Graduation Semester and Year
Summer 2025
Language
English
Document Type
Dissertation
Degree Name
Doctor of Philosophy in Biomedical Engineering
Department
Bioengineering
First Advisor
Michael Cho
Abstract
Islet transplantation is a potential therapeutic route for type 1 diabetic patients facing chronic ketoacidosis and/or hypoglycemia unable to be properly regulated with standard insulin administration. However, successful engraftment is hampered by a multitude of factors. Harvested islets face rapid, substantial degradation due to hypoxia and nutrient depletion once isolated. Transplanted islets are additionally susceptible to the instant blood-mediated inflammatory reaction (IBMIR). This combination of factors leads to more than half of transplanted islets failing to engraft post-surgery. Many areas of research are dedicated to investigating alternative approaches or supplemental treatments to improve the success rate of engraftment and insulin independence. This research examines the use of low-level laser therapy, known as photobiomodulation (PBM), as a potential modality for enhancing the functionality of islets.
PBM utilizes near-infrared (NIR) light to stimulate mitochondrial activity and increase ATP synthesis. Augmented ATP production facilitates greater influx of extracellular calcium into pancreatic β-cells, triggering enhanced insulin exocytosis. Analysis of calcium dynamics in individual pancreatic cell lines was streamlined through the creation of a computer vision pipeline for end-to-end segmentation, tracking, and calcium spike detection. This automated system increased the accuracy and efficiency of segmentation and data management, while simultaneously reducing bias and time of analysis, allowing for more robust examination of calcium response to photostimulation. The success of PBM largely depends on parameter optimization, which tends to be cell-type dependent. Ideal PBM settings for stimulating calcium activity in islets are yet to be fully elucidated. However, a wavelength of 810 nm and fluence of 9 J/cm2 have demonstrated positive outcomes. Specific irradiance, exposure rate, and pulse mode still warrant further investigation.
We further sought to evaluate the effects of PBM on pancreatic islets, as they make up the source of donor tissue for transplantation. Increased insulin secretion and mitochondrial activity was successfully replicated in harvested mouse islets. Insulin concentration in photostimulated islets was highest 72 hours post-isolation, making this the ideal timeframe for transplantation. Thus, PBM has demonstrated its ability to enhance functionality in islets, broadening the scope of prospective therapeutics for diabetes.
Keywords
Photobiomodulation, Insulin secretion, Beta cell physiology, Calcium dynamics, Islet transplantation, Image analysis, Computer vision algorithms
Disciplines
Biomedical Engineering and Bioengineering
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Fowlds, Kelli, "Functional Enhancement of Pancreatic Islets through Photobiomodulation for Potential Diabetes Therapeutics" (2025). Bioengineering Dissertations. 204.
https://mavmatrix.uta.edu/bioengineering_dissertations/204