CriTiClean · Supercritical carbon dioxide for delipidation of soft tissue - Suppressing transplant rejection.
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2017-05-22 → 2019-07-13
- EU contribution
- €173,857
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
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Results in brief
Supercritical carbon dioxide for delipidation of soft tissue - Suppressing transplant rejection.
The lack of donor organs and tissue constitutes a health and social problem. Even though the global rate of transplantation increased by 7.25% between 2015 and 2016, less than 10% of the transplant needs are covered, which results in a high unbalanced supply-and-demand rate. A failed transplantation process is mainly due to the presence of cellular components in the donor tissue. Biological extracellular matrix (ECM) technology, aims to obtain functional scaffolds from animal sources, where cellular components are removed while keeping the mechanical and architectonic characteristics of the ECM. Mentioned cellular components to be removed are lipids and genetic material. Lipids residues may hamper ECM production as certain lipids impairs recellularization by poor cell attachment and they may act as a source of pro-inflammatory fatty acids. Moreover, residual antigens (dsDNA) should be minimized to avoid the activation of the host immune system. Traditional decellularization methods are based on surfactant-enzyme treatments. Such processes are high time consuming and were proven to damage the ECM by fibre’s break and/or crosslinking. Moreover, detergent leftovers may present toxic effects in the host. Therefore, there is a need of new alternatives to produce suitable ECM scaffolds which avoid the use of detergents while ensuring a safer transplantation process. CriTiClean was conceived to offer new alternatives to the worldwide transplantation issue. This project focused in the exploration of pressurize CO2-based fluids to remove lipids and, if possible, other cellular components from donor tissues. CriTiClean approach avoids the use of chemicals, avoiding the side effects of traditional processes. This newcoined biomedical application of pressurized CO2-based technology gained the attention of the scientific community in the last 10 years. Therefore, very scarce information related to the effect of such technology on the tissue lipid composition after treatment can be found in the literature. CriTiClean action plan was based on an exhaustive delipidation study from an analytical chemistry point of view, while keeping the interest in dsDNA removal and preservation of ECM integrity. At the term of CriTiClean, the hypothesis set in the action was confirmed, with few restrictions: certain pressurized CO2-based fluids are able to remove lipids and other cellular components (after enzyme treatment) from porcine soft tissues, without jeopardizing the structure and architecture characteristics of the native tissue. However, the presence of immune reactive components (dsDNA) is still an ongoing issue. In conclusion, CriTiClean outcomes proved that this new decellularization approach deserves to be continued in future projects.
Data: CORDIS, © European Union
Project objective
The lack of donor organs and tissue constitutes a health and social problem. In 2014 about 119.873 organs were transplanted, that is less than the 10% of global needs. Critical patients do not survive the waiting time while transplanted people must receive lifelong immunosuppressive therapy with severe side effects. Also, there is a risk to lose the new organ to chronic rejection, which is linked to the presence of cellular components e.g. glycolipids and lipoproteins in the donor tissue. There is currently no process to remove lipids and lipid antigens from soft tissue prior transplantation.Supercritical carbon dioxide (scCO2) is known to extract lipids from solid matrices, while polar molecules of high molecular weight, such as structural proteins in soft tissue, are insoluble. In this project we will explore the use of scCO2 to remove lipid compounds from soft tissue (i.e. pulmonary arteries) as a novel process for tissue preparation in order to suppress the main cause of rejection associated with transplantation. Fundamental studies on solubility of lipids in scCO2-water-ethanol mixtures are necessary to evaluate the extractability of lipids from fresh tissue, and will be performed by 'in-situ' Raman spectroscopy. Our approach avoids the use of current chemical and biological treatments that risk damaging the tissue and pose a toxic threat to the recipient organism. The mechanical properties of the “cleaned” tissue, the immunoresponse that provokes and its capacity for recellularization will be studied 'in vitro' and related to the amounts and type of remnant lipid compounds. The project brings supercritical fluid technology into the biomedical field. This work will lead to efficient methodologies to “clean” all kind of organs/soft tissue and will enable safe animal-to-human transplantation, a current dream that will increase the hope of critical patients and improve life-quality after transplantation by removing the need of immunosuppression.
Original text from CORDIS.
Participants
- LUNDS UNIVERSITET · LundCoordinatorSweden
Links
Data: CORDIS, © European Union