Engineered nasal cartilage for the repair of osteoarthritic knee cartilage defects

Rua, Lina Acevedo; Mumme, Marcus; Manferdini, Cristina; Darwiche, Salim; Khalil, Ahmad M.; Hilpert, Morgane; Buchner, David A.; Lisignoli, Gina; Occhetta, Paola; Rechenberg, Brigitte von; Haug, Martin; Schaefer, Dirk J.; Jakob, Marcel; Caplan, Arnold I.; Martín, Iván; Barbero, Andrea; Pelttari, Karoliina

doi:10.1126/scitranslmed.aaz4499

Cited by 23 publications

(10 citation statements)

References 93 publications

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“…Therefore, if chondrocytes from one location were to be transplanted into a new location in the body, then genes required for these chondrocytes to properly differentiate in that new environment will ultimately be expressed, and cartilage will grow and differentiate in this new location in the body. Indeed, previous work has shown that when nasal chondrocytes are transplanted into an osteoarthritic knee, they can efficiently adapt to this new environment, and successfully contribute to cartilage repair (Pelttari et al, 2020;Acevedo Rua et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Limb Mesoderm and Head Ectomesenchyme Both Express a Core Transcriptional Program During Chondrocyte Differentiation

Gómez-Picos

Ovens

Eames

2022

Front. Cell Dev. Biol.

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To explain how cartilage appeared in different parts of the vertebrate body at discrete times during evolution, we hypothesize that different embryonic populations co-opted expression of a core gene regulatory network (GRN) driving chondrocyte differentiation. To test this hypothesis, laser-capture microdissection coupled with RNA-seq was used to reveal chondrocyte transcriptomes in the developing chick humerus and ceratobranchial, which are mesoderm- and neural crest-derived, respectively. During endochondral ossification, two general types of chondrocytes differentiate. Immature chondrocytes (IMM) represent the early stages of cartilage differentiation, while mature chondrocytes (MAT) undergo additional stages of differentiation, including hypertrophy and stimulating matrix mineralization and degradation. Venn diagram analyses generally revealed a high degree of conservation between chondrocyte transcriptomes of the limb and head, including SOX9, COL2A1, and ACAN expression. Typical maturation genes, such as COL10A1, IBSP, and SPP1, were upregulated in MAT compared to IMM in both limb and head chondrocytes. Gene co-expression network (GCN) analyses of limb and head chondrocyte transcriptomes estimated the core GRN governing cartilage differentiation. Two discrete portions of the GCN contained genes that were differentially expressed in limb or head chondrocytes, but these genes were enriched for biological processes related to limb/forelimb morphogenesis or neural crest-dependent processes, respectively, perhaps simply reflecting the embryonic origin of the cells. A core GRN driving cartilage differentiation in limb and head was revealed that included typical chondrocyte differentiation and maturation markers, as well as putative novel “chondrocyte” genes. Conservation of a core transcriptional program during chondrocyte differentiation in both the limb and head suggest that the same core GRN was co-opted when cartilage appeared in different regions of the skeleton during vertebrate evolution.

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Section: Discussionmentioning

confidence: 99%

Limb Mesoderm and Head Ectomesenchyme Both Express a Core Transcriptional Program During Chondrocyte Differentiation

Gómez-Picos

Ovens

Eames

2022

Front. Cell Dev. Biol.

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“…Human beta defensins are a group of antimicrobial molecules with tissue regenerative properties, e.g., HBD-2 is involved in bone defect reconstruction and also induces wound healing by stimulating granulation tissue to form and accelerating skin appendage regeneration [ 25 , 26 ]. Furthermore, nasal chondrocytes have been used in regenerative medicine in order to repair knee cartilage defects and we thus suspect that tracheal hyaline cartilage also could possess some beneficial properties [ 83 , 84 ].…”

Section: Discussionmentioning

confidence: 99%

Glycosaminoglycan, Antimicrobial Defence Molecule and Cytokine Appearance in Tracheal Hyaline Cartilage of Healthy Humans

Deņisova

Pilmane

Fedirko

2022

JFMK

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Hyaline cartilage is an important tracheal structure, yet little is known about its molecular composition, complicating investigation of pathologies and replacement options. Our aim was to research tracheal hyaline cartilage structure, protective tissue factors and variations in healthy humans. The tissue material was obtained from 10 cadavers obtained from the Riga Stradins University Institute of Anatomy and Anthropology archive. Tissues were stained with Bismarck brown and PAS for glycosaminoglycans, and immunohistochemistry was performed for HBD-2, HBD-3, HBD-4, IL-10 and LL-37. The slides were inspected by light microscopy and Spearman’s rank correlation coefficient was calculated. The extracellular matrix was positive across hyaline cartilage for PAS, yet Bismarck brown marked positive proliferation and growth zones. Numerous positive cells for both factors were found in all zones. All of the antimicrobial defence molecules and cytokines were found in a moderate number of cells, except in the mature cell zone with few positive cells. Spearman’s rank correlation coefficient revealed strong and moderate correlations between studied factors. Hyaline cartilage is a tracheal defence structure with a moderate number of antimicrobial defence protein and cytokine immunoreactive cells as well as numerous glycosaminoglycan positive cells. The extracellular matrix glycosaminoglycans provide structural scaffolding and intercellular signalling. The correlations between the studied factors confirm the synergistic activity of them.

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“…NC exhibit features of self-renewal and adapt to heterotopic transplantation sites, including osteoarthritic knee cartilage defects [ 71 , 72 , 73 ]. Engineered NC cartilage grafts are already being used to repair cartilage defects in patients [ 74 , 75 ]. Neuroectoderm-derived NC can be distinguished from mesoderm-derived AC by lack of expression of specific HOX genes and reprogrammed to stably express HOX genes typical for AC, as shown in goat articular cartilage defects [ 71 ].…”

Section: Cell Sources For Ivd Tissue Engineeringmentioning

confidence: 99%

Spheroid-Based Tissue Engineering Strategies for Regeneration of the Intervertebral Disc

Kasamkattil

Gryadunova

Martin

et al. 2022

IJMS

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Degenerative disc disease, a painful pathology of the intervertebral disc (IVD), often causes disability and reduces quality of life. Although regenerative cell-based strategies have shown promise in clinical trials, none have been widely adopted clinically. Recent developments demonstrated that spheroid-based approaches might help overcome challenges associated with cell-based IVD therapies. Spheroids are three-dimensional multicellular aggregates with architecture that enables the cells to differentiate and synthesize endogenous ECM, promotes cell-ECM interactions, enhances adhesion, and protects cells from harsh conditions. Spheroids could be applied in the IVD both in scaffold-free and scaffold-based configurations, possibly providing advantages over cell suspensions. This review highlights areas of future research in spheroid-based regeneration of nucleus pulposus (NP) and annulus fibrosus (AF). We also discuss cell sources and methods for spheroid fabrication and characterization, mechanisms related to spheroid fusion, as well as enhancement of spheroid performance in the context of the IVD microenvironment.

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Engineered nasal cartilage for the repair of osteoarthritic knee cartilage defects

Abstract: Nasal chondrocyte–based grafts modulate osteoarthritis-like conditions in animal models and improve life quality in patients with knee osteoarthritis.

Cited by 23 publications

References 93 publications

Limb Mesoderm and Head Ectomesenchyme Both Express a Core Transcriptional Program During Chondrocyte Differentiation

Limb Mesoderm and Head Ectomesenchyme Both Express a Core Transcriptional Program During Chondrocyte Differentiation

Glycosaminoglycan, Antimicrobial Defence Molecule and Cytokine Appearance in Tracheal Hyaline Cartilage of Healthy Humans

Spheroid-Based Tissue Engineering Strategies for Regeneration of the Intervertebral Disc

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