Periodic Reporting for period 3 - ECaBox (ECaBox "Eyes in a Care Box": Regenerating human retina from resuscitated cadaveric eyes)
Okres sprawozdawczy: 2024-03-01 do 2025-08-31
Retinal degenerations are a leading cause of sight loss and blindness worldwide and are most often not curable, and preclinical research lacks adequate models of human organs. Although in the last decade basic and translational research expanded the development of new treatments, numerous potential therapies end up in the “valley of death” and additional methods are needed to support new therapeutic interventions. Alternative approaches such as human organoids are a major step forward in mimicking physiological conditions but they fail to reflect the overall tissue and organ complexity. Explanted human eyes can currently be kept, before going through massive and irreversible damage, for a time that is too short to serve as testbed. To address this need, a consortium of 7 partners across Europe has developed a revolutionary platform, the ECaBox (Eyes in a Care Box), to resuscitate human cadaveric eyes. The project has designed a pioneering device to preserve the human eye and guarantee retina function and structure ex vivo for an extended time period. This new technology will circumvent ethical restrictions linked to human experimentation and reduce the need for animal testing, providing a ground breaking advancement in assessing the efficacy and safety of regenerative therapies. The project aims to serve as proof of concept for organ preservation ex vivo and how the new approach can accelerate the development of new therapies, transforming the organ transplantation field.
Since the start of the project, a robust protocol for eye cannulation and perfusion was established in pig and replicated in human eyes. This is a pivotal step in the development of the ECaBox, as eye perfusion is key to provide blood circulation into the organ and a fast procedure is crucial to prevent tissue degeneration. Images of the eye circulatory system were acquired and used to model a vascular anatomic reconstruction to support development of the perfusion system within ECaBox. Very interesting results were also achieved from a technological point of view: studies of the physiological vitreous humour led to the initial definition of an artificial replacement material; a preliminary submersion media compatible with maintenance of a viable human eye was formulated; extensive research went into looking for a suitable oxygen carrier to be used as blood substitute for the eye perfusion. Additionally, the consortium worked on the development of a portable system for continuous functional monitoring of the eye to assess retinal viability, and tested it on ex vivo eyes. Importantly, the consortium developed a prototype that enabled perfusion and resuscitation of ex vivo eyes under defined conditions. Preliminary outcomes support the feasibility of post-mortem ocular support using our first-of-its-kind ECaBox system. In parallel, the eye-on-chip technology deployed within the project promises exciting opportunities for additional research as it can help build up essential knowledge to be translated into new therapeutic approaches. Another advance was the demonstration that human retinal stem cells can fuse with adult stem cells and that the resulting hybrids have the potential to differentiate, indicating that cell fusion-mediated therapy is a potential regenerative approach for treating human retinal dystrophies. Transversally, the consortium established a general workflow on exploitable innovations and broadly reached out to relevant stakeholders and the general public promoting their engagement.
Developing the ECaBox involves overcoming important scientific and technical challenges since there are no current systems available to set advanced eye perfusion nor to create artificial human fluids to resuscitate organ function. ECaBox constitutes a major milestone supporting physiological eye function ex vivo for extended periods and represents a radical advance in the regenerative restoration of human organs. It promises to have a great impact on health and society through its use in regenerative medicine, in the development of cell, drug, and gene therapies as well as for organ preservation and transplantation.
Foundation of new translational research technologies
The reactivated developmental programs that lower vertebrates use to regrow a functional organ inspire regenerative medicine. Cell-based therapies have already revolutionized several aspects of modern medicine and it is widely accepted that regenerative approaches have a disruptive potential to innovate health care. However, pioneering technologies are needed to support the translation of basic research into therapeutic realities. ECaBox will have a huge impact in advancing regenerative medicine by providing an intact human organ ex vivo. The medical need for novel therapeutic strategies for blindness is enormous as current treatments are limited in scope and often do not offer curative solutions. Thus, the ECaBox helps tackle several challenges and produce:
• Novel technology to test emerging treatments.
• More predictive pre-clinical studies at significantly reduced costs. This will allow more drug candidates and approaches to be tested faster and more reliably.
• Technology expandable to other neurodegenerative diseases and ex vivo organ systems.
• Novel knowhow and technologies to support the competitiveness of European industry in regenerative medicine.
Social and economic impact of retinal regeneration
Impaired vision affects over 250 million people worldwide and 36 million are blind. As retinal degenerations are often not curable, due to the increase in the ageing population vision loss will have a major impact on individuals, families, communities, and nations unless cost-effective curative treatments become available. The market of ophthalmic drugs was $30 billion in 2016, and it is growing at a fast pace. Any new drug has to recover several billion in a time span limited by the patent duration and competing drugs on the market. Improved productivity of the drug development process by providing access to valuable human tissue with the ECaBox holds great potential not only in cost savings, but also to unleash modern translational research capabilities onto new disease areas. Further research on ECaBox will contribute to lowering the investment required for each drug reaching the market, additionally decreasing the use of animals in preclinical research.
Building leading research and innovation capacity across Europe
ECaBox has integrated current expertise in regenerative medicine at the frontier of different disciplines such as biomaterial science, stem cell biology, electrophysiology, chemical and material engineering, computational biology and modelling. Moreover, the ECaBox consortium has trained PhD students and researchers in a fertile and highly interdisciplinary innovation environment to become future technology leaders prepared to overcome the current challenges in translating basic research such as stem cell differentiation into regenerative therapies.
Foundation of new translational research technologies
The reactivated developmental programs that lower vertebrates use to regrow a functional organ inspire regenerative medicine. Cell-based therapies have already revolutionized several aspects of modern medicine and it is widely accepted that regenerative approaches have a disruptive potential to innovate health care. However, pioneering technologies are needed to support the translation of basic research into therapeutic realities. ECaBox will have a huge impact in advancing regenerative medicine by providing an intact human organ ex vivo. The medical need for novel therapeutic strategies for blindness is enormous as current treatments are limited in scope and often do not offer curative solutions. Thus, the ECaBox helps tackle several challenges and produce:
• Novel technology to test emerging treatments.
• More predictive pre-clinical studies at significantly reduced costs. This will allow more drug candidates and approaches to be tested faster and more reliably.
• Technology expandable to other neurodegenerative diseases and ex vivo organ systems.
• Novel knowhow and technologies to support the competitiveness of European industry in regenerative medicine.
Social and economic impact of retinal regeneration
Impaired vision affects over 250 million people worldwide and 36 million are blind. As retinal degenerations are often not curable, due to the increase in the ageing population vision loss will have a major impact on individuals, families, communities, and nations unless cost-effective curative treatments become available. The market of ophthalmic drugs was $30 billion in 2016, and it is growing at a fast pace. Any new drug has to recover several billion in a time span limited by the patent duration and competing drugs on the market. Improved productivity of the drug development process by providing access to valuable human tissue with the ECaBox holds great potential not only in cost savings, but also to unleash modern translational research capabilities onto new disease areas. Further research on ECaBox will contribute to lowering the investment required for each drug reaching the market, additionally decreasing the use of animals in preclinical research.
Building leading research and innovation capacity across Europe
ECaBox has integrated current expertise in regenerative medicine at the frontier of different disciplines such as biomaterial science, stem cell biology, electrophysiology, chemical and material engineering, computational biology and modelling. Moreover, the ECaBox consortium has trained PhD students and researchers in a fertile and highly interdisciplinary innovation environment to become future technology leaders prepared to overcome the current challenges in translating basic research such as stem cell differentiation into regenerative therapies.