Light bulb moments: bioluminescence in T1D research

Light bulb moments: bioluminescence in T1D research

By: Shruthi Kandalai

Epigenetic changes, or changes made to DNA expression without altering the genes themselves, have been thought to affect various disease states, including T1D. A recent review looked into using in vivo bioluminescence imaging to more easily study epigenetics and changes to immune function.

  • By using a luciferase (bioluminescent enzyme) reporter, researchers were able to track cells in freely moving animals, including those related to transplants and immune function.
  • Bioluminescence has also been used to study epigenetic changes in vivo to see how environmental factors affect gene expression as well as  to track immune cell subgroups to better understand how the immune system responds to diseases.
  • Unlike other methods of fluorescent imaging, bioluminescent imaging requires no external illumination and has a higher signal-to-noise ratio.

This work may point to a future direction to study epigenetic and immune changes for T1D research.

This research on using bioluminescence to study epigenetic and immune changes also builds off the current use of bioluminescence in T1D research, where the focus has been related to islet cell transplants.

  • To study how the immune system can lead to graft destruction and impairment of insulin secretion, a research group transplanted nude mice with MIN6 (mouse insulinoma β cell line) to mimic pancreatic islet transplantation. The cell line also constitutively expressed luciferase, so that the cells could be tracked noninvasively following engraftment.
    • Results showed that bioluminescence decreased in line with the loss of MIN6 cells during the first few days of implantation and that bioluminescence increased a week after implantation when MIN6 cells became integrated with host vasculature.
  • Another study focused on bioluminescence signaling and how well it could detect cells in in vitro experiments.
    • Results showed that there was a linear correlation between signal intensity and viable cells.
    • Bioluminescence signaling could successfully detect transduction of cells.
    • There needed to be a minimum number of viable cells present for any bioluminescent signal to be detected, so areas with few viable cells did not give off signals that could be detected..
  • A recent paper also studied bioluminescence of islet transplants in rats.
    • Results showed that while the bioluminescent signals were present when the transplant first took place, the signals fell sharply after the first two months.
    • Signals were much higher in rats that experienced diabetes reversal following transplant, than those that did not, suggesting that signal strength could be indicative of cell survival.
    • While associated with survival of the transplanted cells, changes in bioluminescence were not directly proportional to the viability of the graft.

Overall, these studies show how bioluminescent imaging can be used both in in vivo and in vitro populations, while also revealing some of the limitations that may come with bioluminescence imaging that would need to be considered in future experiments using similar processes for studying immune cells or epigenetics.

The takeaway: A new paper using bioluminescence to study epigenetic changes and immune cell function may be a future path for T1D research. This paper also builds off of previous work using bioluminescent imaging in T1D research.

Sources:

  • Dimond, A., Pette, M. V., & Fisher, A. G. (2020). Illuminating Epigenetics and Inheritance in the Immune System with Bioluminescence. Trends in Immunology, 41(11), 994-1005.
  • Yu, C., Juang, J., Lin, Y., Kuo, C., Hsieh, L., & Huang, C. (2020). Enhancement of Subcutaneously Transplanted β Cell Survival Using 3D Stem Cell Spheroids with Proangiogenic and Prosurvival Potential. Advanced Biosystems, 4(3).
  • Liang, S., Louchami, K., Holvoet, B., Verbeke, R., Deroose, C. M., Manshian, B., . . . Himmelreich, U. (2018). Tri-modal In vivo Imaging of Pancreatic Islets Transplanted Subcutaneously in Mice. Molecular Imaging and Biology, 20(6), 940-951.
  • Komatsu, H., Gonzalez, N., Ortiz, J., Rawson, J., Omori, K., Kandeel, F., & Mullen, Y. (2020). Early-Phase Luciferase Signals of Islet Grafts Predicts Successful Subcutaneous Site Transplantation in Rats. Molecular Imaging and Biology.

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