Nucleus pulposus cell-matrix interactions with laminins

Gilchrist, C. L.; Francisco, AT; Plopper, G. E.; Chen, J; Setton, Lori A.

doi:10.22203/ecm.v021a39

Cited by 43 publications

(72 citation statements)

References 60 publications

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“…For this to be possible, a comprehensive phenotypic characterization of notochordal cells, and especially of markers specific to the notochordal cells in the human IVD would be required. To date, several attempts have been made to identify notochordal markers, either by comparing the gene expression of immature notochordal rat NP with its costal cartilage [73], rat NP tissue with different degrees of maturity [74][75][76], comparing immature pig NP with AF cells [74,77], sorted large and granular with smaller, less granular pig NP cells [78], immature human NP with AF cells [74] or NP from human juvenile scoliotic and adult discs [79] (Tables 1, 2, 3, 4 list putative notochordal/ immature NP markers identified in different species and describe their relevance to the IVD field). Proposed rat notochordal markers identified in these studies were CD55 [73], brachyury, neuropilin (Nrp-1), CD221, BASP-1 [76], N-Cad [73,76], TGF-b, BMP-6 and CTGF [75].…”

Section: T (Brachyury) Ratmentioning

confidence: 99%

“…Integrins and CD239 are expressed by NP cells and are responsible for their adhesion to laminins [74,77] Integrin subunits a3, a6 and ß4)…”

Section: Porcinementioning

confidence: 99%

“…This, in turn, will allow a more thorough understanding, at the molecular level, of the fate and role of notochordal or notochord-derived cells in the IVD and provide further insight into ways to tackle disc degeneration. Lamins are heterodimeric proteins involved in cell adhesion, migration, proliferation, differentiation and survival [74,77] Pending questions and potential clinical implications…”

Section: Cd239mentioning

confidence: 99%

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An understanding of intervertebral disc development, maturation and cell phenotype provides clues to direct cell-based tissue regeneration therapies for disc degeneration

2014

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Cell-based regenerative medicine therapies have been proposed for repairing the degenerated intervertebral disc (a major cause of back pain). However, for this approach to be successful, it is essential to characterise the phenotype of its native cells to guarantee that implanted cells differentiate and maintain the correct phenotype to ensure appropriate cell and tissue function. While recent studies have increased our knowledge of the human nucleus pulposus (NP) cell phenotype, their ontogeny is still unclear. The expression of notochordal markers by a subpopulation of adult NP cells suggests that, contrary to previous reports, notochord-derived cells are retained in the adult NP, possibly coexisting with a second population of cells originating from the annulus fibrosus or endplate. It is not known, however, how these two cell populations interact and their specific role(s) in disc homeostasis and disease. In particular, notochordal cells are proposed to display both anabolic and protective roles; therefore, they may be the ideal cells to repair the degenerate disc. Thus, understanding the ontogeny of the adult NP cells is paramount, as it will inform the medical and scientific communities as to the ideal phenotype to implant into the degenerate disc and the specific pathways involved in stem cell differentiation towards such a phenotype.

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Section: T (Brachyury) Ratmentioning

confidence: 99%

“…Integrins and CD239 are expressed by NP cells and are responsible for their adhesion to laminins [74,77] Integrin subunits a3, a6 and ß4)…”

Section: Porcinementioning

confidence: 99%

Section: Cd239mentioning

confidence: 99%

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An understanding of intervertebral disc development, maturation and cell phenotype provides clues to direct cell-based tissue regeneration therapies for disc degeneration

2014

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“…5,6,9 This work relied on enzymatic digestion protocols and plating on laminin-rich substrates to retain physaliphorous cells from the parent tumor that retain the CD24+ and T+ molecular profile of the parent tumor in cell culture and in xenografts generated in NOD/SCID/IL2Rγ null mice. Studies of isolated cells in culture and xenografts derived from these cells were compared with the U-CH1 and U-CH2b cell lines.…”

mentioning

confidence: 99%

Molecular characterization of chordoma xenografts generated from a novel primary chordoma cell source and two chordoma cell lines

Karikari¹,

Gilchrist

Jing

et al. 2014

SPI

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Object Chordoma cells can generate solid-like tumors in xenograft models that express some molecular characteristics of the parent tumor, including positivity for brachyury and cytokeratins. However, there is a dearth of molecular markers that relate to chordoma tumor growth, as well as the cell lines needed to advance treatment. The objective in this study was to isolate a novel primary chordoma cell source and analyze the characteristics of tumor growth in a mouse xenograft model for comparison with the established U-CH1 and U-CH2b cell lines. Methods Primary cells from a sacral chordoma, called “DVC-4,” were cultured alongside U-CH1 and U-CH2b cells for more than 20 passages and characterized for expression of CD24 and brachyury. While brachyury is believed essential for driving tumor formation, CD24 is associated with healthy nucleus pulposus cells. Each cell type was subcutaneously implanted in NOD/SCID/IL2Rγnull mice. The percentage of solid tumors formed, time to maximum tumor size, and immunostaining scores for CD24 and brachyury (intensity scores of 0–3, heterogeneity scores of 0–1) were reported and evaluated to test differences across groups. Results The DVC-4 cells retained chordoma-like morphology in culture and exhibited CD24 and brachyury expression profiles in vitro that were similar to those for U-CH1 and U-CH2b. Both U-CH1 and DVC-4 cells grew tumors at rates that were faster than those for U-CH2b cells. Gross tumor developed at nearly every site (95%) injected with U-CH1 and at most sites (75%) injected with DVC-4. In contrast, U-CH2b cells produced grossly visible tumors in less than 50% of injected sites. Brachyury staining was similar among tumors derived from all 3 cell types and was intensely positive (scores of 2–3) in a majority of tissue sections. In contrast, differences in the pattern and intensity of staining for CD24 were noted among the 3 types of cell-derived tumors (p < 0.05, chi-square test), with evidence of intense and uniform staining in a majority of U-CH1 tumor sections (score of 3) and more than half of the DVC-4 tumor sections (scores of 2–3). In contrast, a majority of sections from U-CH2b cells stained modestly for CD24 (scores of 1–2) with a predominantly heterogeneous staining pattern. Conclusions This is the first report on xenografts generated from U-CH2b cells in which a low tumorigenicity was discovered despite evidence of chordoma-like characteristics in vitro. For tumors derived from a primary chordoma cell and U-CH1 cell line, similarly intense staining for CD24 was observed, which may correspond to their similar potential to grow tumors. In contrast, U-CH2b tumors stained less intensely for CD24. These results emphasize that many markers, including CD24, may be useful in distinguishing among chordoma cell types and their tumorigenicity in vivo.

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“…In NPCs, a higher expression of the laminin a5 chain, laminin receptor integrin subunits a3, a6, and b4 along with CD239 and CD151 were found compared to cells from the AF [85]. Gilchrist et al also examined the cell-matrix interactions and found a faster cell spreading and a higher resistance to detachment on laminin isoforms LM-511 and LM-332, in contrast to LM-111, fibronectin, and collagen II [86]. Substrates coated with laminin softer than 720 Pa were also found to promote in vitro PG production [87].…”

Section: Integrin-mediated Interactions Between Npcs and Ecmmentioning

confidence: 99%

Reconstruction of an In Vitro Niche for the Transition from Intervertebral Disc Development to Nucleus Pulposus Regeneration

Shoukry

Pei

2013

Stem Cells and Development

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The nucleus pulposus (NP) plays a prominent role in both the onset and progression of intervertebral disc degeneration. While autologous repair strategies have demonstrated some success, their in vitro culture system is outdated and insufficient for maintaining optimally functioning cells through the required extensive passaging. Consequently, the final population of cells may be unsuitable for the overwhelming task of repairing tissue in vivo and could result in subpar clinical outcomes. Recent work has identified synovium-derived stem cells (SDSCs) as a potentially important new candidate. This population of precursors can promote matrix regeneration and additionally restore the balance of catabolic and anabolic metabolism of surrounding cells. Another promising application is their ability to produce an extracellular matrix in vitro that can be modified via decellularization to produce a tissue-specific substrate for efficient cell expansion, while retaining chondrogenic potential. When combined with hypoxia, soluble factors, and other environmental regulators, the resultant complex microenvironment will more closely resemble the in vivo niche, which further improves the cell capacity, even after extensive passaging. In this review, the adaptive mechanisms NP cells utilize in vivo are considered for insight into what factors are important for constructing a tissue-specific in vitro niche. Evidence for the use of SDSCs for NP regeneration is also discussed. Many aspects of NP behavior are still unknown, which could lead to future work yielding key information on producing sufficient numbers of a high-quality NPspecific population that is able to regenerate deteriorated NP in vivo.

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Nucleus pulposus cell-matrix interactions with laminins

Cited by 43 publications

References 60 publications

An understanding of intervertebral disc development, maturation and cell phenotype provides clues to direct cell-based tissue regeneration therapies for disc degeneration

An understanding of intervertebral disc development, maturation and cell phenotype provides clues to direct cell-based tissue regeneration therapies for disc degeneration

Molecular characterization of chordoma xenografts generated from a novel primary chordoma cell source and two chordoma cell lines

Reconstruction of an In Vitro Niche for the Transition from Intervertebral Disc Development to Nucleus Pulposus Regeneration

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