Government of Canada and JDRF Canada Announce New Research Funding to Accelerate Stem Cell-Based Therapies for Type 1 Diabetes

To mark the end of Diabetes Awareness Month, Sonia Sidhu, Member of Parliament for Brampton South, on behalf of the Honourable Patty Hajdu, Minister of Health, announced an investment of $6 million through the CIHR-JDRF Partnership to Defeat Diabetes for two Canadian research teams to accelerate the development of stem cell-based therapies for the treatment of type 1 diabetes.
[Juvenile Diabetes Research Foundation]
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Mitophagy Protects Beta Cells from Inflammatory Damage in Diabetes

Mitophagy-deficient β-cells were sensitized to inflammatory stress, leading to the accumulation of fragmented dysfunctional mitochondria, increased β-cell death, and hyperglycemia.
[JCI Insight]
Sidarala, V., Pearson, G. L., Parekh, V. S., Thompson, B., Christen, L., Gingerich, M. A., Zhu, J., Stromer, T., Ren, J., Reck, E. C., Chai, B., Corbett, J. A., Mandrup-Poulsen, T., Satin, L. S., & Soleimanpour, S. A. (2020). Mitophagy protects beta cells from inflammatory damage in diabetes. JCI Insight. https://doi.org/10.1172/jci.insight.141138 Cite
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Butyrate Induced Tregs are Capable of Migration from the GALT to the Pancreas to Restore Immunological Tolerance during Type-1 Diabetes

Scientists investigated the mechanism of diabetes remission in non-obese diabetic mice following butyrate administration.
[Scientific Reports]
Jacob, N., Jaiswal, S., Maheshwari, D., Nallabelli, N., Khatri, N., Bhatia, A., Bal, A., Malik, V., Verma, S., Kumar, R., & Sachdeva, N. (2020). Butyrate induced Tregs are capable of migration from the GALT to the pancreas to restore immunological tolerance during type-1 diabetes. Scientific Reports, 10(1), 19120. https://doi.org/10.1038/s41598-020-76109-y Cite
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Human T Cells Expressing a CD19 CAR-T Receptor Provide Insights into Mechanisms of Human CD19-Positive β Cell Destruction

Coculturing CD19-expressing β-like cells and CD19 CAR-T cells resulted in T cell-mediated β-like cell death with release of activated T cell cytokines.
[Cell Reports Medicine]
Ma, H., Jeppesen, J. F., & Jaenisch, R. (2020). Human T Cells Expressing a CD19 CAR-T Receptor Provide Insights into Mechanisms of Human CD19-Positive β Cell Destruction. Cell Reports Medicine, 1(6). https://doi.org/10.1016/j.xcrm.2020.100097 Cite
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Overexpression of Alpha-1 Antitrypsin in Mesenchymal Stromal Cells Improves their Intrinsic Biological Properties and Therapeutic Effects in Nonobese Diabetic Mice

Based on the anti‐inflammatory effects of alpha‐1 antitrypsin (AAT), scientists generated human AAT engineered MSCs by infecting human bone marrow‐derived MSCs with the pHAGE CMV‐a1aT‐UBC‐GFP‐W lentiviral vector.
[Stem Cells Translational Medicine]
Song, L., Gou, W., Wang, J., Wei, H., Lee, J., Strange, C., & Wang, H. (n.d.). Overexpression of alpha-1 antitrypsin in mesenchymal stromal cells improves their intrinsic biological properties and therapeutic effects in nonobese diabetic mice. STEM CELLS Translational Medicine, n/a(n/a). https://doi.org/10.1002/sctm.20-0122 Cite
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Integration of Islet/Beta-Cell Transplants with Host Tissue using Biomaterial Platforms

This review discusses the various scaffold platforms and design parameters that have been identified for the manufacture of hPSC-derived β-cells, and the transplantation of islets/β-cells to maintain normal blood glucose levels
[Endocrinology]
Clough, D. W., King, J. L., Li, F., & Shea, L. D. (n.d.). Integration of islet/beta-cell transplants with host tissue using biomaterial platforms. Endocrinology. https://doi.org/10.1210/endocr/bqaa156 Cite
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Circulating Unmethylated CHTOP and INS DNA Fragments Provide Evidence of Possible Islet Cell Death in Youth with Obesity and Diabetes

The authors identified the CHTOP gene as a candidate whose CpGs show a greater frequency of unmethylation in human islets. A digital PCR strategy was used to determine the methylation pattern of CHTOP and INS CpG sites in primary human tissues.
[Clinical Epigenetics]
Circulating unmethylated CHTOP and INS DNA fragments provide evidence of possible islet cell death in youth with obesity and diabetes | Clinical Epigenetics | Full Text. (n.d.). Retrieved August 11, 2020, from https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-020-00906-5 Cite
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Follicular Helper T Cell Profiles Predict Response to Costimulation Blockade in Type 1 Diabetes

Unbiased bioinformatics analysis identified that inducible costimulatory molecule (ICOS)+ folliular helper T cells and other ICOS+ populations, including peripheral helper T cells, were highly sensitive to costimulation blockade.
[Nature Immunology]
Edner, N. M., Heuts, F., Thomas, N., Wang, C. J., Petersone, L., Kenefeck, R., Kogimtzis, A., Ovcinnikovs, V., Ross, E. M., Ntavli, E., Elfaki, Y., Eichmann, M., Baptista, R., Ambery, P., Jermutus, L., Peakman, M., Rosenthal, M., & Walker, L. S. K. (2020). Follicular helper T cell profiles predict response to costimulation blockade in type 1 diabetes. Nature Immunology, 1–12. https://doi.org/10.1038/s41590-020-0744-z Cite
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Genome-Scale In Vivo CRISPR Screen Identifies RNLS as a Target for Beta Cell Protection in Type 1 Diabetes

Using a genome-scale CRISPR screen in a mouse model for type 1 diabetes (T1D), researchers showed that deleting RNLS, a genome-wide association study candidate gene for T1D, made beta cells resistant to autoimmune killing.
[Nature Metabolism]
Cai, E. P., Ishikawa, Y., Zhang, W., Leite, N. C., Li, J., Hou, S., Kiaf, B., Hollister-Lock, J., Yilmaz, N. K., Schiffer, C. A., Melton, D. A., Kissler, S., & Yi, P. (2020). Genome-scale in vivo CRISPR screen identifies RNLS as a target for beta cell protection in type 1 diabetes. Nature Metabolism, 1–12. https://doi.org/10.1038/s42255-020-0254-1 Cite
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Modeling Type 1 Diabetes In Vitro Using Human Pluripotent Stem Cells

Investigators describe an in vitro platform that modeled features of human type 1 diabetes using stress-induced patient-derived endocrine cells and autologous immune cells.
[Cell Reports]
Leite, N. C., Sintov, E., Meissner, T. B., Brehm, M. A., Greiner, D. L., Harlan, D. M., & Melton, D. A. (2020). Modeling Type 1 Diabetes In Vitro Using Human Pluripotent Stem Cells. Cell Reports, 32(2). https://doi.org/10.1016/j.celrep.2020.107894 Cite
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Current Progress in Stem Cell Therapy for Type 1 Diabetes Mellitus

Researchers discuss the current research advances in strategies to obtain insulin-producing cells from different precursor cells and in stem cell-based therapies for diabetes.
[Stem Cell Research & Therapy]
Chen, S., Du, K., & Zou, C. (2020). Current progress in stem cell therapy for type 1 diabetes mellitus. Stem Cell Research & Therapy, 11(1), 275. https://doi.org/10.1186/s13287-020-01793-6 Cite
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