental than collagenase concentration for subsequent viability, proliferation, and matrix forming capacity (sGAG and collagen) of these cells resulting in nonuniform cartilaginous matrix deposition. Taken together, consolidating a 3000 U/ml collagenase digest of 1 h at a ratio of 10 ml/g of cartilage tissue with physical agitation cycles can improve efficiency of chondrocyte isolation, yielding robust, more uniform matrix formation.

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“…This has expanded the role of nasal chondrocytes from facial cartilaginous structures (Fulco et al, 2014) to distant anatomical regions as knee articular cartilage defects (Mumme et al, 2016), paving the way for the use of NCs in IVD regeneration. In the present work we add to this emerging concept by demonstrating in vitro functionality using nasal derived chondrocytes compared to articular chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

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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Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial

Cited by 203 publications

References 30 publications

Dedifferentiated Chondrocytes in Composite Microfibers As Tool for Cartilage Repair

Dedifferentiated Chondrocytes in Composite Microfibers As Tool for Cartilage Repair

Rapid Chondrocyte Isolation for Tissue Engineering Applications: The Effect of Enzyme Concentration and Temporal Exposure on the Matrix Forming Capacity of Nasal Derived Chondrocytes

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

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