The Department of Cell Biology conducts research in the following areas: direct cell-cell interactions in regulating cancer cell migration activity; involvement of connexins, gap junctions and cell adhesion molecules in tumour progression; mechanisms of electrotaxis; mechanisms of lipofection; mechanisms of epithelial–mesenchymal transition (EMT); cancer stem cells, metabolic reprogramming and multi-drug resistance; fibroblast-myofibroblast transition (FMT) and its role in respiratory tract remodelling during bronchial asthma; in vitro skin cell cultures in regenerative medicine: wound treatment and plastic surgery; and the application of stem cells and their derivatives (extracellular vesicles, EVs) in tissue regeneration.
mentioned above is being verified. Another part of our research is concerned with electrotaxis of cells presenting varied strategies of migration (mesenchymal and amoeboid/blebbing).
Lipofection (cationic lipids-based DNA/RNA delivery) is a widely used technique, as well as one of the most promising strategies for non-viral gene therapy and DNA vaccine delivery. However, its main drawback is the lack of efficient and safe lipofecting formulations. Recently, we have developed an innovative lipofection system utilizing cationic polyprenyl derivatives – trimethylpolyprenylammonium iodides (PTAIs). Since some basic mechanisms underlying efficient lipofection remain unknown, we are also investigating cellular uptake mechanisms of polyprenyl-based vehicles. We conduct our research in cooperation with the Institute of Biochemistry and Biophysics, Warsaw, Poland and the Institute of Organic Chemistry of the Polish Academy of Sciences in Warsaw.
Pluripotent stem cells (PSCs), which are characterized by an unlimited ability to self-renew and extensive differentiation potential, constitute an excellent tool in both, basic science and regenerative medicine.These cells rapidly respond to exogenous factors present in their environment, either by differentiation, or apoptosis. Through our studies, we try to understand the mechanisms that regulate PSCs fate decisions. In particular, we are investigating the impact of oxygen concentration and temperature, on genetic stability and biological properties of PSCs and their derivatives. We utilize fluorescence-based reporters and the CRISPR/Cas9 system, as well as in vivo models, to design novel therapies for monogenic diseases (cystic fibrosis) and to alleviate tissue fibrosis, which affects millions of people globally.
Tumour microevolution implies processes that facilitate cells' adaptation to chemotherapeutic stress and their further expansion. In particular, it increases metabolic flexibility of tumour cells and enhances their drug resistance. In our hands, tumours cells adapt to chemotherapeutic stress-induced energy consumption with the reprogramming towards energetically effective aerobic respiration. This increases their vulnerability to metabolic blockers, such as fenofibrate and metformin. Along with the enhancing effects of fenofibrate on the endothelial barrier function during diapedesis, our data suggest their application in the treatment of drug-resistant tumours.
However, tumour cells can adapt to the chemotherapeutic/metabolic stress by generating CD44+ stem cells.
The ongoing research on this topic is focused on:
- the mechanisms underlying metabolic adaptation of tumour cells to chemotherapy and to metabolic blockers;
- consequences of metabolic reprogramming for the invasion of tumour cells and diapedesis;
- the role of connexin(Cx)43, stromal and stem cells in these processes and
- dietary compounds interfering with the metabolic adaptation and drug resistance of tumour cells.
Our GMP laboratory specializes in the manufacture of skin tissue-engineered products used for extensive burn treatment in the clinic. Additionally, we prepare mesenchymal cells products in combination with extracellular equivalents for connective tissue regeneration and chondrocytes for chondromalacia treatment. We are constantly working on the improvement of wound healing strategies using skin cells and acellular matrices, conducting basic research in this area. The long-term experience of the Cell Bank in development of ATMPs allow us to offer a service to implement the new results of research in the field of ATMPs for clinical application. In addition to clinical research, we are working on a new source of epidermal stem cells to obtain a complete regeneration of the skin together with its appendages. Furthermore, we use in vitro-cultured epidermal cells as a model to study mechanisms related to the pathology of psoriasis and atopic dermatitis.
The research focusses on the role of myofibroblasts in the fibrotic lung tissue. Studies primarily discuss: 1. The nature of phenotypic fibroblast-to-myofibroblast transition (FMT) and its underlying mechanisms during bronchial airway wall remodelling in asthma. 2. Differences between asthmatic and non-asthmatic bronchial fibroblasts (HBFs) in response to the transforming growth factor β (the main profibrotic cytokine). 3. Mechanisms of the enhanced asthma-related epithelial–mesenchymal transition. 4. Functional interactions between human bronchial epithelial cells (HBECs) and HBFs within the epithelial-mesenchymal trophic unit. 5. The effects of some selected compounds (e.g. flavonoids, statins, chalcones, PPAR agonists) on FMT efficiency in HBFs.
The research of our group is focused on studying a role and mechanisms of action of selected adult and pluripotent stem cells (SCs) in tissue repair, including cardiovascular and bone regeneration. Our recent projects conducted in international cooperation are also focused on exploring bioactive properties of SC-derived extracellular vesicles (EVs), examined in several cellular in vitro- and animal in vivo-models. Another interdisciplinary branch of the research is dedicated to combining SCs with biomaterial scaffolds for effective tissue repair and translational aspects to develop novel therapeutic approaches in humans, an area in which we are very actively engaged in collaborating with clinical centres and conducting clinical trials.
Pancreatitis is a serious disease in which the tissues becomes destroyed by prematurely activated digestive enzymes stored in acinar cells, often leading to permanent tissue scarring – fibrosis. Pancreatic fibrosis remains very poorly studied, possibly because the main cellular mediators – pancreatic stellate cells – have long been overlooked. In our research, we apply real-time imaging techniques 2+ to investigate signalling events (Ca or ROS signals) induced by pathophysiological stimuli in pancreatic acinar or stellate cells; and we aim to understand the implications these signals have for the development of pancreatitis and pancreatic cancer. We also use animal models of pancreatic diseases to test new therapeutic strategies based on selective regulation of cell death in pancreatic cells.