The subject, focus, and goals of the project

A new direction in medicine, the results of which are now bringing it to the fore, consists of methods of modern therapy using living cells, genetic information, and nanotechnology. The proposed project aims to build, as part of the Institute of Experimental Medicine AS CR, v.v.i. (IEM), and innovative research centre for basic research methods of modern therapy including research into the safety and effectiveness of their use. The project is focused on one of the world's fastest growing directions of research, into the medical applications of molecular biology, specifically in cellular approaches and the use of nanomaterials in biomedicine.

Research Centre for Cell Therapy and Tissue Repair (hereafter CTTR or Centre), which was built as part of the project, will focus on basic research of advanced therapy products, the safety of their preparation and use (including environmental) and effectiveness (efficiency), including research on innovative methods of identification, and the mediation of these methods (both information on them and their realization) available to the scientific, medical, and general public. The investor, owner and operator of the project will be the IEM, which will also provide staffing of the project so as to ensure the high quality of excellence of the research, thus leading to stable funding through national and European grants for basic research. The construction of the research centre will lead to targeted basic research and will improve the situation for highly innovative companies and research institutions that develop products for regenerative medicine and cell therapy in Prague. The submitted project synergistically uses infrastructure built in the JPD2 - business incubator for innovative SMEs, companies focused on production in clean rooms. At present, the business incubator is fully occupied and exceeds all monitoring criteria.

The core of the resulting product is to be a set of knowledge of safe and effective therapeutic methods which offer therapy for currently incurable disease and damages or those which shorten and/or reduce the expenses of the healing process in comparison with currently available medical procedures. The successful realization of the project will result in a separate product - infrastructure within IEM that will enable the "production" of the above mentioned product – a research centre focused on medicinal products for modern therapy:

• basic research in cell therapy and tissue repair products,
• basic research in deployment of nanotechnologies in therapeutic procedures,
• basic research in safety, efficiency, and effectiveness of the two aforementioned interdisciplinary fields
   

"Research Centre for Cell Therapy and Tissue Repair" (CTTR).
The centre will provide basic research in all aspects of safety (research of safety and effectiveness of methods of modern therapy, including research on the methods of its identification, environmental safety, communication of research results towards the scientific, medical and general public). The Centre's activity will be mostly funded from the Czech and international (e.g. 7th Framework Programme) grants for basic research. During the first two years of the research centre's operation, the concept and practical realization and security policy of applications of stem cells and nanotechnology in biomedicine will be created. A portfolio of three to five bearing directions from which at least one will be passed over to the stage of applied research in the Innovative Biomedical Centre.

The research program of the Centre in the first years will be focused on the following topics:

• Efficiency (differentiation, gene expression), and safety of undifferentiated mesenchymal stem cells isolated from bone marrow and adipose tissue and those used for treating diseases of the blood vessels and connective tissues (bone, cartilage, tendon, skin, muscle).
• The safety of the application of stem cells (mesenchymal, but also embryonic and fetal cells from the currently existing cell lines) into nerve tissue, for the treatment of ischemia, demyelinating disease, and spinal cord injury.
• Environmental toxicology of cells used for therapy and therapeutic nanoparticles used.
• Safety of use of cell therapy and tissue repair in marginal age groups, differences in the effect of therapy in senescence.
• Differentiation of stem cells by the effect of growth factors and safety of application of in vitro differentiated cells.
• Innovative laboratory methods of determining the properties of products containing nanotechnology (nanoparticles, nanofibers), from the level of protein engineering to cell interactions.
• Ontology (explicit specification of conceptualization) of the potential serious side effects of products for advanced therapies and the development of knowledge-based methods for classification and description of these side effects.
• Research of biomaterial characteristics used to construct tissue repair using tissue engineering.

The operational phase is planned for the period from 1.1.2013 to 31.12.2022, i.e. for 10 years. This time period was determined based on an expert estimate of the life span of most instrumentation and other CTTR laboratory equipment due to physical and moral wear. The CTTR team will be integrated into the IEM as a separate "CTTR Department" with established department heads who will assume responsibility as project manager for the operational phase (compliance with the terms of the grant and preparation of monitoring reports). From the viewpoint of human resources, the creation of at least 5 new jobs is expected, 3 of which will consist of highly qualified researchers and 2 will be occupied by prospective scientists in positions of junior researcher or PhD student. Other current employees of the applicant will participate in the results of CTTR research programs, headed by expert guarantors forming "Board of Experts of the project" (Prof. Sykova, Ass. Prof. Chvatal, Dr. Jendelova).  The financing of the operational phase will take place based on the applicant's institutional funds (about 40%) as well as received research grants related to the project (more than 60% expected). These funds will be used for the incurred operating costs.

Expected scientific outputs and its form at the end of the reporting period:

1. Mastery of technologies of targeted differentiation of stem cells - methodology
2. Description of cellular and molecular mechanism of the immune response to transplanted stem cells – predictive model
3. Functionalized nanofibers and microcapsules - specific samples
4. Effective materials for the transport of bioactive compounds - specific samples
5. Effective biomaterials for tissue regeneration - specific samples
6. Facilitatory biophysical methods - methodology

With the financial autonomy of the Centre we can not count, but granted support the Centre will have a significant benefit in that the structure of the funding transferred away from insecure institutional to joint projects funded from grant funds.

These were the basis for the formation of the project of the Research Centre for Cell Therapy and Tissue Repair, technological equipment and its concept of cooperation of three professional specializations, namely:

- Department of Tissue Engineering (led by Prof. Amler)
- Department of Transplantation Immunology (led by Prof. Holan)
- Laboratory of Biomaterials and biophysical methods (led by Dr. Kubinova)
within the Department of Neuroscience led by prof. Syková.