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.

Effect of Stem Cells and Gene Transfected Stem Cells Therapy on the Pancreas of Experimentally Induced Type 1 Diabetes

“…The previous results indicated regression of induced diabetic degenerative changes by AMSCs therapy. This outcome was concomitant with Gerace et al (35), who documented that MSC interventions demonstrated improved T1DM outcomes through MSC migration to areas of pancreatic injury. In addition, MSCs modify the islet microenvironment to promote the survival and regeneration of surviving β cells and abrogate inherent autoimmunity against β cells.…”

Comparative Histological Study on the Effect of Stem Cells, and Gene Modified Stem Cells in Experimentally-Induced Diabetes Type 1 Cardiomyopathy

“…It was proved that mesenchymal stem cells modify the tissue microenvironment and promote the survival and regeneration of beta cell mass which controls the glycemic state more efficiently [40] .…”

Tooth Regeneration: Insights from Tooth Development and Spatial-Temporal Control of Bioactive Drug Release

“…Due to safety concern about dissemination of the gene vectors and their adverse side-effect in non-target sites, a direct injection of the expression vector was used less than an indirect injection of cells injection. Genetically modified cell transplantation technology has been widely applied to the research of gene therapy in vitro and in vivo for many human diseases, such as junctional epidermolysis bullosa [124], metastatic cancer [125], type 1 diabetes [126]. As mentioned above, the process of tissue regeneration is regulated spatialtemporally by a variety of cytokines.…”