Projects / Programmes
Designer cells for wound healing and neuroregeneration
| Code |
Science |
Field |
Subfield |
| 3.03.00 |
Medical sciences |
Neurobiology |
|
| Code |
Science |
Field |
| B000 |
Biomedical sciences |
|
| Code |
Science |
Field |
| 3.01 |
Medical and Health Sciences |
Basic medicine |
cell therapy, wound healing, trophic factors, neuroregeneration, neurodegeneration, Alzheimer's disease, encapsulation, regenerative medicine, diabetic wound
Researchers (11)
Organisations (2)
Abstract
Background and problem identification. Stem cell therapy is one of the most promising approaches to regenerative medicine problems such as chronic wounds and neurodegeneration. Several recent studies demonstrated that stem cell therapeutic properties to a large degree rely on soluble factors, secreted by stem cells. In this respect stem cells act as in situ production and local delivery vehicles of trophic factors as biological drugs. There are however, several problems associated with stem cells, such as low yield and high cost of isolation, potential for the development of cancer, uncontrollable spread and behavior upon introduction into the body, which poses safety and efficacy questions. Secretomes of stem cells contain a variety of growth factors and other bioactive molecules. Current therapeutic settings using trophic factors rely predominantly on a single soluble factor, while we propose that effective treatment should make use of the synergistic effect of several different soluble factors mimicking the properties of stem cell therapy.
The idea and objectives of the study. We propose to prepare a therapeutic device for the regenerative medicine by engineering mammalian cells to stably secrete a single trophic factor, combine the selected combinations of trophic factor producer cells according to the principle “plug-and-play” at the appropriate ratios for each therapeutic application and to introduce the therapeutic cells confined within the sealed semi-permeable container into the affected tissue. In contrast to stem cell therapy at the termination of the therapy the container with cells could safely be removed.
Our work will be focused to achieve three major objectives:
1. Establishment and validation of the collection of stable cell lines secreting trophic factors required for the regeneration
We will prepare and validate the collection of stable cell lines each secreting a single trophic factor. The selected carrier cell line will be hardy (to survive harsh conditions of the wounds and inflammation), non-tumorigenic and will contain a safety kill-switch.
2. Construction and validation of the therapeutic designer cell device for wound healing
The proof-of-principle of this type of therapy will be demonstrated all the way from the determination of the optimal combinations of trophic factors in cell culture and organotypic culture models of wound healing to the functional animal studies that should provide the information on the therapeutic efficiency.
3. Selection of optimal trophic factor combinations for the therapy of Alzheimer’s disease
Combinations of trophic factors will be screened on neuronal cultures and later on organotypic brain slices of animal model of Alzheimer’s disease. The objective of this work package is to establish an optimized combination of neurotrophic factors to fight neurodegeneration in Alzheimer’s disease.
Originality, relevance and potential impact of the study. Project proposal connects stem cell research and synthetic biology as the two among the fastest evolving scientific fields in life sciences in order to provide the foundation for the designer cell-based therapeutics. In the project we will specifically address two widespread but devastating medical problems, chronic wounds and Alzheimer’s disease, however, our approach and the therapeutic cell collection could be customized for treatment of many other diseases or injuries. The fact that engineered cells can also produce designed therapeutic proteins such as neutralizing antibodies provides additional advantage of our approach over stem cells and even broadens its applicability.
Significance for science
Over the past decade there was an enormous effort put into elucidating the effectiveness of stem cell therapy and of trophic factors for wound healing and also for the treatment of neurodegeneration. While stem cell therapy is problematic in safety and economic aspects, single trophic factor treatment did not provide desirable results. During the project we investigated the effects of various combinations of biologically active compounds on various models of regeneration (wound healing, bone regeneration, muscle innervation). In addition to growth factors, we also included antimicrobial and antiinflammatory proteins. Inflammation is one of the key processes, being investigated in our lab on the molecular basis. Combined knowledge on effective trophic factor combination, novel findings in the molecular mechanisms of the disease and synthetic biology tools could lead to the development of the next generation designer cell devices, which are able to respond to endogenous signal with release of appropriate trophic factor. Our interdisciplinary approach combining the expertise from synthetic and cell biology, immunology to neuroscience represents innovative and original contribution in these very competitive disciplines and might open new therapeutic possibilities in a variety of common diseases. The knowledge gained during this project was the basis for the upcoming EU project application.The members of the research group passed their knowledge to scientific community through international workshops and conferences and publication of scientific papers in peer-reviewed journals.
Significance for the country
Chronic wounds represent high economic burdens for developed countries and with aging population and the increase in obesity and diabetes the numbers are only increasing. During the project we developed designer cell devices for treatment of chronic wounds and bone regeneration. We applied for IP protection (filed a patent application to international patent office), which was the basis for presentation of our results to industry and potential investors (in case that further development of the technology would be based on spin-off company). The members of research group are frequently providing their know-how to Slovenian as well as foreign industry. The interdisciplinary nature of the project opens new possibilities for international cooperation with researchers with whom we already collaborated e.g. within European projects and bilateral projects and with new collaborators. Within this project we also collaborated with several groups from Medical Faculty University of Ljubljana and Jožef Stefan Institute. On the topic of this project one PhD student will defend her thesis in 2019 and one masters student in 2018. The members of the research group are frequently communicating science to lay community through journal articles, radio interviews and participation on television shows. The PI was also coordinator of consortium project, which promotes science to high school students. In 2014 we organized a summer camp ‘Evidence-based medicine’, where we also presented some of the work on trophic factors. Members of the project group also participate in promoting Slovenia, especially through mentoring student groups, which earned great successes in international competitions iGEM and Biomod.
Most important scientific results
Annual report
2014,
2015,
final report
Most important socioeconomically and culturally relevant results
Annual report
2014,
2015,
final report
