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Bone & Joint Research
Vol. 9, Issue 7 | Pages 351 - 359
1 Jul 2020
Fitzgerald J

The ability to edit DNA at the nucleotide level using clustered regularly interspaced short palindromic repeats (CRISPR) systems is a relatively new investigative tool that is revolutionizing the analysis of many aspects of human health and disease, including orthopaedic disease. CRISPR, adapted for mammalian cell genome editing from a bacterial defence system, has been shown to be a flexible, programmable, scalable, and easy-to-use gene editing tool. Recent improvements increase the functionality of CRISPR through the engineering of specific elements of CRISPR systems, the discovery of new, naturally occurring CRISPR molecules, and modifications that take CRISPR beyond gene editing to the regulation of gene transcription and the manipulation of RNA. Here, the basics of CRISPR genome editing will be reviewed, including a description of how it has transformed some aspects of molecular musculoskeletal research, and will conclude by speculating what the future holds for the use of CRISPR-related treatments and therapies in clinical orthopaedic practice.

Cite this article: Bone Joint Res 2020;9(7):351–359.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_16 | Pages 76 - 76
1 Nov 2018
Fitzgerald J Shaw G Coleman C Barry F
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Clinical translation of MSC therapies in orthopaedics has been hampered by heterogeneity and a lack of standardised and validated testing protocols for quality assurance. Although minimal criteria have been proposed1, it is apparent that these do not predict performance in vivo. We used a combinatorial antibody profiling tool to probe the surface immunophenotype of human bone marrow derived MSCs and used this to define new marker panels. Cells were cultured from three marrow donors using specified expansion conditions and probed by high throughput flow cytometry using a panel of 230 antibodies. Analysis of expression of the surface proteins revealed significant variation in response to culture conditions and considerably less variation between donors. Of the panel of 230 markers 107 were negative, 24 had high expression in all samples, 1 had low expression and 98 displayed significant differences between cell preparations. Cluster analyses revealed that marker expression in one culture condition varied considerably from the other two. Phenotypic characterization of the cell preparations, assessed by analysis of differentiation propensity, showed similar patterns of variability between these samples. This suggests that the selected panel may be used as phenotypic MSC markers. Ongoing work involves the generation of novel antibody arrays which will be used as quality tests in a manufacturing environment. These tests will be used for in-process and product release applications for enhanced cell manufacturing and improved clinical outcomes.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 11 | Pages 1413 - 1420
1 Nov 2007
FitzGerald J Fawcett J

The subject of central nervous system damage includes a wide variety of problems, from the slow selective ‘picking off’ of characteristic sub-populations of neurons typical of neurodegenerative diseases, to the wholesale destruction of areas of brain and spinal cord seen in traumatic injury and stroke. Experimental repair strategies are diverse and the type of pathology dictates which approach will be appropriate. Damage may be to grey matter (loss of neurons), white matter (cutting of axons, leaving neurons otherwise intact, at least initially) or both. This review will consider four possible forms of treatment for repair of the human central nervous system.


The Journal of Bone & Joint Surgery British Volume
Vol. 58-B, Issue 2 | Pages 184 - 192
1 May 1976
Fitzgerald J Newman P

A clinical study has been made of forty-three patients with symptoms arising from degenerative spondylolisthesis of the lumbar spine. Attention is drawn to the lower average level of the iliac crests in these patients, and to the high incidence of osteoarthritis of the hips. Many patients in this series had been referred specifically for operation and fourteen were so treated. The techniques of decompression and of spinal fusion are discussed. It is concluded that patients with back pain predominant are well treated by corsetry, only a minority needing fusion, and that patients with nerve root involvement or with symptoms of spinal stenosis need decompression. The place of spinal fusion is the main problem, but it seems reasonable, firstly, in younger patients with clear evidence of instability and degenerative change at a single level, and secondly, when radical decompression is judged to increase the risk of instability.