Development of a standardized histopathology scoring system for human intervertebral disc degeneration: an Orthopaedic Research Society Spine Section Initiative

Maitre, Christine L. Le; Dahia, Chitra Lekha; Giers, Morgan B.; Illien-Jünger, Svenja; Cicione, Claudia; Samartzis, D; Vadalà, Gianluca; Fields, Aaron J.; Lotz, Jeffrey C.

doi:10.1002/jsp2.1167

Cited by 33 publications

(45 citation statements)

References 102 publications

(136 reference statements)

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“…It is also important to note that human disc histopathology studies have revealed that not all degenerated discs exhibit calcification of the CEPs. 137 Therefore, this work sought to capture models of each grade with and without calcification, despite the limitation of generic models of each grade with mean parameters rather than a range of plausible bounds to the mean.…”

Section: Discussionmentioning

confidence: 99%

“…From this work, we can only speculate that the effect of calcification becomes more pertinent at Grade V, which we have already deemed too degenerated for cell‐based regeneration. It is also important to note that human disc histopathology studies have revealed that not all degenerated discs exhibit calcification of the CEPs 137 . Therefore, this work sought to capture models of each grade with and without calcification, despite the limitation of generic models of each grade with mean parameters rather than a range of plausible bounds to the mean.…”

Section: Discussionmentioning

confidence: 99%

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Consolidating and re‐evaluating the human disc nutrient microenvironment

McDonnell

Buckley

2022

JOR Spine

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Background Despite exciting advances in regenerative medicine, cell‐based strategies for treating degenerative disc disease remain in their infancy. To maximize the potential for successful clinical translation, a more thorough understanding of the in vivo microenvironment is needed to better determine and predict how cell therapies will respond when administered in vivo. Aims This work aims to reflect on the in vivo nutrient microenvironment of the degenerating IVD through consolidating what has already been measured together with investigative in silico models. Materials and Methods This work uses in silico modeling, underpinned by more recent experimentally determined parameters of degeneration and nutrient transport from the literature, to re‐evaluate the current knowledge in terms of grade‐specific stages of degeneration. Results Through modeling only the metabolically active cell population, this work predicts slightly higher glucose concentrations compared to previous in silico models, while the predicted results show good agreement with previous intradiscal pH and oxygen measurements. Increasing calcification with degeneration limits nutrient transport into the IVD and initiates a build‐up of acidity; however, its effect is compensated somewhat by a reduction in diffusional distance due to decreasing disc height. Discussion This work advances in silico modeling through a strong foundation of experimentally determined grade‐specific input parameters. Taken together, pre‐existing measurements and predicted results suggest that metabolite concentrations may not be as critically low as commonly believed, with calcification not appearing to have a detrimental effect at stages of degeneration when cell therapies are an appropriate intervention. Conclusion Overall, our initiative is to provoke greater deliberation and consideration of the nutrient microenvironment when performing in vitro cell culture and cell therapy development. This work highlights urgency for robust experimental glucose measurements in healthy and degenerating IVDs, not only to validate in silico models but to significantly advance the field in fully elucidating the nutrient microenvironment and refining in vitro techniques to accelerate clinical translation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Consolidating and re‐evaluating the human disc nutrient microenvironment

McDonnell

Buckley

2022

JOR Spine

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“…The disruption of this homeostatic balance is multifactorial, and may start at the cellular level caused by, for example, nutrient deprivation due to ossification of the endplates, or could initiate via a structural defect that can cause subsequent cellular changes. 28 The regulation of cellular turnover is vital to tissue homeostasis.…”

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confidence: 99%

Cell sources proposed for nucleus pulposus regeneration

et al. 2021

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Lower back pain (LBP) occurs in 80% of adults in their lifetime; resulting in LBP being one of the biggest causes of disability worldwide. Chronic LBP has been linked to the degeneration of the intervertebral disc (IVD). The current treatments for chronic back pain only provide alleviation of symptoms through pain relief, tissue removal, or spinal fusion; none of which target regenerating the degenerate IVD. As nucleus pulposus (NP) degeneration is thought to represent a key initiation site of IVD degeneration, cell therapy that specifically targets the restoration of the NP has been reviewed here. A literature search to quantitatively assess all cell types used in NP regeneration was undertaken. With key cell sources: NP cells; annulus fibrosus cells; notochordal cells; chondrocytes; bone marrow mesenchymal stromal cells; adiposederived stromal cells; and induced pluripotent stem cells extensively analyzed for their regenerative potential of the NP. This review highlights: accessibility; expansion capability in vitro; cell survival in an IVD environment; regenerative potential; and safety for these key potential cell sources. In conclusion, while several potential cell sources have been proposed, iPSC may provide the most promising regenerative potential.

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“…This review focuses on the nucleus pulposus cells of the human IVD. For representative examples of the other species used in disc (patho)biology the reader is referred to the recent series of a multi-species histopathological grading schemes reported for mice ( Melgoza et al, 2021 ), rats ( Lai et al, 2021 ), rabbits ( Gullbrand et al, 2021 ), large animal ( Lee et al, 2021 ), and human ( Le Maitre et al, 2021 ) discs.…”

Section: The Intervertebral Discmentioning

confidence: 99%

Notochordal Cell-Based Treatment Strategies and Their Potential in Intervertebral Disc Regeneration

Bach

Poramba‐Liyanage

Riemers

et al. 2022

Front. Cell Dev. Biol.

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Chronic low back pain is the number one cause of years lived with disability. In about 40% of patients, chronic lower back pain is related to intervertebral disc (IVD) degeneration. The standard-of-care focuses on symptomatic relief, while surgery is the last resort. Emerging therapeutic strategies target the underlying cause of IVD degeneration and increasingly focus on the relatively overlooked notochordal cells (NCs). NCs are derived from the notochord and once the notochord regresses they remain in the core of the developing IVD, the nucleus pulposus. The large vacuolated NCs rapidly decline after birth and are replaced by the smaller nucleus pulposus cells with maturation, ageing, and degeneration. Here, we provide an update on the journey of NCs and discuss the cell markers and tools that can be used to study their fate and regenerative capacity. We review the therapeutic potential of NCs for the treatment of IVD-related lower back pain and outline important future directions in this area. Promising studies indicate that NCs and their secretome exerts regenerative effects, via increased proliferation, extracellular matrix production, and anti-inflammatory effects. Reports on NC-like cells derived from embryonic- or induced pluripotent-stem cells claim to have successfully generated NC-like cells but did not compare them with native NCs for phenotypic markers or in terms of their regenerative capacity. Altogether, this is an emerging and active field of research with exciting possibilities. NC-based studies demonstrate that cues from developmental biology can pave the path for future clinical therapies focused on regenerating the diseased IVD.

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Development of a standardized histopathology scoring system for human intervertebral disc degeneration: an Orthopaedic Research Society Spine Section Initiative

Cited by 33 publications

References 102 publications

Consolidating and re‐evaluating the human disc nutrient microenvironment

Consolidating and re‐evaluating the human disc nutrient microenvironment

Cell sources proposed for nucleus pulposus regeneration

Notochordal Cell-Based Treatment Strategies and Their Potential in Intervertebral Disc Regeneration

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