Objective
The general objective of this proposal is to develop a non-invasive oxygen-sensing material for localized monitoring of vascular remodeling in β-cells at alternative implant sites. This material will emit an optical signal that can be used to generate a predictive score for transplantation outcomes. This innovative tool will enable point-of-care monitoring, allowing for patient stratification and early interventions to preserve graft function.
Background Rationale
Beta-cell replacement has proven an effective approach in restoring euglycemia in type 1 diabetic patients. Despite the clinical success, commercialization of beta-cell products is still challenged by multiple challenges including the lack of non-invasive graft monitoring to assess the potency of the cells after delivery. Thus, the development of a non-invasive tool for tracking revascularization, and its subsequent implementation as a quantitative score to predict transplant outcomes will offer a unique tool for early therapeutic management that can limit cell metabolic burnout and promote long-term graft survival and function.
Description of Project
A significant challenge to the clinical implementation of cell therapies, despite their proven success in restoring insulin independence, is the absence of non-invasive tools for longitudinal in vivo monitoring of cellular revascularization and engraftment. Current in vivo beta-cell monitoring strategies largely depend on manipulating the beta-cell product before implantation, the uptake of contrast agents by the cells in vivo, and the use of costly instrumentation, all of which limit accessibility and potentially affect cell viability. To address this, we aim to develop a tool for non-invasive longitudinal in vivo monitoring of oxygenation, serving as an indicator of the vascular network's adequacy in supporting beta-cell grafts. Furthermore, we plan to utilize AI techniques to create a quantitative graft vascular network quality index (GVNQI) score. This effort aims to enhance clinical outcomes and support the commercialization of beta-cell replacement therapies.
Anticipated Outcome
We anticipate generating a comprehensive understanding of the relationship between biomaterial-mediated vascularization, tissue oxygen tension, and beta-cell viability in vivo. This will allow for the noninvasive assessment of vascularization through oxygenation monitoring, optimization of transplant conditions, and the development of superior strategies to enhance vascular growth, ultimately improving overall transplantation outcomes.
Relevance to T1D
This project holds significant importance for the T1D community, as a non-invasive tool for monitoring cellular therapies will enable timely interventions to preserve beta-cell function. Furthermore, it will facilitate the development of enhanced revascularization strategies based on real-time biological signals. We hypothesize that non-invasive monitoring of graft viability will improve the safety and clinical applicability of these strategies.