Human tissue models for lung disease

Lead Research Organisation: Imperial College London
Department Name: National Heart and Lung Institute

Abstract

More research is required to identify effective and safe therapeutics for the treatment of lung diseases such as asthma and chronic obstructive pulmonary disease. Much of the research effort currently is carried out in animal models. However, because diseases such as asthma are a uniquely human condition it is sometimes difficult to interpret data generated in animal models and apply the knowledge gained in a logical way to the human disease process. A recent survey identified a need to use fresh human tissue samples for lung research. The major obstacle to obtaining tissues of this sort appears to be the lack of infrastructure and process for distributing the human tissue were consent has been given for deceased donor tissue to be used for research. Currently a significant amount of human tissue is being disposed of in hospitals all over the country. A strategic collaboration between academics and the National Health Service Blood and Transplant Tissue and Eye Services could open up a pathway to obtain fully ethically consented, human normal and diseased lung tissue to the UK scientific community thereby reducing the need for animal tissue in research. This collaboration will investigate lung tissue but it could be expanded to include almost every tissue/organ type in the body.Invaluable information has been discovered leading to therapies for human disease through the study of human tissues and an infinite amount of time, effort and money saved on unsuccessful clinical trials where observations have not translated from animal tissue. However, obtaining intact human lung tissue for research is currently virtually impossible in the UK. NHS Blood and Transplant, Tissue and Eye Services (TES) are in the unique position of having access to ethically consented human tissue for transplantation and research. TES can retrieve tissue up to 48 hours after death for clinical purposes and currently obtains tissue from 400 deceased donors per year. In addition, TES has the capability to consent for research-only donors, including those with specific diseases. In this way, TES may be in a position to offer normal and diseased tissue to the scientific community. We aim to investigate the viability of lung tissues from this resource across 8 research groups and 3 universities utilising a range of standard bioassay systems at periods of time after lung retrieval. We will provide information regarding the regulatory barriers, how to access this resource, data regarding the viability of primary cells/tissues and all this will be made available to the scientific community as a guide.

Technical Summary

Research is required to identify effective and safe therapeutics for the treatment of lung diseases such as asthma and chronic obstructive pulmonary disease. Much of the research effort currently is carried out in animal models. However, because diseases such as asthma are a uniquely human condition it is sometimes difficult to interpret data generated in animal models and apply the knowledge gained in a logical way to the human disease process. A recent survey identified a need to use fresh human tissue samples for lung research. The major obstacle to obtaining tissues of this sort appears to be the lack of infrastructure and process for distributing the human tissue were consent has been given for donor tissue to be used for research. Currently a significant amount of human tissue is being disposed of in hospitals all over the country. A strategic collaboration between academics and the National Health Service Blood and Transplant Tissue and Eye Services could open up a pathway to obtain fully ethically consented, human normal and diseased lung tissue to the UK scientific community thereby reducing the need for animal tissue in research. NHS Blood and Transplant, Tissue and Eye Services (TES) are in the unique position of having access to ethically consented human tissue for transplantation and research. TES can retrieve tissue up to 48 hours after death for clinical purposes and currently obtains tissue from 400 deceased donors per year. In addition, TES has the capability to consent for research-only donors. In this way, TES may be in a position to offer normal and diseased tissue to the scientific community. We aim to investigate the viability of lung tissues from this resource across 8 research groups and 3 universities utilising a range of standard bioassay systems at periods of time after lung retrieval. We will provide information regarding the regulatory barriers, how to access this resource and data regarding the viability of the tissue.

Planned Impact

The proposed strategic collaboration between academics and NHS Blood and Transplant Tissue and Eye Services (NHSBT TES) could open up a pathway to obtain fully ethically consented, viable, human normal and diseased lung tissue to the UK scientific community thereby reducing the need for animal tissue in research. The main objective is to obtain funding to; (1) set up an infrastructure that will supply human lung tissue retrieved from deceased donors; (2) determine the acceptable preservation methods and timeframe for receipt of tissue that does not compromise research and; (3) to disseminate information which will enable other researchers to access this resource. The academic impact of this project would be significant enabling researchers to validate findings in animal tissue in human samples to allow translation and to put research findings in the context of human disease. Outside of the academic sector tissue would also be available to the commercial sector. Pharma companies make a great contribution to the UK economy, higher than most other high-tech industries. This sector's relative importance becomes even more obvious when considering productivity, measured as Gross Value Added. The pharmaceutical industry adds more economic value than any other sector with each employee contributing more to the national economy than comparable manufacturing sectors. Currently it is virtually impossible to obtain organs from deceased donors in the UK. This severely impacts on the range of techniques and translational work that can be performed and the ability to predict clinical efficacy. Hence it is even more difficult for pharma companies to make informed choices as to which projects to progress limiting the chances of success in the drug development process limiting Pharma productivity. Furthermore, the barriers to drug discovery will extend into and affect patient benefit and thereby raise NHS costs with increased hospital stays and time off work. Currently whole human lung tissue is only available in limited supply from organisations such as IIAM outside the UK. The purchase of tissue for research purposes is often very expensive and utilises UK research funding. In the long term we aim to make maximal use of UK resources in order to use limited research funding to invest back into the NHS rather than contributing to supporting infrastructure in other countries. During the 36 months of this award we aim to establish the infrastructure for the supply of viable human lung tissue to the UK research community and establish guidelines for its use. In the longer term (the following 12 months) this will be made available to the UK research community under the full cost recovery structure described. In the 3-5 years following the award NHSBT TES aim to have a system in place for supply of almost every tissue/organ type in the body to the research community within an acceptable time frame that does not compromise biomedical research.

Publications

10 25 50