ORCID Profile
0000-0003-4489-7107
Current Organisation
The University of Sheffield - The Edge
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Publisher: Wiley
Date: 09-07-2023
DOI: 10.1002/JSP2.1272
Abstract: Lineage‐tracing experiments have established that the central region of the mature intervertebral disc, the nucleus pulposus (NP), develops from the embryonic structure called “the notochord”. However, changes in the cells derived from the notochord which form the NP (i.e., notochordal cells [NCs]), in terms of their phenotype and functional identity from early developmental stages to skeletal maturation are less understood. These key issues require further investigation to better comprehend the role of NCs in homeostasis and degeneration as well as their potential for regeneration. Progress in utilizing NCs is currently h ered due to poor consistency and lack of consensus methodology for in vitro NC extraction, manipulation, and characterization. Here, an international group has come together to provide key recommendations and methodologies for NC isolation within key species, numeration, in vitro manipulation and culture, and characterization. Recommeded protocols are provided for isolation and culture of NCs. Experimental testing provided recommended methodology for numeration of NCs. The issues of cryopreservation are demonstrated, and a pannel of immunohistochemical markers are provided to inform NC characterization. Together we hope this article provides a road map for in vitro studies of NCs to support advances in research into NC physiology and their potential in regenerative therapies.
Publisher: Wiley
Date: 08-10-2018
DOI: 10.1002/JSP2.1036
Publisher: Wiley
Date: 28-11-2022
DOI: 10.1002/JSP2.1235
Abstract: Intervertebral disc degeneration is a common cause of low back pain, the leading cause of disability worldwide. Appropriate preclinical models for intervertebral disc research are essential to achieving a better understanding of underlying pathophysiology and for the development, evaluation, and translation of more effective treatments. To this end, in vivo animal and ex vivo organ culture models are both widely used by spine researchers however, the relative strengths and weaknesses of these two approaches are a source of ongoing controversy. In this article, members from the Spine and Preclinical Models Sections of the Orthopedic Research Society, including experts in both basic and translational spine research, present contrasting arguments in support of in vivo animal models versus ex vivo organ culture models for studies of the disc, supported by a comprehensive review of the relevant literature. The objective is to provide a deeper understanding of the respective advantages and limitations of these approaches, and advance the field toward a consensus with respect to appropriate model selection and implementation. We conclude that complementary use of several model types and leveraging the unique advantages of each is likely to result in the highest impact research in most instances.
Publisher: Wiley
Date: 02-08-2018
DOI: 10.1002/JSP2.1027
Publisher: The Company of Biologists
Date: 2019
DOI: 10.1242/DMM.038042
Abstract: Extensive loss of dopaminergic neurons, and aggregation of the protein α-synuclein into ubiquitin-positive Lewy bodies represents a major neuropathological hallmark of Parkinson's disease. At present the generation of large nuclear-associated Lewy bodies from endogenous wild-type α-synuclein, translationally regulated under its own promoter in human cell culture models requires costly and time-consuming protocols. Here, we demonstrate that fully differentiated human SH-SY5Y neuroblastoma cells grown in three-dimensional cell culture develop Lewy body-like pathology upon exposure to exogenous α-synuclein species. In contrast to most cell- and rodent-based models that exhibit multiple diffuse α-synuclein aggregates throughout the cytoplasm, a single large nuclear inclusion immuno-positive for α-synuclein and ubiquitin is rapidly obtained in our model. This was achieved, without the need for over-expression of α-synuclein or genetic modification of the cell line. However, phosphorylation of α-synuclein within these inclusions was not observed. The system described here provides an ideal tool to screen compounds to therapeutically intervene in Lewy body formation and to investigate the mechanisms involved in disease progression in synucleinopathies.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Christine Le Maitre.