Recent years of studies devoted to the creation of an infallible biological prosthesis of the heart valve belong to tissue engineering. Scientists unanimously claim that restoration of the life of the valve will secure its functionality for a longer period. Within the scheme of the project entitled ‘New methods of preparing biological valves’ a prototype of an autological valve is being developed, i.e. a biological heart valve obtained via the method of tissue engineering, in which an acellular or biodegradable scaffold of the prosthesis will be covered with the patient’s own cells (isolated from the bone marrow).Such a valve would be free from the complications likely to occur when contemporary valve prostheses are used (frequent calcification, inflammatory reactions, patients’ higher susceptibility to infections, the necessity of administering anticoagulants, low durability, etc.).
The project assumes using human tissues as a material for the valve. Nevertheless, limitations relating to the availability of human material incline to work simultaneously on the development of a method of creating valve bioprostheses based on zoonotic (xenogenic) material, subjected to chemical preservation with compounds which are non-toxic for living cells. It will allow to create advanced heart valve prostheses, which thanks to the possibility of the alternative use of zoonotic tissues will be able to be broadly applied.
During the project implementation a number of tests were performed so as to evaluate biological properties of the valves. Histological tests allowed to assess to what extent modification of tissues, relating – without limitations – to the enzymatic method of cell removal, may have its effect on their structure. Biomechanical and haemodynamic tests aimed to determine whether and to what extent the tissue fulfils its mechanical function after modification. A crucial role was also fulfilled by studies the goal of which was to determine the conditions of growing cells after their isolation, and the parameters allowing to differentiate cells isolated from the bone marrow, as well as to determine e.g. their functional features. A system of a bioreactor was developed, allowing to grow cells in dynamic conditions with a set flow, along with a number of new methods of chemical preservation of tissues, with the application of chemical compounds (e.g. from the group of the so-called flavonoids) which do not exhibit cytotoxicity. Promising research results will constitute the foundation for formulating an application to the bioethics committee for a permission to conduct tests on animals. All effects reached within the scheme of the project are subject of relevant patent applications.
Implementation of the project led to cooperation with the University in Leipzig (Prof. A. Bader), with the academic centre in Gdańsk (Piotr Siondalski, Ph.D. M.D.), and with the Ship Design and Research Centre in Gdańsk (Leszek Wilszyński, Ph.D).
The constant disproportion between the number of donors and that of potential recipients constitutes a crucial limitation affecting the use of human tissues as a material for creating heart valve prostheses. For this reason zoonotic tissues seem to be an alternative in this respect. In this case, liquidation of cells by means of enzymatic and chemical methods in such tissues causes the removal of most of them, although it also poses a risk that some cells or their parts will remain, constituting a source of antigens. Therefore, in valve prostheses the aim is to use zoonotic tissue deprived of reactive antigens, as it would stimulate an immunological reaction of the human body much less, which in turn would translate into the increase of the durability of the bioprostheses applied. In this respect, breeding transgenic animals for the purposes of tissue engineering gains special significance and justification. Since the problem of degradation and loss of functions of valve bioprostheses is particularly intense in children and young patients, it seems that this group of recipients could benefit the most from the proposed solutions.
The goal of the project is to develop methods of isolation and differentiation of stem cells which could be used in the regeneration of a damaged cardiac muscle, in procedures enhancing the systolic function of the heart. The project is implemented in the consortium with the Silesian Centre for Heart Diseases in Zabrze and the Cancer Centre in Gliwice. Cardiac stem cells are located in the cardiac muscle. Probably, unlike other stem cells, they pose a lower risk of neoplasms or risk of differentiating into another, undesirable type of cells. Therefore, the chance that they will form cells of the cardiac muscle, new blood vessels, and not e.g. renal cells, is better.
In 2010 the group of sponsors of our Foundation obtained yet another member, the Upper Silesian Gas Distribution Company (Górnośląska Spółka Gazownictwa, Sp. z o.o.) in Zabrze. The company authorities decided to support our research on a new generation of heart valve prostheses. The valve is to be applied in the treatment of congenital and acquired heart diseases in children and adults. Thanks to the funds allocated to this purpose, the Foundation’s research facilities were enriched with two unique devices facilitating the works conducted. In 2011 in the Bioengineering Laboratory of our Foundation Poland’s first apparatus for automatic modification of heart valve prostheses was constructed. The device allowed to control the application of polyelectrolytes facilitating the process of seeding cells on heart valve prostheses. Its use opened up another stage of in vitro tests devoted to the development of a new generation of hearth prostheses.
In 2012, on the other hand, a device was designed which much facilitates and automates the process of cell seeding and culture on heart valve prostheses. The presentation of the device was attended by representatives of the Sponsor and the authorities of the Foundation.
|XII Dzień Nauki w Zabrzu.|
Piotr Wilczek PH.D.Sc., Professor of HPI
Chief of Bioengineering Laboratory
+48 032 37 35 675
fax: +48 032 37 35 677
Aleksandra Niemiec-Cyganek - Deputy Director
Anna Barańska- Lesiak