title: CRISPR-targeted genome editing of mesenchymal stem cell-derived therapies for type 1 diabetes: a path to clinical success?
abstract: Due to their ease of isolation, differentiation capabilities, and immunomodulatory properties, the therapeutic potential of mesenchymal stem cells (MSCs) has been assessed in numerous pre-clinical and clinical settings. Currently, whole pancreas or islet transplantation is the only cure for people with type 1 diabetes (T1D) and, due to the autoimmune nature of the disease, MSCs have been utilised either natively or transdifferentiated into insulin-producing cells (IPCs) as an alternative treatment. However, the initial success in pre-clinical animal models has not translated into successful clinical outcomes. Thus, this review will summarise the current state of MSC-derived therapies for the treatment of T1D in both the pre-clinical and clinical setting, in particular their use as an immunomodulatory therapy and targets for the generation of IPCs via gene modification. In this review, we highlight the limitations of current clinical trials of MSCs for the treatment of T1D, and suggest the novel clustered regularly interspaced short palindromic repeat (CRISPR) gene-editing technology and improved clinical trial design as strategies to translate pre-clinical success to the clinical setting.
authors.affiliation: The School of Life Sciences, Chronic Disease Solutions Team and the Centre for Health Technologies, University of Technology Sydney, PO Box 123, Broadway, NSW, 2007, Australia.
authors.forename: Dario
authors.initials: D
authors.lastname: Gerace
authors.affiliation: The School of Life Sciences, Chronic Disease Solutions Team and the Centre for Health Technologies, University of Technology Sydney, PO Box 123, Broadway, NSW, 2007, Australia.|Translational Cancer Research Group, University of Technology Sydney, Sydney, Australia.
authors.forename: Rosetta
authors.initials: R
authors.lastname: Martiniello-Wilks
authors.affiliation: The School of Life Sciences, Chronic Disease Solutions Team and the Centre for Health Technologies, University of Technology Sydney, PO Box 123, Broadway, NSW, 2007, Australia.
authors.forename: Najah Therese
authors.initials: NT
authors.lastname: Nassif
authors.affiliation: The School of Life Sciences, Chronic Disease Solutions Team and the Centre for Health Technologies, University of Technology Sydney, PO Box 123, Broadway, NSW, 2007, Australia.|Neuroscience Research Unit, University of Technology Sydney, Sydney, Australia.
authors.forename: Sara
authors.initials: S
authors.lastname: Lal
authors.affiliation: The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, Australia.
authors.forename: Raymond
authors.initials: R
authors.lastname: Steptoe
authors.affiliation: The School of Life Sciences, Chronic Disease Solutions Team and the Centre for Health Technologies, University of Technology Sydney, PO Box 123, Broadway, NSW, 2007, Australia. Ann.Simpson@uts.edu.au.
authors.forename: Ann Margaret
authors.initials: AM
authors.lastname: Simpson
mesh_terms: D064113:CRISPR-Cas Systems / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000072669:Gene Editing; D015316:Genetic Therapy; D006801:Humans; D007515:Islets of Langerhans / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology
keywords: Clinical trials; Immunomodulation; Insulin-producing cells; Mesenchymal stem cells; Type 1 diabetes