Modeling Nucleus Pulposus Regeneration In Vitro

McCanless, Jonathan D.; Cole, Jon C.; Slack, Steven M.; Bumgardner, Joel D.; Zamora, Paul O.; Haggard, Warren O.

doi:10.1097/brs.0b013e31820cd1b1

Cited by 10 publications

(6 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may explain the improved accumulation of matrix observed in alginate compared with chitosan since a change in NP cell morphology from round to a more spread-like shape in chitosan hydrogels was observed possibly suggesting a change in cell phenotype. This is in agreement with several studies which have previously shown that NP cells remain phenotypically stable in alginate throughout the culture period (47,48 sGAG/Collagen ratio. * denotes significance compared to chitosan (p<0.05); # denoted significance compared to 8x10 6 cell/ml seeding density group (p<0.05).…”

Section: Discussionsupporting

confidence: 82%

“…Previous studies have shown that NP and BM cells remain viable, proliferate and synthesise matrix (collagen type II and GAG) in alginate (30,31,(47)(48)(49)(50) and chitosan (17, 34, 51). In our hands and culture conditions, alginate more readily maintained and supported NP and BM cell viability with increased cell proliferation compared to chitosan at both seeding densities when cultured in isolation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Differential Response of Encapsulated Nucleus Pulposus and Bone Marrow Stem Cells in Isolation and Coculture in Alginate and Chitosan Hydrogels

Naqvi

Buckley

2015

Tissue Engineering Part A

View full text Add to dashboard Cite

Cell-based therapies may hold significant promise for the treatment of early stage degeneration of the intervertebral disc (IVD). Given their propensity to proliferate and ability to form multiple tissue types, mesenchymal stem cells (MSCs) have been proposed as a potential cell source to promote repair of the nucleus pulposus (NP). However, for any successful cell-based therapy a carrier biomaterial may be essential for targeted delivery providing key biophysical and biochemical cues to facilitate differentiation of MSCs. Two widely used biomaterials for NP regeneration are chitosan and alginate. The primary objective of this study was to assess the influence of alginate and chitosan hydrogels on bone marrow (BM) MSCs and NP cells in isolation or in co-culture. A secondary objective of this study was to investigate co-culture seeding density effects of BM and NP cells and simultaneously explore which cell type is responsible for matrix formation in a co-cultured environment. Porcine NP and BM cells were encapsulated in alginate and chitosan hydrogels separately at two seeding densities (4x10 6 and 8x10 6 cells/ml) or in co-culture (1:1, 8 x10 6 cells/ml). Constructs (diameter:5mm, height:3mm) were maintained under IVD-like conditions (low-glucose, low (5%) oxygen) with or without TGF-β3 supplementation for 21 days. Results demonstrated differential viability depending on hydrogel type. NP cells remained viable in both biomaterial types whereas BM viability was diminished in chitosan.Furthermore, hydrogel type was found to regulate sGAG and collagen accumulation.Specifically, alginate better supports sGAG accumulation and collagen type II deposition for both NP and BM cell types compared to chitosan. Having identified that alginate more readily supports cell viability and matrix accumulation we further explored additional effects of seeding density ratios (NP: BM -1:1, 1:2) for co-culture studies. Interestingly, in coculture conditions, the BM cell population declined in number while NP cells increased indicating that MSCs may in fact be signalling NP cells to proliferate rather than contributing to matrix formation. These findings provide exciting new insights on the potential of MSCs for NP tissue regeneration strategies.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Differential Response of Encapsulated Nucleus Pulposus and Bone Marrow Stem Cells in Isolation and Coculture in Alginate and Chitosan Hydrogels

Naqvi

Buckley

2015

Tissue Engineering Part A

View full text Add to dashboard Cite

show abstract

“…Previously, methods such as hypoxia treatment, use of 3-dimensional scaffolds, and coculturing were employed to induce MSCs' differentiation into NP-like cells. 10 – 13 Here, we used hypoxia and a 3D coculture system to test whether LFSCs can differentiate into NP-like cells. Coculturing with NPCs potently induced chondrogenic differentiation, as shown by the upregulated expression of collagen-II, aggrecan, and Sox-9.…”

mentioning

confidence: 99%

Differentiation of Human Ligamentum Flavum Stem Cells Toward Nucleus Pulposus-Like Cells Induced by Coculture System and Hypoxia

Han

Zhang

et al. 2015

Spine

View full text Add to dashboard Cite

Supplemental Digital Content is Available in the Text.We successfully selected ligamentum flavum stem cells and differentiated ligamentum flavum–derived stem cells demonstrating that coculture and hypoxia play an important part in differentiation. Moreover, we tested genes and protein levels that are considered as special marks of nucleus pulposus (NP). Interestingly, the data suggested that ligamentum flavum–derived stem cells were successfully differentiated into NP-like cells, which produced similar extracellular matrix as NP cells.

show abstract

“…[3573] without inducing an osteogenic phenotype and/or associated calcification or mineralization. [2443]…”

Section: Disc Regeneration Via Morphogens and Mitogensmentioning

confidence: 99%

Molecular and genetic advances in the regeneration of the intervertebral disc

Maerz

Herkowitz²,

Baker³

2013

Surg Neurol Int

View full text Add to dashboard Cite

Background:Owing to the debilitating nature of degenerative disc disease (DDD) and other spine pathologies, significant research has been performed with the goal of healing or regenerating the intervertebral disc (IVD). Structural complexity, coupled with low vascularity and cellularity, make IVD regeneration an extremely challenging task.Methods:Tissue engineering-based strategies utilize three components to enhance tissue regeneration; scaffold materials to guide cell growth, biomolecules to enhance cell migration and differentiation, and cells (autologous, or allogeneic) to initiate the process of tissue formation. Significant advances in IVD regeneration have been made utilizing these tissue engineering strategies.Results:The current literature demonstrates that members of the transforming growth factor beta (TGF-β) superfamily are efficacious in the regeneration of an anabolic response in the IVD and to facilitate chondrogenic differentiation. Gene therapy, though thwarted by safety concerns and the risk of ectopic transfection, has significant potential for a targeted and sustained regenerative response. Stem cells in combination with injectable, biocompatible, and biodegradable scaffolds in the form of hydrogels can differentiate into de novo IVD tissue and facilitate regeneration of the existing matrix. Therapies that address both anabolism and the inherent catabolic state of the IVD using either direct inhibitors or broad-spectrum inhibitors show extensive promise.Conclusion:This review article summarizes the genetic and molecular advances that promise to play an integral role in the development of new strategies to combat DDD and promote healing of injured discs.

show abstract

Modeling Nucleus Pulposus Regeneration In Vitro

Cited by 10 publications

References 10 publications

Differential Response of Encapsulated Nucleus Pulposus and Bone Marrow Stem Cells in Isolation and Coculture in Alginate and Chitosan Hydrogels

Differential Response of Encapsulated Nucleus Pulposus and Bone Marrow Stem Cells in Isolation and Coculture in Alginate and Chitosan Hydrogels

Differentiation of Human Ligamentum Flavum Stem Cells Toward Nucleus Pulposus-Like Cells Induced by Coculture System and Hypoxia

Molecular and genetic advances in the regeneration of the intervertebral disc

Contact Info

Product

Resources

About