Characterization of bovine and canine animal model cartilage endplates and comparison to human cartilage endplate structure, matrix composition, and cell phenotype
Abstract:There is a need to further explore mechanisms of cartilage endplate (CEP) degeneration, due to its role in the onset and progression of intervertebral disc degeneration and low back pain. Therefore, the goal of this study was to evaluate structure, matrix composition, and cell phenotype between the human and bovine or canine, both clinically relevant animal models currently used to study the intervertebral disc, CEP. This information may be used in addition to other relevant studies, to help determine optimal … Show more
“…Bovine IVDs are a widely used animal model for spine research as they offer the possibility to examine young and healthy tissues. Furthermore, the bovine model, while not a prefect substitute for the human model, has shown remarkable similarities in tissue specific marker expressions to the human model [ 41 , 48 ]. To reach our goal, we performed 10× Genomics single-cell RNA sequencing together with bulk RNAseq.…”
Intervertebral disc (IVD) degeneration and its medical consequences is still one of the leading causes of morbidity worldwide. To support potential regenerative treatments for degenerated IVDs, we sought to deconvolute the cell composition of the nucleus pulposus (NP) and the annulus fibrosus (AF) of bovine intervertebral discs. Bovine calf tails have been extensively used in intervertebral disc research as a readily available source of NP and AF material from healthy and young IVDs. We used single-cell RNA sequencing (scRNAseq) coupled to bulk RNA sequencing (RNAseq) to unravel the cell populations in these two structures and analyze developmental changes across the rostrocaudal axis. By integrating the scRNAseq data with the bulk RNAseq data to stabilize the clustering results of our study, we identified 27 NP structure/tissue specific genes and 24 AF structure/tissue specific genes. From our scRNAseq results, we could deconvolute the heterogeneous cell populations in both the NP and the AF. In the NP, we detected a notochordal-like cell cluster and a progenitor stem cell cluster. In the AF, we detected a stem cell-like cluster, a cluster with a predominantly fibroblast-like phenotype and a potential endothelial progenitor cluster. Taken together, our results illustrate the cell phenotypic complexity of the AF and NP in the young bovine IVDs.
“…Bovine IVDs are a widely used animal model for spine research as they offer the possibility to examine young and healthy tissues. Furthermore, the bovine model, while not a prefect substitute for the human model, has shown remarkable similarities in tissue specific marker expressions to the human model [ 41 , 48 ]. To reach our goal, we performed 10× Genomics single-cell RNA sequencing together with bulk RNAseq.…”
Intervertebral disc (IVD) degeneration and its medical consequences is still one of the leading causes of morbidity worldwide. To support potential regenerative treatments for degenerated IVDs, we sought to deconvolute the cell composition of the nucleus pulposus (NP) and the annulus fibrosus (AF) of bovine intervertebral discs. Bovine calf tails have been extensively used in intervertebral disc research as a readily available source of NP and AF material from healthy and young IVDs. We used single-cell RNA sequencing (scRNAseq) coupled to bulk RNA sequencing (RNAseq) to unravel the cell populations in these two structures and analyze developmental changes across the rostrocaudal axis. By integrating the scRNAseq data with the bulk RNAseq data to stabilize the clustering results of our study, we identified 27 NP structure/tissue specific genes and 24 AF structure/tissue specific genes. From our scRNAseq results, we could deconvolute the heterogeneous cell populations in both the NP and the AF. In the NP, we detected a notochordal-like cell cluster and a progenitor stem cell cluster. In the AF, we detected a stem cell-like cluster, a cluster with a predominantly fibroblast-like phenotype and a potential endothelial progenitor cluster. Taken together, our results illustrate the cell phenotypic complexity of the AF and NP in the young bovine IVDs.
“…In the deeper zones, chondrocytes become relatively round, hypertrophic, and gather in clusters. In contrast, the calcified cartilage zone contains only a small number of calcified cells [ 34 ]. Fig.…”
Section: Structures Components and Functions Of Cartilagementioning
The development of interdisciplinary biomedical engineering brings significant breakthroughs to the field of cartilage regeneration. However, cartilage defects are considerably more complicated in clinical conditions, especially when injuries occur at specific sites (
e.g.
, osteochondral tissue, growth plate, and weight-bearing area) or under inflammatory microenvironments (
e.g.
, osteoarthritis and rheumatoid arthritis). Therapeutic implantations, including advanced scaffolds, developed growth factors, and various cells alone or in combination currently used to treat cartilage lesions, address cartilage regeneration under abnormal conditions. This review summarizes the strategies for cartilage regeneration at particular sites and pathological microenvironment regulation and discusses the challenges and opportunities for clinical transformation.
“…The CEPs are populated by chondrocytes (1.5 × 10 4 cells/mm 3 ) [27,28] and whilst knowledge concerning phenotype is limited, COL10 has been identified as a potential CEP cell marker in adult IVDs [61]. CEP cells have also been shown to express high levels of the NP markers Brachyury and KRT19, plus the AF cell marker MKX [62]. Given the tissue's similarities with both NP and AF tissues, the CEPs and role of CEPrelated matrix cues deserve greater inclusion in future IVD discussions and regenerative approaches; CEP matrix cues and other instructive factors are almost certainly linked to NP and AF cell behaviour and phenotype, plus overall IVD development, homeostasis, ageing, and degeneration.…”
Back pain is one of the leading causes of disability worldwide and is frequently caused by degeneration of the intervertebral discs. The discs’ development, homeostasis, and degeneration are driven by a complex series of biochemical and physical extracellular matrix cues produced by and transmitted to native cells. Thus, understanding the roles of different cues is essential for designing effective cellular and regenerative therapies. Omics technologies have helped identify many new matrix cues; however, comparatively few matrix molecules have thus far been incorporated into tissue engineered models. These include collagen type I and type II, laminins, glycosaminoglycans, and their biomimetic analogues. Modern biofabrication techniques, such as 3D bioprinting, are also enabling the spatial patterning of matrix molecules and growth factors to direct regional effects. These techniques should now be applied to biochemically, physically, and structurally relevant disc models incorporating disc and stem cells to investigate the drivers of healthy cell phenotype and differentiation. Such research will inform the development of efficacious regenerative therapies and improved clinical outcomes.
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