The Regenerative Potential of Notochordal Cells in a Nucleus Pulposus Explant

Arkesteijn, Itm Irene; Potier, Esther; Ito, Keita

doi:10.1055/s-0036-1583174

Cited by 12 publications

(18 citation statements)

References 37 publications

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“…Cell Clusters 3 and 7 furthermore expressed HIGD2A (HIG1 Hypoxia Inducible Domain Family Member 2A), which is a hypoxia marker, and its expression is induced by the hypoxia-inducible factor-1 ( HIF1 ). Cell Cluster 7 additionally had an upregulation of XBP1 (X-box binding protein), a transcription factor and signal transducer involved in HIF1-alpha mediated hypoxia responses in survival [ 74 ], thus further supporting that these cell populations play in potentially detecting the environmental condition, ECM regulators and secreting soluble factors to maintain tissue homeostasis as indicated by the matrisome enrichment ( Figure S6 ) [ 75 , 76 , 77 ].…”

Section: Discussionmentioning

confidence: 95%

The Cellular Composition of Bovine Coccygeal Intervertebral Discs: A Comprehensive Single-Cell RNAseq Analysis

Caliò

Gantenbein

Egli

et al. 2021

IJMS

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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.

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Section: Discussionmentioning

confidence: 95%

The Cellular Composition of Bovine Coccygeal Intervertebral Discs: A Comprehensive Single-Cell RNAseq Analysis

Caliò

Gantenbein

Egli

et al. 2021

IJMS

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“…A wide range of potential cell-based therapies has been proposed for IVD regenerative strategies, and there have been extensive reviews on the use of cellular therapies for regeneration of the IVD [ 328 , 329 , 330 , 331 ]. Cellular strategies have ranged from studies on terminally differentiated chondrocytes [ 332 , 333 , 334 ] to more tissue-specific cell sources such as native disc cells from mature NP tissues [ 335 , 336 , 337 ] or immature notochordal cells from porcine discs [ 338 , 339 ]. There have been extensive studies using a number of stem cell sources, including MSC from bone marrow or adipose tissues [ 340 ].…”

Section: Ivd Regeneration Strategies: Biological Targets and Biomamentioning

confidence: 99%

Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research

Baumgartner

Wuertz‐Kozak

Maitre

et al. 2021

IJMS

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Intervertebral disc (IVD) degeneration is a major risk factor of low back pain. It is defined by a progressive loss of the IVD structure and functionality, leading to severe impairments with restricted treatment options due to the highly demanding mechanical exposure of the IVD. Degenerative changes in the IVD usually increase with age but at an accelerated rate in some individuals. To understand the initiation and progression of this disease, it is crucial to identify key top-down and bottom-up regulations’ processes, across the cell, tissue, and organ levels, in health and disease. Owing to unremitting investigation of experimental research, the comprehension of detailed cell signaling pathways and their effect on matrix turnover significantly rose. Likewise, in silico research substantially contributed to a holistic understanding of spatiotemporal effects and complex, multifactorial interactions within the IVD. Together with important achievements in the research of biomaterials, manifold promising approaches for regenerative treatment options were presented over the last years. This review provides an integrative analysis of the current knowledge about (1) the multiscale function and regulation of the IVD in health and disease, (2) the possible regenerative strategies, and (3) the in silico models that shall eventually support the development of advanced therapies.

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“…In parallel, the use of notochordal cells is also being considered, no matter from allogenic, autologous or xenogenic origin [103,104,105]. Risbud et al has previously proposed that morphology and size variation correlates to different stages of maturation and/or function of NP cells derived from notochordal precursors [106].…”

Section: Cell-based Therapiesmentioning

confidence: 99%

Intervertebral Disc Nucleus Repair: Hype or Hope?

Tendulkar

Chen

Ehnert

et al. 2019

IJMS

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Chronic back pain is a common disability, which is often accredited to intervertebral disc degeneration. Gold standard interventions such as spinal fusion, which are mainly designed to mechanically seal the defect, frequently fail to restore the native biomechanics. Moreover, artificial implants have limited success as a repair strategy, as they do not alter the underlying disease and fail to promote tissue integration and subsequent native biomechanics. The reported high rates of spinal fusion and artificial disc implant failure have pushed intervertebral disc degeneration research in recent years towards repair strategies. Intervertebral disc repair utilizing principles of tissue engineering should theoretically be successful, overcoming the inadequacies of artificial implants. For instance, advances in the development of scaffolds aided with cells and growth factors have opened up new possibilities for repair strategies. However, none has reached the stage of clinical trials in humans. In this review, we describe the hitches encountered in the musculoskeletal field and summarize recent advances in designing tissue-engineered constructs for promoting nucleus pulposus repair. Additionally, the review focuses on the effect of biomaterial aided with cells and growth factors on achieving effective functional reparative potency, highlighting the ways to enhance the efficacy of these treatments.

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The Regenerative Potential of Notochordal Cells in a Nucleus Pulposus Explant

Cited by 12 publications

References 37 publications

The Cellular Composition of Bovine Coccygeal Intervertebral Discs: A Comprehensive Single-Cell RNAseq Analysis

The Cellular Composition of Bovine Coccygeal Intervertebral Discs: A Comprehensive Single-Cell RNAseq Analysis

Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research

Intervertebral Disc Nucleus Repair: Hype or Hope?

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