Objective
To overcome the limitations of current islet cell transplantation technologies that require surgical steps and suffer from poor islet cell survival after transplation, this project aims to pre-condition a space for islet cell translation in the subcutaneous compartment that is connected to a vascularized blood supply. The team will develop a minimally invasive placeholder gel that calls in vascular connections and minimizes inflammation at the site, and then allows the non-surgical removal of the placeholder via a syringe. Cells can then be implanted through a minimally invasive, non-surgical placement of a islet cell encapsulation device or via injected islet cells directly into the pre-conditioned subcutaneous compartment site. This project is thus aimed at developing a placeholder platform that can generally serve patients who will benefit from islet cell transplantation treatments.
Background Rationale
Various methodologies have been developed to house cells within both device-based and device-less biological environments, aiming to enhance cellular survival and cell function post-transplantation. Particularly, the subcutaneous space has garnered interest due to its accessibility and potential for minimally invasive interventions. Among the promising approaches, prevascularized strategies are critical as they provide a supportive environment for rapid cell engraftment, sufficient oxygenation, and overall cell viability. Oxygen is crucial to prevent hypoxia immediately post-transplant, which is pivotal for maintaining the functional integrity of transplanted cells. However, these strategies face challenges such as concomitant tissue ingrowth with neoangiogenesis, which restricts the available space for cell placement after vasculature formation, necessitating the use of placeholders that can create a space for better cell transplantation. Traditional solid placeholders require invasive surgical removal, which risks damaging newly formed vasculature and may trigger an inflammatory response detrimental to cell engraftment. To overcome these limitations, we have developed and a new placeholder technology that allows removal by simply cooling the adjacent skin. This feature allows non-surgical removal of the placeholder via a syringe, significantly lowering the risk associated with surgical interventions and potentially improving therapeutic outcomes by enhancing and improving the local tissue environment to achieve better cell transplantation and subsequent function. This project will develop a placeholder platform that can generally serve patients who will benefit from islet cell transplantation treatments.
Description of Project
Technological advancements in cell encapsulation are set to advance islet transplantation for Type 1 diabetes (T1D) management for patients. Various methodologies have been developed to house cells within both device-based and device-less biological environments, aiming to enhance cellular survival and cell function post-transplantation. Particularly, the subcutaneous space has garnered interest due to its accessibility and potential for minimally invasive interventions. Among the promising approaches, prevascularized strategies are critical as they provide a supportive environment for rapid cell engraftment, sufficient oxygenation, and overall cell viability. Oxygen is crucial to prevent hypoxia immediately post-transplant, which is pivotal for maintaining the functional integrity of transplanted cells. However, these strategies face challenges such as concomitant tissue ingrowth with neoangiogenesis, which restricts the available space for cell placement after vasculature formation, necessitating the use of placeholders that can create a space for better cell transplantation. Traditional solid placeholders require invasive surgical removal, which risks damaging newly formed vasculature and may trigger an inflammatory response detrimental to cell engraftment. To overcome these limitations, we have developed and a new placeholder technology that allows removal by simply cooling the adjacent skin. This feature allows non-surgical removal of the placeholder via a syringe, significantly lowering the risk associated with surgical interventions and potentially improving therapeutic outcomes by enhancing and improving the local tissue environment to achieve better cell transplantation and subsequent function. This project will develop the new placeholders for both a device that has been developed for cell transplantation, and for a device-less technology. This project is thus aimed at developing a placeholder platform that can generally serve patients who will benefit from islet cell transplantation treatments.
Anticipated Outcome
This technology not only promises to improve therapeutic outcomes but also aligns with the ongoing shift towards less invasive medical procedures, to set new standard in the islet cell treatment paradigm for T1D. The project will optimize the mechanical stability of the placeholder for both islet cell encapsulation devices, and directly in the subcuataneous tissue for islet cell injection technologies. The placeholders will further have optimized designs to call in vascular connections that precondition the local environment to supply critical oxygen and nutrient supplies. Finally, the placeholders will be optimized to for biodegradability and biocompatibility, to allow rapid non-surgical removal while maintaining a cell-friendly environment that allows optimal islet cells survival and function after subsequent transplantation. At the end of the project these lead placeholder designs would be ready for pre-clinical development with industry-support towards first-in-human safety and efficacy translation.
Relevance to T1D
Islet cell transplantation is aimed at creating a biological solution to diabetes, providing a mechanism for controlled insulin production that takes away the need for measuring glucose, delivering insulin through pumps or injections, and providing patients with a life free from these daily therapy interventions. If successful, this project would develop a preconditioning technology to enhance the transplantation of the insulin-producing beta cells into the subcutaneous compartment rather without requiring a surgical intervention or the traditional portal vein and liver transplantation route. By preconditioning and pre-connecting a vascular supply at the subcutaneous transplantation site, patients would achieve a more functional islet cell translation that could lengthen the duration of beta cell insulin production, while also being less invasive and less painful as a cell transplantation procedure.