Stem cells sources for intervertebral disc regeneration

Vadalà, Gianluca; Russo, Fabrizio; Ambrosio, Luigi; Loppini, Mattia; Denaro, Vincenzo

doi:10.4252/wjsc.v8.i5.185

Cited by 91 publications

(93 citation statements)

References 151 publications

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“…During the past decades, various kinds of cell sources were adopted in constructing cell-based scaffolds to regenerate degenerative discs, such as autologous or xenogenous NP cells and mesenchymal stem cells (MSCs) [42, 43]. Apart from the cell source, superior biocompatibility is another necessary requirement for cell-based scaffolds to regenerate degenerative discs.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Compression Promotes the Matrix Synthesis of Nucleus Pulposus Cells Through Up-Regulating N-CDH Expression in a Perfusion Bioreactor Culture

Yao

et al. 2018

Cell Physiol Biochem

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Background/Aims: An adequate matrix production of nucleus pulposus (NP) cells is an important tissue engineering-based strategy to regenerate degenerative discs. Here, we mainly aimed to investigate the effects and mechanism of mechanical compression (i.e., static compression vs. dynamic compression) on the matrix synthesis of three-dimensional (3D) cultured NP cells in vitro. Methods: Rat NP cells seeded on small intestinal submucosa (SIS) cryogel scaffolds were cultured in the chambers of a self-developed, mechanically active bioreactor for 10 days. Meanwhile, the NP cells were subjected to compression (static compression or dynamic compression at a 10% scaffold deformation) for 6 hours once per day. Unloaded NP cells were used as controls. The cellular phenotype and matrix biosynthesis of NP cells were investigated by real-time PCR and Western blotting assays. Lentivirus-mediated N-cadherin (N-CDH) knockdown and an inhibitor, LY294002, were used to further investigate the role of N-CDH and the PI3K/Akt pathway in this process. Results: Dynamic compression better maintained the expression of cell-specific markers (keratin-19, FOXF1 and PAX1) and matrix macromolecules (aggrecan and collagen II), as well as N-CDH expression and the activity of the PI3K/Akt pathway, in the 3D-cultured NP cells compared with those expression levels and activity in the cells grown under static compression. Further analysis showed that the N-CDH knockdown significantly down-regulated the expression of NP cell-specific markers and matrix macromolecules and inhibited the activation of the PI3K/Akt pathway under dynamic compression. However, inhibition of the PI3K/Akt pathway had no effects on N-CDH expression but down-regulated the expression of NP cell-specific markers and matrix macromolecules under dynamic compression. Conclusion: Dynamic compression increases the matrix synthesis of 3D-cultured NP cells compared with that of the cells under static compression, and the N-CDH-PI3K/Akt pathway is involved in this regulatory process. This study provides a promising strategy to promote the matrix deposition of tissue-engineered NP tissue in vitro prior to clinical transplantation.

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Section: Discussionmentioning

confidence: 99%

Dynamic Compression Promotes the Matrix Synthesis of Nucleus Pulposus Cells Through Up-Regulating N-CDH Expression in a Perfusion Bioreactor Culture

Yao

et al. 2018

Cell Physiol Biochem

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“…MSCs reside within the proteoglycan and noncollagenous protein‐rich matrix of the IVD, surrounded by the fibrous and cartilaginous outer AF region . The presence of MSCs within the IVD may implicate these cells in IVD healing, regeneration, and repair . In clinical applications, MSCs injected directly into the IVD space resulted in improvements in IVD hydration and collagenous tissue formation .…”

Section: Lessons From Models Of Mammalian Regenerationmentioning

confidence: 99%

“…140 The presence of MSCs within the IVD may implicate these cells in IVD healing, regeneration, and repair. 145 In clinical applications, MSCs injected directly into the IVD space resulted in improvements in IVD hydration and collagenous tissue formation. 146 In parallel, decreased structural degeneration-related parameters and patient-reported lumbar pain scores were also observed.…”

Section: Lessons From Models Of Mammalian Regenerationmentioning

confidence: 99%

Annulus fibrosus cell phenotypes in homeostasis and injury: implications for regenerative strategies

Torre

Mroz

Bartelstein

et al. 2018

Annals of the New York Academy of Sciences

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Despite considerable efforts to develop cellular, molecular, and structural repair strategies and restore intervertebral disk function after injury, the basic biology underlying intervertebral disk healing remains poorly understood. Remarkably, little is known about the origins of cell populations residing within the annulus fibrosus, or their phenotypes, heterogeneity, and roles during healing. This review focuses on recent literature highlighting the intrinsic and extrinsic cell types of the annulus fibrosus in the context of the injury and healing environment. Spatial, morphological, functional, and transcriptional signatures of annulus fibrosus cells are reviewed, including inner and outer annulus fibrosus cells, which we propose to be referred to as annulocytes. The annulus also contains peripheral cells, interlamellar cells, and potential resident stem/progenitor cells, as well as macrophages, T lymphocytes, and mast cells following injury. Phases of annulus fibrosus healing include inflammation and recruitment of immune cells, cell proliferation, granulation tissue formation, and matrix remodeling. However, annulus fibrosus healing commonly involves limited remodeling, with granulation tissues remaining, and the development of chronic inflammatory states. Identifying annulus fibrosus cell phenotypes during health, injury, and degeneration will inform reparative regeneration strategies aimed at improving annulus fibrosus healing.

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“…The robust repair potential of SCs in many tissues has drawn increased attention for treating IDD [20,21]. However, the harsh environment in IDD poses a tremendous challenge for exogenous cell survival due to limited nutrition and inflammatory conditions [22].…”

Section: Discussionmentioning

confidence: 99%

Cell properties of nucleus pulposus progenitor cells declines with intervertebral disc degeneration

Li¹,

Bai²,

Xin³

et al. 2017

Oncotarget

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Endogenous repair of nucleus pulposus progenitor cells (NPPCs) has exhibited encouraging regenerative potential for treating intervertebral disc degeneration (IDD). However, few studies have explored the properties of NPPCs during the progression of IDD. Hence, additional studies are needed to characterize NPPCs from human degenerated intervertebral disc (IVDs) at different Pfirrmann grades. In this study, human NPPCs were isolated and identified from human IVDs with different Pfirrmann grades. Then, cell biological characteristics, including proliferation, colony formation, cell senescence, migration capacity and chondrogenic ability, were compared. NPPCs were successfully harvested from grade I to IV IVDs, but not from grade V IVD due to the marked loss of nucleus pulposus tissue at grade V, leading to poor cell cultures. All four grades of NPPCs were identified as mesenchymal stem cells (MSCs) based on the criteria of the International Society for Cellular Therapy (ISCT) and shared similar cell morphological characteristics. In addition decreasing trends in proliferation, colony-formation capacity, migration, and chondrogenic ability and increasing levels of cell senescence; were detected in cells from grade I to IV IVDs, with significant changes between NPPCs of grade II and III. In summary, compared with NPPCs from normal IVDs (grade I), cells from degenerated IVDs (grades II to IV) exhibited gradually decreased cell properties and increased cell senescence. Grade II NPPCs displayed the optimal regeneration potential, suggesting that these NPPCs are an ideal candidate for endogenous repair of IDD.

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Stem cells sources for intervertebral disc regeneration

Cited by 91 publications

References 151 publications

Dynamic Compression Promotes the Matrix Synthesis of Nucleus Pulposus Cells Through Up-Regulating N-CDH Expression in a Perfusion Bioreactor Culture

Dynamic Compression Promotes the Matrix Synthesis of Nucleus Pulposus Cells Through Up-Regulating N-CDH Expression in a Perfusion Bioreactor Culture

Annulus fibrosus cell phenotypes in homeostasis and injury: implications for regenerative strategies

Cell properties of nucleus pulposus progenitor cells declines with intervertebral disc degeneration

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