Nose to Spine: spheroids generated by human nasal chondrocytes for scaffold-free nucleus pulposus augmentation

Gryadunova, A. A.; Kasamkattil, Jesil; Dasen, Boris; Pelttari, Karoliina; Mironov, Vladimir; Martín, Iván; Schären, Stefan; Barbero, Andrea; Krupková, Olga; Mehrkens, Arne

doi:10.1016/j.actbio.2021.07.064

Cited by 13 publications

(16 citation statements)

References 69 publications

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“…The constructs exhibited significant ECM accumulation in vitro and excellent integration with surrounding cartilage tissues in vivo [ 65 ]. Tuneability, injectability, and biomechanical superiority of human nasal chondrocytes (hNCs) have been confirmed by Gryadunova et al Injecting hNC spheroids to the explants of bovine intervertebral disc has illustrated its great potential for regeneration of nucleus pulposus (NP) in a minimally invasive procedure [ 66 ]. Three dimensional (3D) scaffold-free hyaline cartilage constructs with clinically relevant size were derived from human embryonic stem cells (hESCs).…”

Section: Recruiting Cells To Achieve Csimentioning

confidence: 99%

New Insights into Cartilage Tissue Engineering: Improvement of Tissue-Scaffold Integration to Enhance Cartilage Regeneration

Jelodari

Sadrabadi

Zarei

et al. 2022

BioMed Research International

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Distinctive characteristics of articular cartilage such as avascularity and low chondrocyte conversion rate present numerous challenges for orthopedists. Tissue engineering is a novel approach that ameliorates the regeneration process by exploiting the potential of cells, biodegradable materials, and growth factors. However, problems exist with the use of tissue-engineered construct, the most important of which is scaffold-cartilage integration. Recently, many attempts have been made to address this challenge via manipulation of cellular, material, and biomolecular composition of engineered tissue. Hence, in this review, we highlight strategies that facilitate cartilage-scaffold integration. Recent advances in where efficient integration between a scaffold and native cartilage could be achieved are emphasized, in addition to the positive aspects and remaining problems that will drive future research.

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Section: Recruiting Cells To Achieve Csimentioning

confidence: 99%

New Insights into Cartilage Tissue Engineering: Improvement of Tissue-Scaffold Integration to Enhance Cartilage Regeneration

Jelodari

Sadrabadi

Zarei

et al. 2022

BioMed Research International

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“…The structure remains uniformly spherical and appears to be uniformly compact and it is characterized by cells that are in close contact with each other . Spheroids are homogeneous, well-rounded, and solid cell aggregates. , Over time, shrinkage of the spheroids and the formation of a necrotic core are often observed as the ability of the cells to proliferate is compromised . This behavior is also described in the literature for spheroids formed by other primary cells and cell lines as well as by mesenchymal stem cells (MSCs). , The dynamic process of chondro-aggregates formation in the presence of CTL appears to be substantially different from the one described in the literature, where cell aggregation occurs by preventing cell adhesion on a substrate.…”

Section: Discussionmentioning

confidence: 76%

Bioactive Lactose-Modified Chitosan Acts as a Temporary Extracellular Matrix for the Formation of Chondro-Aggregates

Pizzolitto

Scognamiglio

Baldini

et al. 2022

ACS Appl. Polym. Mater.

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Spheroids based on chondrocytes are gaining interest in the treatment of injured cartilage tissue due to their regenerative potential. In this study, chondrocyte-based aggregates were formed by culturing cells on a polymeric coating of a lactose-modified chitosan (CTL) and their evolution was followed for 14 days of culture. Morphological analyses through scanning electron microscopy indicated that these cell aggregates formed by a process of cell aggregation rather than proliferation, resulting in structures with an irregular morphology that were up to 1 mm in size. Chondrocytes interact very closely with CTL. In the early days of cellular aggregation, CTL is distributed among the cells, while in later stages, it is localized in the inner part of the aggregates, forming an amorphous matrix. The initial outer position of the polymer is replaced over time by an increased matrix deposition whose main component is type II collagen. Transmission electron microscopy pointed out that the chondrocytes internalized the polymer during the first days of culture. The presence of CTL does not affect the ability of cells to migrate from chondro-aggregates when transferred to uncoated wells, mimicking the ability of cells to colonize a cartilage defect. Overall, these results suggest that CTL plays a role as a temporary matrix for chondrocytes aggregation during chondro-aggregates formation. This opens up innovative therapeutic approaches for cartilage regeneration without the need to use a scaffold to deliver cells to the damaged site.

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“…For early stage IVD repair, therapeutic cells have to reside, survive, resist inflammation and produce ECM within the degenerative NP tissue. In previous studies, NC showed superior viability in simulated DDD microenvironment over commonly used MSCs and AC, thus represent a promising cell source for IVD repair (Vedicherla and Buckley, 2017;Gay et al, 2019;Borrelli and Buckley, 2020;Gryadunova et al, 2021). In degenerative IVD condition, NC were reported to produce a ratio of low collagen to high GAG content whereas AC produce less favorable high collagen ratios (Vedicherla and Buckley, 2017).…”

Section: Discussionmentioning

confidence: 96%

Human 3D nucleus pulposus microtissue model to evaluate the potential of pre-conditioned nasal chondrocytes for the repair of degenerated intervertebral disc

Kasamkattil

Gryadunova²,

Schmid³

et al. 2023

Front. Bioeng. Biotechnol.

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Introduction: An in vitro model that appropriately recapitulates the degenerative disc disease (DDD) microenvironment is needed to explore clinically relevant cell-based therapeutic strategies for early-stage degenerative disc disease. We developed an advanced 3D nucleus pulposus (NP) microtissues (µT) model generated with cells isolated from human degenerating NP tissue (Pfirrmann grade: 2–3), which were exposed to hypoxia, low glucose, acidity and low-grade inflammation. This model was then used to test the performance of nasal chondrocytes (NC) suspension or spheroids (NCS) after pre-conditioning with drugs known to exert anti-inflammatory or anabolic activities.Methods: NPµTs were formed by i) spheroids generated with NP cells (NPS) alone or in combination with ii) NCS or iii) NC suspension and cultured in healthy or degenerative disc disease condition. Anti-inflammatory and anabolic drugs (amiloride, celecoxib, metformin, IL-1Ra, GDF-5) were used for pre-conditioning of NC/NCS. The effects of pre-conditioning were tested in 2D, 3D, and degenerative NPµT model. Histological, biochemical, and gene expression analysis were performed to assess matrix content (glycosaminoglycans, type I and II collagen), production and release of inflammatory/catabolic factors (IL-6, IL-8, MMP-3, MMP-13) and cell viability (cleaved caspase 3).Results: The degenerative NPµT contained less glycosaminoglycans, collagens, and released higher levels of IL-8 compared to the healthy NPµT. In the degenerative NPµT, NCS performed superior compared to NC cell suspension but still showed lower viability. Among the different compounds tested, only IL-1Ra pre-conditioning inhibited the expression of inflammatory/catabolic mediators and promoted glycosaminoglycan accumulation in NC/NCS in DDD microenvironment. In degenerative NPµT model, preconditioning of NCS with IL-1Ra also provided superior anti-inflammatory/catabolic activity compared to non-preconditioned NCS.Conclusion: The degenerative NPµT model is suitable to study the responses of therapeutic cells to microenvironment mimicking early-stage degenerative disc disease. In particular, we showed that NC in spheroidal organization as compared to NC cell suspension exhibited superior regenerative performance and that IL-1Ra pre-conditioning of NCS could further improve their ability to counteract inflammation/catabolism and support new matrix production within harsh degenerative disc disease microenvironment. Studies in an orthotopic in vivo model are necessary to assess the clinical relevance of our findings in the context of IVD repair.

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Nose to Spine: spheroids generated by human nasal chondrocytes for scaffold-free nucleus pulposus augmentation

Cited by 13 publications

References 69 publications

New Insights into Cartilage Tissue Engineering: Improvement of Tissue-Scaffold Integration to Enhance Cartilage Regeneration

New Insights into Cartilage Tissue Engineering: Improvement of Tissue-Scaffold Integration to Enhance Cartilage Regeneration

Bioactive Lactose-Modified Chitosan Acts as a Temporary Extracellular Matrix for the Formation of Chondro-Aggregates

Human 3D nucleus pulposus microtissue model to evaluate the potential of pre-conditioned nasal chondrocytes for the repair of degenerated intervertebral disc

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