Projects / Programmes
Human stem cells-advanced cell therapy II
January 1, 2013
- December 31, 2016
| Code |
Science |
Field |
Subfield |
| 3.04.00 |
Medical sciences |
Oncology |
|
| 3.01.00 |
Medical sciences |
Microbiology and immunology |
|
| Code |
Science |
Field |
| B490 |
Biomedical sciences |
Haematology, extracellular fluids |
| Code |
Science |
Field |
| 3.02 |
Medical and Health Sciences |
Clinical medicine |
| 3.01 |
Medical and Health Sciences |
Basic medicine |
Researchers (18)
Organisations (3)
Abstract
Our research programme introduced advanced therapies to Slovenia. The basis of all three forms of advanced therapies - i.e. cell therapy, tissue engineering and gene therapy - are the human stem cells. In the current national research programme we successfully combined and coordinated stem cell (SC) research from various Slovenian institutions and laboratories.
Under the current research programme we developed protocols for collection of SCs from cord and peripheral blood and bone marrow, cell separation and cell sorting on selected surface markers, isolation of specific subpopulations of SCs and their long-term cryopreservation. We developed protocols for differentiation of SC into all three germ layers, protocols for various molecular methods used to determine gene expression and culture conditions that enable ex vivo expansion of SCs. We also acquired extensive knowledge from the transcriptomics and metabolomics of SCs. The new knowledge was used in clinics where these methods were successfully used to treat hundreds of patients in University Clinical Centre, Ljubljana.
Although the cell therapies were successful, we would like to achieve a substantial improvement in the quality and success of this treatment in the future. Therefore we need to optimize procedures for isolation of SCs from peripheral blood, bone marrow, umbilical cord, adipose tissue and other adult tissues on the preclinical level. Isolated cell populations need to be appropriately characterized on the molecular, phenotypic and functional level. Clonal lines need to be isolated and protocols for directed ex vivo expansion developed. Various growth factors, especially ones derived from activated platelets preparations will be used. Our goal is to manufacture standardized stem cell products and to thoroughly determine their cell composition – we are especially interested in adult stem cells with broad differentiation potential described in various tissues and organs (VSEL – ESC-A). We plan to optimize the collection of autologous HSC from patient’s mobilized peripheral blood by apheresis (UKC, Department for Haematology). With improved cell preparations, we will carry out controlled clinical studies, such as treatment of long bone fractures and the treatment of chronic wounds (UKC, Department for Surgical Infections), heart failure (UKC, Department of Cardiology), patients with damaged articular cartilage will be treated with implantation of autologous cells (UKC, Orthopaedics Clinic), and treatment of advanced alcoholic liver cirrhosis (UKC, Department of Gastroenterology).
The final aim of this research programme “HUMAN STEM CELL – ADVANCED CELL THERAPIES II” remains the same: to provide a quality medical service in the field of advanced cell therapies to all citizens. It will open the possibilities for a replacement of damaged and diseased tissues and thus high life quality. By introducing new essential technologies, the proposed programme is also important from a scientific, technical, infrastructural and educational viewpoint.
Significance for science
Advanced cell therapies are one of the main developmental directions of biomedical research in the last decade. The new post-genomic technologies and system biology have answered many basic scientific questions. We predict that the impact of advanced therapies in medicine in the coming years will grow rapidly. The central scientific question of our endeavours was why has been the benefit of cell therapies lesser then expected. Our hypothesis was that the major problem represented the use of non-optimal cell preparations and incomplete clinical protocols. We also believe that the grafts should contain a bigger population of SCs with a broader developmental potential. The investigations were divided in two groups. The findings from the first part (preclinical part) of our research programme and the development of successful in vitro procedures for isolation and enrichment of stem cells with broad differentiation potential enable the production of better cellular products. New knowledge also increased our understanding of the SC development, which is an important step in the development of advanced cell therapies. Our improved processes enable the production and use of better therapeutic cell products, while increasing the understanding of the biology of the stem cells and the mechanisms of their use in regenerative medicine. Soon we will also answer some specific questions, such as which subpopulations of stem cells are to be used in certain transplant settings, and what should be their optimal composition. Findings from the second part (clinical research) are the basis for wider clinical use of different types of stem cells and other cells. They offer the answers to the question whether and to what extent are the cell therapies superior to the established traditional medical treatments. These findings are enabling further extension of the clinical indications in degenerative diseases and injuries of the nervous system, diabetes, and treatments of various cardiovascular diseases, which have already been launched as a side effect of our scientific efforts. In addition to this we have also paved the way for new field by using models of bone marrow transplantation in experimental animals, which was so far missing in Slovenia and now provides a number of new approaches in regenerative medicine, immunology, as well as in pathology and prevention of aging and its associated degenerative diseases. Our Research Program met the set goals and laid the foundations for further research in the field of experimental hematology. Scientific weight of this Research Program in the form of articles, conference reports, citations and its international impact have far exceeded all our expectations, which can be attributed to well organized multidisciplinary research group consisting of 17 members. According to the COBISS.SI, our Research Program group with their coworkers published around 300 bibliographic units and collected around 3,000 total citations in the field of stem cells and regenerative medicine during the period after 2013. Also important is the educational impact of our scientific Program since its contents and the outcomes were introduced into a number of courses and programs in the members of University of Ljubljana (Faculty of Medicine, Biotechnical Faculty and Faculty of Pharmacy). Several educational textbooks were published. Consequently, a large number of bachelor, master, and doctoral degrees were accomplished and several academic titles in the form of Assisting professorship, Associate and Full Professorships were assigned to our members, colleagues and co-authors.
Significance for the country
Direct relevance for the economy and society: The European population is aging rapidly and therefore; it is increasingly in need of regenerative medicine services. Replacement of damaged or diseased tissues greatly contributes to successful treatment and rapid rehabilitation. Only superior and high quality medicine can grant citizens of Slovenia the effective treatments and high quality of life. Our research programme has direct and indirect effects on the patients and society as a whole. The importance for the industry: Advanced therapies have become a new branch of medicine that generates many new jobs in developed countries. Our Research Program largely contributes to the visibility, development and promotion of regenerative medicine and medical biotechnology. We estimate that new jobs will be opened as a consequence of this programme. We expect a rapid development of intellectual property, new international patents and the formation of spin-offs along the lines of company Educell. The importance for social infrastructure: In the last 10 years, we were aware of the new world trends and we managed to create a solid infrastructure, educated personnel and good achievements in the field of regenerative medicine and medical biotechnology. This branch of medicine is extremely propulsive even as an industry, because it is environmentally friendly and allows for continuous development of economy, medical and health tourism, and development of University system of education, and of course, of the general science. Importance for Public Administration, cultural development, and protection of natural and cultural heritage: Our programme promotes an ecologically pure and virtuous activity, based on high technology and knowledge. The programme is an opportunity for international recognition of Slovenia, since it helps to incorporate Slovenia into international relations, it opened the collaborations within the EU's Horizon 2020, it allows the appropriate education of staff for the further development of the medical profession, as well as further development of our field.
Most important scientific results
Annual report
2013,
2014,
2015,
final report
Most important socioeconomically and culturally relevant results
Annual report
2013,
2014,
2015,
final report
