Department of regenerative medicine

PhD Eiva Bernotienė

Head of the Department
+370 5 2626049

Demographic change and a rapidly aging population is driving policy-makers and scientists to accelerate their efforts to innovate in healthcare, especially in the area of tissue repair, regeneration and reconstruction and the design of new therapeutic strategies for degenerative, inflammatory or environmental factor-associated diseases of synovial joints, cardiovascular system or lungs.

Relevant technical facilities together with high intellectual potential are concentrated at the Department of Regenerative Medicine of the CIM. The department employs experienced scientists, including molecular biologists, immunologists, physiologists, pathologist, collaborating clinical scientists and medically qualified doctors, who have extensive networks and numerous collaborations worldwide. Our staff participate in joint European, industrial and international projects.

We have high level collaboration with laser physicists, chemists, surgeons, rheumatologists and other professionals, which makes our department an ideal partner for joint multidisciplinary projects and European Commission consortia.

Experiences of investigators

We apply innovative technologies and have extensive expertise in isolating and cultivating primary cells, e.g. human mesenchymal stromal/stem cells (MSCs), other progenitor and differentiated cells, their characterization, expansion, manipulation and implementation of innovative regenerative technologies.

We have developed detailed protocols and standard operating procedures for the isolation and characterization of MSCs and other cells from a variety of human tissues, including bone marrow, articular cartilage, adipose tissue, cardiac muscle, skeletal muscle, menstrual blood and synovial fluid. We have extensive knowledge and experience of a wide range of morphological and functional assays for the characterisation of adult MSCs and progenitors and differentiated cells, as well as induced pluripotent stem cells.

Our current research is done to understand the biological properties of these cells and their potential for clinical applications, including possible mechanisms of action, safety and targeted regeneration. We have the capacity for establishing ex-vivo models of human cartilage, synovial tissue and cultures of isolated chondrons. We employ electric and mechanical stimulation and the analysis of mechanotransduction pathways well is within range of our capacity and scientific expertise.

Current research topics focus on degenerative and inflammatory diseases and cellular therapies with particular emphasis on regenerative medicine for articular cartilage, cardiac and lung tissues.

Fields of the investigation

Principal research topics at the Department of Regenerative Medicine include: studies on the capabilities of cellular therapies for osteoarthritis and cartilage defects, heart and skeletal muscle, chronic obstructive pulmonary disease (COPD) and other degenerative lung diseases, arrhythmias, autoimmune, inflammatory and other diseases; mesenchymal stem cell -based therapies and their cultures in 3D scaffolds for engineering of cartilage, lung, muscle and cardiac tissues, pacemaking technologies; investigation and characterization of aggressive cells in rheumatoid synovium and progenitor cells in cartilage; mechanotransduction and calcium signaling in cartilage and cardiac cells, effects of calcium channel inhibitors, epigenetic changes, including methyl, acetyl and other groups, modifying agents and their effect to the cells; application of photodynamic therapy, nanomedicine and others.

The search of disease biomarkers for osteoarthritis and development of multiplexed immunodetection nanobiosensor are the important fields of our interests at the department. We also work in the area of respiratory health assessing mechanisms of injury, i.e. cigarette smoking, air pollution etc., designing novel models and markers for in vitro studies and investigating novel candidate therapies.

Capital Equipment and Research Infrastructure

The department is well-equipped with cell culture facilities, including two CO2 incubators (O2 controlled), mechanical compression system (Flexcell FX-5000), electric stimulation system, flow cytometer/sorter (FACS Aria), fluorescent and light microscopes, scanning fluorescent fully automated, high-resolution EVOS M7000 Imaging System, functional histology and immunohistochemistry lab, equipment for PCR, RTq-PCR, western blotting, 2D electrophoresis, cell electroporation, multiplex detection system (Luminex), plate-reader “Spectramax” for measurement of absorbance, fluorescence and luminescence, magnetic particle-based cell sorter (MACS), ultra-low temperature freezer (-150˚C), etc.

Models

Cells and Tissues
  • Primary tissue-derived explant cultures of cartilage, meniscus and synovium.
  • 2-D and 3-D culture of primary chondrocytes and chondrons from cartilage.
  • 2-D and 3-D culture of primary human cardiac and skeletal muscle-derived cells.
  • 2-D and 3-D culture of primary bone marrow, synovial, adipose tissue, placental, dental pulp, umbilical and menstrual blood-derived cells.
  • In vitro models of chondrogenic, cardiogenic, myogenic, epithelial, osteogenic tissue differentiation in various artificial niches and tissue-specific environments, i.e. scaffolds, hydrogels, spheroids and high-density systems.
  • Modelling of mechanical load effects on 3-D chondrocyte or cardiac cell cultures, cartilage or cardiac tissue explants, using the Flexcell system.
  • Development of ‘Organ-on-Chip’ models of lung tissue using established lung-derived cell-lines, scaffolds and decellularized lung explants.
Animals
  • Animal models of osteoarthritis, inflammatory arthritis, wound healing, subcutaneous implants of engineered tissue in vivo, exposure of laboratory animals to pollution
Devices
  • Experimental development and pre-clinical implementation of 2D and 3D devices suitable for the investigations of cartilage, skeletal, cardiac, pulmonary and other types of biomodels in vitro and in vivo.
Equipment
  • Quantitative RT-PCR.
  • Transfection models for gene expression and silencing.
  • Proteomic analysis of cells, tissues and secretomes using western blotting, ELISA, Spectramax and Luminex-based platforms, etc.
  • Microscopic imaging using light, fluorescent, confocal microscopes, quantitative analysis of fluorescence using EVOS M7000 Imaging System.
  • Analysis of cell surface/cytoplasmic markers and cell sorting with the FACS Aria II/magnetic activated cell sorting (MACS).
  • Multiplexed biomarker detection from blood, plasma, serum, culture medium with Luminex 200 system.
  • Platforms for mechanical and electric stimulation of cells.
  • Equipment for histological and immunohistochemical analysis of samples.

Main recently implemented projects at Department of Regenerative Medicine:

  • International Framework Programme FP7, Large Scale Collaborative Project “Adipose Derived Stromal Cells for Osteoarthritis Treatment” Acronym ADIPOA. Leader of IMC partner Dr. E. Bernotiene
  • Global Dotation “Native matrix-based in vitro model of alveolar lung tissue: implications of mesenchymal stem cells in emphysema repair” Leader Dr. Ruta Aldonyte.
  • ESFA project „Development of Biological cardiac pacemaker” BIOCARDIOSTIM; Leader of IMC partner Dr. E.Bernotiene.

 

Main current projects at Department of Regenerative Medicine

  • High-level R&D project: “L-type calcium channels as potential therapeutic targets for osteoarthritic cartilage metabolic processes” (Project number: DOTSUT-215), 2018-2021. Project Leader:  Prof. A. Mobasheri;
  • Project funded by Research Council of Lithuania: Analysis of The Regenerative Potential and Mechanoptosis of Primary Cardiospheres of Human Heart Muscle; 2017-2020. Project Leader: Dr. D. Bironaite
  • Joint Lithuanian–Latvian–Chinese (Taiwanese) Tripartite Cooperation Programme in the Fields of Science and Technologies: “Creating a new type of injectable biomimetic hydrogel for cartilage tissue engineering” (Project Contract Number: S-LLT-18-4); 2018-2020; Project Leader:  Dr. E. Bernotiene
  • SMART projects (Targeted Research in Smart Specialisation Areas (Funding instrument – European Regional Development Fund): measure implementation is managed by the Ministry of Education, Science and Sport of the Republic of Lithuania and the Research Council of Lithuania. The purpose of the measure is to implement research projects intended to develop results compliant with R&D relevant for economic sectors and that could subsequently be commercialised):
  1. High-level R&D SMART project: Development of a nanobiosensor: a multiplex analysis of diagnostic biomarkers for personalization of arthritis therapy (Agreement No. DOTSUT-1 (01.2.2-LMT-K-718-02-0022), 2019-2022; Project Leader: A. Mobasheri; principal member of the research at host Institution IMC Dr. E. Bernotienė; Budget: € 996 215
  2. Individualised nasal microbiome test – novel tool for diagnostics and health care (YourAirwayMicrobiome); 2020-2023 Budget: € 529 766; coordinated by IMC, Project Leader Dr. R. Aldonyte.
  3. Cellular nanofiber matrix-based biosensors – integrated platform for the cytotoxicity assays of air pollution (AerocellTox) – 2020-2023, Budget: € 698030; project is coordinated by Kaunas University of Technology (leader D. Martuzevicius), IMC is partnering Institution, Leader of the Partner IMC R. Aldonyte.
  • Projects funded by European Union’s Horizon H2020 research and innovation programme:
  1. The HBM4EU project, Human Biomonitoring for EU, funded under the grant agreement No 733032. (2017-2022) EC funding: 50 mln. €, total budget – 75 mln. €. Leader of the Partner IMC R. Aldonyte.
  2. Horizon 2020 Call: H2020-NMBP-TR-IND-2018-2020 (TRANSFORMING EUROPEAN INDUSTRY): ElectroMechanoActive Polymer-based Scaffolds for Heart-on-Chip, 2020-2024. Total budget 5.356.096 €; IMC Partner 736.250 €. Coordinator: Dr. Christian Bergaud; Centre National de la Recherche Scientifique CNRS (CNRS) FR; Leader of IMC partner Dr. E. Bernotiene.

Contacts:

Head of Department of Regenerative Medicine: Dr. Eiva Bernotiene.

Phone: (+370) 5 2626049; +37068377130, e-mail: eiva.bernotiene@imcentras.lt>

The e-mail addresses of the employees are based on the principle: name.surname@imcentras.lt

Chief Researcher

Senior Researcher

Junior Researcher

PhD Candidate

Senior Researcher

Researcher

Junior Researcher

Senior Researcher

Researcher

Junior Researher, PhD Candidate
PhD Eiva Bernotiene Head of Department, Chief Researcher
Prof. Ali Mobasheri Chief Researcher
PhD Edvardas Bagdonas Senior Researcher
PhD Daiva Bironaite Senior Researcher
PhD Ruta Aldonyte Senior Researcher
Ausra Unguryte Researcher
PhD Ilona Uzieliene Researcher
PhD Sandra Meidutė – Abaravičienė Researcher
PhD Jaroslav Denkovskij Junior Researcher
PhD Jovile Raudoniute Junior Researcher
Rokas Miksiunas Junior Researcher
Ursule Kalvaityte Junior Researcher, PhD Candidate
Raminta Vaiciuleviciute PhD Candidate
Viktorija Aleksiuk PhD Candidate
Jolita Tamulevičienė Senior Laboratory Assistant
Roma Grinienė Senior Laboratory Assistant