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Department of Stem Cell Biology

PhD Augustas Pivoriūnas

Head of Department, Chief Researcher
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PhD Augustas Pivoriūnas

Head of Department, Chief Researcher

Education

 1998, Medical doctor degree, Vilnius University.
The topic and institution of the defended work 2004, defence of Doctoral thesis ‘‘The influence of different signaling pathways on the regulation of the cell cycle inhibitor p21 in differentiating human leukemic cells ’’. Vilnius University, Institute of Biochemistry.
Employment State Research Center for Innovative Medicine. Head of Department of Stem Cell Biology
Publications 1. A. Pivoriūnas, A. Verkhratsky. Astrocyte-derived extracellular vesicles mediate intercellular communications of the neurogliovascular unit. Neural Regen Res. 2021 Jul;16(7):1421-1422. doi: 10.4103/1673-5374.300994.
2. A. Verkhratsky, M. Augusto-Oliveira, A. Pivoriūnas, A. Popov, A. Brazhe, A. Semyanov. Astroglial asthenia and loss of function, rather than reactivity, contribute to the ageing of the brain. Pflugers Arch. 2020 Sep 26. doi: 10.1007/s00424-020-02465-3.
3. P. Andjus, M. Kosanović, K. Milićević, M. Gautam, S. Vainio, D. Jagečić, E. Kozlova, A. Pivoriūnas, J. Chachques, M. Sakaj, G. Brunello, D. Mitrecic, B. Zavan. Extracellular Vesicles as Innovative Tool for Diagnosis, Regeneration and Protection against Neurological Damage. Int J Mol Sci.2020 Sep 18; 21 (18):6859.  doi: 10.3390/ijms21186859.
4. K.Kriaučiūnaitė, A. Kaušylė, J.Pajarskienė, V. Tunaitis, D. Lim, A.Verkhratsky, A.Pivoriūnas. Immortalised hippocampal astrocytes from 3xTG-AD mice fail to support BBB integrity in vitro: role of extracellular vesicles in glial-endothelial communication. Cell Mol Neurobiol. 2020 May 22. doi: 10.1007/s10571-020-00871-w.
5. K. Narbute, V.Pilipenko, J. Pupure, T. Klinovičs, J.Auders , U. Jonavičė , K. Kriaučiūnaitė, A.Pivoriūnas, V. Kluša. Time-dependent memory and gait improvement by intranasally-administered extracellular vesicles in Parkinson’s disease model rats.  Cell Mol Neurobiol. 2020 May 14. doi: 10.1007/s10571-020-00865-8.
6. T.Matijošius, A. Pivoriūnas,  A. Čebatariūnienė, V. Tunaitis, L. Staišiūnas, G. Stalnionis, A. Ručinskienė, Svajus J. Asadauskas. Friction reduction using Nanothin Titanium layers on anodized aluminum as potential bioceramic material. Ceramics International. doi: 10.1016/j.ceramint.2020.03.105
7.  A. Verkhratsky, J. Rodrigues, A. Pivoriunas, R. Zorec, A. Semyanov. Astroglial atrophy in Alzheimer’s disease. Pflugers Arch. 2019 Oct;471(10):1247-1261. doi: 10.1007/s00424-019-02310-2. Epub 2019 Sep 13.
8.  A.Čebatariūnienė, K. Kriaučiūnaitė, J.Prunskaitė,V. Tunaitis and A.Pivoriūnas. Extracellular vesicles suppress basal and Lipopolysaccharide-induced NFκB activity in human periodontal ligament stem cells. Stem Cells and Development. 2019 Aug 1;28(15):1037-1049. doi: 10.1089/scd.2019.0021.
9. K. Narbute, V. Piļipenko, J. Pupure, Z. Dzirkale, U. Jonavičė, V. Tunaitis, K. Kriaučiūnaitė,  A. Jarmalavičiūtė, B. Jansone, V. Klusa, A. Pivoriūnas. Intranasal administration of extracellular vesicles derived from human teeth stem cells improve motor symptoms and normalize tyrosine hydroxylase expression in the substantia nigra and striatum of the 6-hydroxydopamine-treated rats. STEM CELLS Translational Medicine. 2019 May;8(5):490-499. doi:10.1002/sctm.18-0162.
10. U. Jonavičė, V. Tunaitis, K. Kriaučiūnaitė, A. Jarmalavičiūtė, A. Pivoriūnas. Extracellular vesicles can act as a potent immunomodulators of human microglial cells. J Tissue Eng Regen Med. 2019 Feb;13(2):309-318. doi: 10.1002/term.2810.
Projects Scientists from Department of Stem Cell Biology secured financing from EU structural funds (615053 Eur) for a new 4-year (2017-2021) project ,,Development of a new human pluripotent stem cell-based reporter assays for testing of anti-inflammatory and anti-oxidative properties of exosomes‘‘.
We are currently running project ,,In vitro modelling of human blood brain barrier pathology in Alzheimer’s disease‘‘. This project was financed from the EU structural funds (599459 Eur) and is implemented under The Global Grant measure.
Project duration 2017-2021.
Areas of interest, directions of cooperation

Stem cell biology, regenerative medicine, tissue engineering. From 2014 President of Lithuanian stem cell research association.

The main focus of Department of Stem Cell Biology is directed towards fundamental and applied stem cell research. This department consists of two main research groups. First one is Human Stem Cell Research Group, which focuses on the human mesenchymal stem cells (MSCs)-derived extracellular vesicles and neurodegenerative disease modeling in vitro. Second one is Animal Stem Cell Research Group, which concentrate on hematopoietic stem cells and in vivo studies.

Scientific research implemented in the department

HUMAN STEM CELL RESEARCH GROUP

MESENCHYMAL STEM CELL SECRETOME STUDIES

Bone marrow is first reported and most commonly used source of MSCs. There are many studies have shown therapeutic effect of MSCs obtained from other sources, including adipose tissue, dental pulp and umbilical cord. Our group isolated and characterized human MSCs from exfoliated deciduous teeth and periodontal ligament for the first time in Lithuania.

It is known that MSCs, isolated from different sources, have distinct properties and differentiation potential. Our group and other authors showed that MSCs from dental pulp display neurogenic properties and could be used for the neuroprotection.

Figure 1. Human MSCs from dental pulp.

Numbers of MSC-based clinical trials are increasing over time. Unfortunately, frequently the healing effects of these cells are not so good as anticipated. One of the possible reason is poor survival of transplanted cells. Despite of that many studies demonstrated beneficial therapeutic effects of MSCs.
New findings demonstrate the importance of paracrine mechanisms in the therapeutic action of MSCs. Extracellular vesicles (EVs) attracted a great deal of interest in recent years. Exosomes represent a subset of EVs, they are 30-120 nm in diameter, originate from multi-vesicular bodies and can transfer proteins, RNA, microRNA, lipids and metabolites between cells. Several studies addressed therapeutic potential of exosomes. We and others have demonstrated, that exosomes derived from human MSCs display neuroprotective, anti-inflammatory and immunosuppressive properties. Importantly, the composition and therapeutic properties of exosomes depends on cell type and its physiological state. Therefore, we need new and reliable screening tests for therapeutic efficacy of different exosomal preparations.
Scientists from Department of Stem Cell Biology secured financing from EU structural funds (615053 Eur) for a new 4-year (2017-2021) project ,,Development of a new human pluripotent stem cell-based reporter assays for testing of anti-inflammatory and anti-oxidative properties of exosomes‘‘. Gene editing technologies will be used to generate human inducible pluripotent stem cells (iPSC) NFkB and NRF2/1 reporter cell lines to test anti-inflammatory and anti-oxidative properties of exosomes. These iPSC NFkB and NRF2/1 reporter lines can be used for preclinical screening of other relevant pharmacological tools. Several scientific publications will be prepared and submitted to the international journals with high impact factor. There will be application for international patent of newly created cell lines.

Figure 2. Investigation of neuroprotective effect of exosomes on human dopaminergic neurons.

We expect that results obtained during the project will contribute to the development of stem cell technologies in Lithuania, as well as the development and implementation of new cell therapy protocols.

MODELLING ALZHEIMER’S DISEASE IN VITRO

New technologies that emerged during the last decade allow to generate patient-specific iPSCs. iPSCs can be used to develop disease model. A novel drug screening platforms open up new opportunities for the bio-pharmaceutical industry.

Figure 3. Neural stem cells from patient with familial AD

Progress in understanding Alzheimer’s disease (AD) has been hindered by a lack of suitable disease models, reflected in an inability to translate results from animal studies to successful human therapies. We are currently running project ,,In vitro modelling of human blood brain barrier pathology in Alzheimer’s disease‘‘. This project was financed from the EU structural funds (599459 Eur) and is implemented under The Global Grant measure.

Project duration 2017-2021. We are developing a relevant human cellular model to study the blood-brain barrier (BBB) in AD pathology. For this purpose we are establishing a human BBB co-culture model using astrocytes and brain endothelial cells derived from healthy controls and AD patients. This will represent a fundamentally novel approach to study human pathology using human cells. The proposed model can be applied for preclinical screening of relevant pharmacological tools. Project leader Prof. A. Verkhratsky is an internationally recognised scholar in the field of cellular neurophysiology.

ANIMAL STEM CELL RESEARCH GROUP
Figure 4. Quantum dots in MSCs from mouse.

Our group perform animal studies in vivo. Our studies provide valuable knowledge regarding the behaviour and in vivo properties of stem cells, which is particularly important for cell therapy. The anti-inflammatory effects and migratory properties of the hematopoietic stem cells isolated from mice have been evaluated using the contact hypersensitivity model. The impact of distinct populations of hematopoietic stem cells on the healing of wounds has also been established using a life-size skin wound model. We also tested the biocompatibility properties of some new materials and assessed the possibility that they could be used in biomedical ap-plications.

We also routinely isolate hematopoietic stem cells and MSCs from different laboratory animal lines. We are able to characterise, differentiat, evaluat metabolic activity and secretory factors of these cells. After stem cells evaluation in vitro, we transplant them to animal model. This technic help us to observe migration kinetics, ability to survive and regeneration capacity of stem cells in living organism conditions.

Topics of scientific research

PUBLICATIONS OF THE LAST 5 YEARS

1. A.Čebatariūnienė, A.Jarmalavičiūtė, V.Tunaitis, A.Pūrienė, A.Venalis, A.Pivoriūnas. Microcarrier culture enhances osteogenic potential of human periodontal ligament stromal cells. Journal of Cranio-Maxillofacial Surgery. 2017 Jun;45(6):845-854.
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2. A. Jarmalavičiūtė, A.Pivoriūnas. Neuroprotective properties of extracellular vesicles derived from mesenchymal stem cells. Neural Regenen Res. 2016 Jun;11(6):904-905.
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3. A. Jarmalavičiūtė, A.Pivoriūnas. Exosomes as a potential novel therapeutic tools against neurodegenerative diseases. Pharmacological Research. 2016.113(Pt B):816-822.
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4. V. Kašėta, A. Vaitkuvienė, A. Liubavičiūtė, R. Maciulevičienė, A Stirkė, G. Biziulevičienė. Quantitative evaluation of the transplanted lin- hematopoietic cell migration kinetics. Transplant Immunology. 2016; 34: 54-59.
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5. A. Jarmalavičiūtė, V.Tunaitis, U. Pivoraitė, A. Venalis, A.Pivoriūnas. Exosomes from dental pulp stem cells rescue human dopaminergic neurons from 6-hydroxy-dopamine-induced apoptosis. Cytotherapy. 2015;17 (7):932-939.
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6. U. Pivoraitė, A. Jarmalavičiūtė, V. Tunaitis, G. Ramanauskaitė, A. Vaitkuvienė, V. Kašėta, G. Biziulevičienė, A. Venalis, A. Pivoriūnas. Exosomes from human dental pulp stem cells suppress carragenaan-induced acute inflammation in mice. Inflammation. 2015; 38 (5): 1933-1941.
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7. A. Vaitkuviene, V. Ratautaite, A. Ramanaviciene, K. Sanen, R. Paesen, M. Ameloot, V. Petrakova, M. McDonald, F. Vahidpour, V. Kaseta, G. Ramanauskaitė, G. Biziuleviciene, M. Nesladek, A. Ramanavicius. Impact of diamond nanoparticles on neural cells. Molecular and Cellular Probes. 2015; 29: 25-30.
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8. A. Vaitkuviene, M. McDonald, F. Vahidpour, JP. Noben, K. Sanen, M. Ameloot, V. Ratautaite, V. Kaseta, G. Biziuleviciene, A. Ramanaviciene, M. Nesladek, A. Ramanavicius. Impact of differently modified nanocrystalline diamond on the growth of neuroblastoma cells. New Biotechnology. 2015; 32: 7-12.
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9. G. Ramanauskaitė, D. Žalalytė, V. Kašėta, A. Vaitkuvienė, L. Kalėdienė, G. Biziulevičienė. Skin extracellular matrix components accelerate the regenerative potential of Lin– cells. Central European Journal of Biology. 2014; 9 (4): 367-373.
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10. A. Vaitkuviene, V. Ratautaite, L. Mikoliunaite, V. Kaseta, G. Ramanauskaite, G. Biziule-viciene, A. Ramanaviciene, A. Ramanavicius. Some biocompatibility aspects of conducting polymer polypyrrole evaluated with bone marrow-derived stem cells. Colloids and Surfaces A: Physi-cochemical and Engineering Aspects. 2014; 442: 152–156.
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11. A. Jarmalavičiūtė, V. Tunaitis, E. Strainienė, R. Aldonytė, A. Ramanavičius, A. Venalis, K. E. Magnusson and A. Pivoriūnas. A New Experimental Model for Neuronal and Glial Differentiation Using Stem Cells Derived from Human Exfoliated Deciduous Teeth. J Mol Neurosci. 2013; 51 (2): 307-317.
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12. A. Vaitkuvienė, V.Kašėta, J. Voronovič, G. Ramanauskaitė, G. Biziulevičienė, A. Ramanavičienė, A. Ramanavičius. Evaluation of cytotoxicity of polypyrrole nanoparticles synthesized by oxidative polymerization. Journal of Hazardous Materials. 2013; 250-251: 167-174.

CURRENT PROJECTS

TITLE: IN VITRO MODELLING OF HUMAN BLOOD BRAIN BARRIER
PATHOLOGY IN ALZHEIMER’S DISEASE
LEADER: A.Verkhratsky
FUNDING: Operational programme for the European Union funds “Development of competences of scientists, other researchers and students through practical research activities”
DURATION: 2017-2021
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TITLE: DEVELOPMENT OF A NEW HUMAN PLURIPOTENT STEM CELL-BASED RE-PORTER ASSAYS FOR TESTING OF ANTI-INFLAMMATORY AND ANTI-OXIDATIVE PROPERTIES OF EXOSOMES
LEADER: A. Pivoriūnas
FUNDING: Operational programme for the European Union funds
“Targeted research in smart specialisation areas”
DURATION: 2017-2021
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TITLE: NEW THERAPEUTIC STRATEGIES FOR CHRONIC NEURODEGENERATIVE DISEASES USING EXOSOMES DERIVED FROM HUMAN STEM CELLS
LEADER: A. Pivoriūnas
FUNDING: National research programme “Healthy ageing”
DURATION: 2015-2018

Contacts

The email addresses of IMC employees are made as shown below (Lithuanian diacritics are not used):
First letter of the name.surname@imcentras.lt
If the employee has two names, the first letter of his/her first name is used in the email address.

Senior Researcher
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PhD Aida Kaušylė

Senior Researcher
Education Vilnius University Institute of Immunology – PhD, 2016
The topic and institution of the defended work In 2006 I defended my doctoral dissertation in the field of biomedical sciences “The role of 1,4-dihydropyridines in the regulation of inflammatory response” at the Institute of Immunology of Vilnius University.
Employment State Research Center for Innovative Medicine. Senior researcher
Publications
  1. Kriaučiūnaitė K, Kaušylė A, Pajarskienė J, Tunaitis V, Lim D, Verkhratsky A, Pivoriūnas A. Immortalised Hippocampal Astrocytes from 3xTG-AD Mice Fail to Support BBB Integrity In Vitro: Role of Extracellular Vesicles in Glial-Endothelial Communication, Cell Mol Neurobiol, 2020 May 22. doi: 10.1007/s10571-020-00871-w.
  2. Vytautas Kašėta, Aida Kaušylė, Justina Kavaliauskaitė, Monika Petreikytė, Arūnas Stirkė, Genė Biziulevičienė. Detection of intracellular biomarkers in viable cells using millisecond pulsed electric fields, Exp Cell Res, 2020, 389 (1), 111877.
  3. Ramanauskaite G, Vaitkuviene A, Kaseta V, Vitlipaite A, Liubaviciute A, Biziuleviciene G. Bone marrow-derived lineage-negative cells accelerate skin regeneration in vivo. Turk J Biol, 2018, 42, 205-212.
  4. Liubaviciute A, Kaseta V, Vaitkuviene A, Mackiewicz Z, Biziuleviciene G. Regenerative potential of partially differentiated mesenchymal stromal cells in a mouse model of a full-thickness skin wound. EXCLI Journal, 2018;17, 871-888.
  5. Kašėta V, Vaitkuvienė A, Liubavičiūtė A, Maciulevičienė R, Stirkė A, Biziulevičienė G. Quantitative evaluation of the transplanted lin− hematopoietic cell migration kinetics. Transplant Immunology, 2016, 34, 54-59.
  6. Vaitkuviene A, Ratautaite V, Ramanaviciene A, Sanen K, Paesen R, Ameloot M, Petrakova V, McDonald M, Vahidpour F, Kaseta V, Ramanauskaitė G, Biziuleviciene G, Nesladek M, Ramanavicius A. Impact of diamond nanoparticles on neural cells. Molecular and Cellular Probes, 2015, 29, 25-30.
  7. Vaitkuviene A, McDonald M, Vahidpour F, Noben JP, Sanen K, Ameloot M, RatautaiteV, Kaseta V, Biziuleviciene G, Ramanaviciene A, Nesladek M, Ramanavicius A. Impact of differently modified nanocrystalline diamond on the growth of neuroblastoma cells, New Biotechnology, 2015, 32, 7-12.
  8. Pivoraitė U, Jarmalavičiūtė A, Tunaitis V, Ramanauskaitė G, Vaitkuvienė A, Kašėta V, Biziulevičienė G, Venalis A, and Pivoriūnas A. Exosomes from human dental pulp stem cells suppress carragenaan-induced acute inflammation in mice. Inflammation, 2015, 38 (5): 1933-1941.
  9. Ramanauskaitė G, Žalalytė D, Kašėta V, Vaitkuvienė A, Kalėdienė L, Biziulevičienė G. Skin extracellular matrix components accelerate the regenerative potential of Lin– cells. Central European Journal of Biology, 2014, 9 (4): 367-373.
  10. Vaitkuviene A, Ratautaite V, Mikoliunaite L, Kaseta V, Ramanauskaite G, Biziuleviciene G, Ramanaviciene A, Ramanavicius A. Some biocompatibility aspects of conducting polymer polypyrrole evaluated with bone marrow-derived stem cells. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2014, 442, 152–156.
  11.  Vaitkuvienė A, Kašėta V, Voronovič J, Ramanauskaitė G, Biziulevičienė G, Ramanavičienė A, Ramanavičius A. Evaluation of cytotoxicity of polypyrrole nanoparticles synthesized by oxidative polymerization. Journal of Hazardous Materials, 2013, 250-251: 167-174.
  12. Ramanauskaitė G, Kašėta V, Vaitkuvienė A, Biziulevičienė G. Skin regeneration with bone marrow-derived cell populations. International Immunopharmacology, 2010, 10, 1548–1551.
  13. Biziulevičienė G, Kašėta V, Ramanauskaitė G, Vaitkuvienė A. Investigation of unmatured hematopoietic cell migration in a mouse model. Central European Journal of Biology, 2010, 5 (5): 585-589.
  14. Vaitkuvienė A, Kašėta V, Ramanauskaitė G, Biziulevičienė G. Cytotoxicity of the pharmaceutical and cosmetic gel-forming polymers, preservatives and glycerol on primary murine cell cultures. Acta Medica Lituanica, 2009, 16 (3-4): 92-97.
  15. Kašėta V, Biziulevičienė G, Ramanauskaitė G, Vaitkuvienė A, Biziulevičius GA. Magnetic cell sorting isolation of therapeutically effective BALB/c mouse bone marrow hematopoietic stem cell population, Biologija, 2008, 54 (4): 269–273.
  16. Biziulevičius GA, Vaitkuvienė A. Taking advantage of the experience in ethnomedicinal use of mushrooms: Anti-inflammatory and related pharmacological activities of fly agaric (Amanita muscaria) ethanolic extract deserve a modern evaluation. Medical Hypotheses, 2007, 69, 946-947.
  17. Vaitkuvienė A, Liutkevičius E, Biziulevičienė G, Ulinskaitė A, Darinskas A, Meškys R. Influence of 1,4-dihydropyridine derivatives on rat paw edema, biosynthesis of glucocorticoid hormone and its binding activity to glucocorticoid receptor. Biologija, 2006, 3, 96-101.
  18. Vaitkuvienė A, Ulinskaitė A, Meškys R, Duburs G, Kluša V, Liutkevičius E. Study of the interaction of 1,4-dihydropyridine derivatives with glucocorticoid hormone receptors from rat liver. Pharmacological Reports, 2006, 58, 551-558.
  19. Vaitkuvienė A, Biziulevičienė G, Ulinskaitė A, Liutkevičius E. Protective effect of a 1,4-dihydropyridine derivative in a model of mouse paw edema. Biologija, 2004, 2, 102-104.
  20. Ulinskaitė A, Mikalauskienė G, Vaitkuvienė A, Liutkevičius E. Studies of transcortin and of conformational changes in cytoplasmic glucocorticoid receptors in the lymphocytes of healthy and BLV-infected cows. Biologija, 2000, 2, 232-234.
Projects 1. European Union Structural Funds Grant “Development of competences of scientists, other researchers and students through practical research activities” Nr. 09.3.3-LMT-K-712-01-0082 “In vitro modelling of human blood brain barrier pathology in Alzheimer’s disease”; 2017-2021.
2. European Union Structural Funds Grant “Development of Competences of Scientists, Other Researchers And Students Through Practical Research Activities” Project No. 09.3.3-LMT-K-712-09-0234 “Influence of the different origin mitochondria on the metabolic activity of mesenchymal stem cells”; 2018.
3. European Union Structural Funds Grant “Support for scientific research by scientists and other researchers (Global Grant)” No. VP1-3.1-ŠMM-07-K-03-016 „Fundamental and applied studies of human mesenchymal stem cell secretome“; 2014-2015.
4. European Union Structural Funds Grant ”Postdoctoral Fellowship Implementation in Lithuania” within the framework of the Measure for Enhancing Mobility of Scholars and Other Researchers and the Promotion of Student Research (VP1-3.1-ŠMM-01) of the Program of Human Resources Development Action Plan. “Stem cell integration into synthetic polymeric matrices”, Agreement No 68/MTDS-130000-2025; 2010-2012.
5. Lithuanian State Science and Studies Foundation Grant No C-07023 „Fundamental research of stem cell function mechanisms“. Cytotherapy 2; Agreement No P-23/04; 2006-2009.
6. Lithuania Science Foundation Grant No C-04/2007 „Stem cell integration, survival and functional efficiency of stem cells in the pathological lesion. Preclinical study“ further research continuation; 2007.
7. Lithuanian State Science and Studies Foundation Project No G-41/07 „Studies of gel-forming polymer and cell interactions in vitro“, No 07/03; 2007.
8. Lithuania Science Foundation Grant No.U-04001 „Stem cell integration, survival and functional efficiency of stem cells in the pathological lesion. Preclinical study“; Investigator (Section of Institute of Immunology), 2004-2006.
Areas of interest, directions of cooperation

Stem cells, biocompatible, biologically active substances.

 

PhD Candidate
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Barbora Lekešytė

PhD Candidate
Education Bachelor’s degree from Middlesex University, United Kingdom
Master’s degree from National University Ireland Galway, Ireland
The topic and institution of the defended work 1.‘The effect of vegetation on Drosera ‘prey’ on Lundy island’ – Middlesex University, United Kingdom
2.‘Potential neuro-protective role of extracellular vesicles and N-Acetyl Cysteine in an in vivo model of neurodegeneration’ – National University Galway, Ireland
Employment ‘Investigation of the therapeutic effects of extracellular vesicles in human neuroglia and neuron cells’.
Publications What’s on the menu: Drosera rotundifolia diet determination using DNA data. B.Lekesyte, S.Kett and M.J.T.N Timmermans. Journal of the Lundy Field Society, 6, 27-36, 2018.
Areas of interest, directions of cooperation
  1. Stem cells or stem cells – derived exosomes in neurodegenerative diseases;
  2. Electrophysiology in neuroscience

Senior Researcher
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PhD Virginijus Tunaitis

Senior Researcher

Education

 Vilnius University, Ph.D. Biomedical sciences, biology, Vilnius 2011
The topic and institution of the defended work Dissertation: Analysis of in vitro functions of mesenchymal stem cells isolated from different human tissues
Employment 2019-present State Research Institute Center for Innovative Medicine, Senior research associate
Publications 1. Matijošius,  T., Pivoriūnas, A., Čebatariūnienė, A., Tunaitis, V.,  Staišiūnas, L., Stalnionis, G., Ručinskienė, A. Asadauskas, S.J. (2020). Friction reduction using Nanothin Titanium layers on anodized aluminum as potential bioceramic material. Ceramics International, 46(10): 15581-15593.
2. Kriaučiūnaitė K., Kaušylė A., Pajarskienė J., Tunaitis V., Lim D., Verkhratsky A., Pivoriūnas A. (2020). Immortalised Hippocampal Astrocytes from 3xTG-AD Mice Fail to Support BBB Integrity In Vitro: Role of Extracellular Vesicles in Glial-Endothelial Communication. Cell Mol Neurobiol, 2020 May 22. doi: 10.1007/s10571-020-00871-w. Online ahead of print.
3. Čebatariūnienė A, Kriaučiūnaitė K, Prunskaitė J, Tunaitis V, Pivoriūnas A. Extracellular Vesicles Suppress Basal and Lipopolysaccharide-Induced NFκB Activity in Human Periodontal Ligament Stem Cells. Stem Cells Dev. 2019 Aug 1;28(15):1037-1049. doi: 10.1089/scd.2019.0021.
4. Narbute K, Piļipenko V, Pupure J, Dzirkale Z, Jonavičė U, Tunaitis V, Kriaučiūnaitė K, Jarmalavičiūtė A, Jansone B, Kluša V, Pivoriūnas A. Intranasal Administration of Extracellular Vesicles Derived from Human Teeth Stem Cells Improves Motor Symptoms and Normalizes Tyrosine Hydroxylase Expression in the Substantia Nigra and Striatum of the 6-Hydroxydopamine-Treated Rats. Stem Cells Transl Med. 2019 May;8(5):490-499. doi: 10.1002/sctm.18-0162.
5. Jonavičė U, Tunaitis V, Kriaučiūnaitė K, Jarmalavičiūtė A, Pivoriūnas A. Extracellular vesicles can act as a potent immunomodulators of human microglial cells. J Tissue Eng Regen Med. 2019 Feb;13(2):309-318. doi: 10.1002/term.2810.
6. Trumpaitė-Vanagienė R, Čebatariūnienė A, Tunaitis V, Pūrienė A, Pivoriūnas A. Live cell imaging reveals different modes of cytotoxic action of extracts derived from commonly used luting cements. Arch Oral Biol. 2018 Feb;86:108-115. doi: 10.1016/j.archoralbio.2017.11.011.
7. Čebatariūnienė A, Jarmalavičiūtė A, Tunaitis V, Pūrienė A, Venalis A, Pivoriūnas A. Microcarrier culture enhances osteogenic potential of human periodontal ligament stromal cells. .J Craniomaxillofac Surg. 2017 Jun;45(6):845-854. doi: 10.1016/j.jcms.2017.03.009.
8. Jarmalavičiūtė A, Tunaitis V, Pivoraitė U, Venalis A, Pivoriūnas A. Exosomes from dental pulp stem cells rescue human dopaminergic neurons from 6-hydroxy-dopamine-induced apoptosis. Cytotherapy. 2015 Jul;17(7):932-9. doi: 10.1016/j.jcyt.2014.07.013.
9. Pivoraitė U, Jarmalavičiūtė A, Tunaitis V, Ramanauskaitė G, Vaitkuvienė A, Kašėta V, Biziulevičienė G, Venalis A, Pivoriūnas A. Exosomes from Human Dental Pulp Stem Cells Suppress Carrageenan-Induced Acute Inflammation in Mice. Inflammation. 2015 Oct;38(5):1933-41. doi: 10.1007/s10753-015-0173-6.
10. Jarmalavičiūtė, V. Tunaitis, E. Strainienė, R. Aldonytė, A. Ramanavičius, A. Venalis, K.-E. Magnusson, A. Pivoriūnas. A new experimental model for neuronal and glial differentiation using stem cells derived from human exfoliated deciduous teeth. Journal of Molecular Neuroscience. 2013. 51(2): 307-317. doi: 10.1007/s12031-013-0046-0.
11. Tunaitis V, Borutinskaitė V, Navakauskienė R, Treigytė G, Ungurytė A, Aldonytė R, Magnusson K-E, Pivoriūnas A. Effects of different sera on adipose tissue-derived mesenchymal stromal cells. Journal of Tissue Engineering and Regenerative Medicine, 2011 Oct;5(9): 733–46. doi: 10.1002/term.374.
12. Savickienė J, Treigytė G, Vistartaitė G, Tunaitis V, Magnusson KE, Navakauskienė R. C/EBPα and PU.1 are involved in distinct differentiation responses of acute promyelocytic leukemia HL-60 and NB4 cells via chromatin remodeling. Differentiation. 2011 Jan;81(1):57-67. doi: 10.1016/j.diff.2010.08.003.
13. Aldonytė R, Tunaitis V, Surovas A, Suriakaitė K, Jarmalavičiutė A, Magnusson K-E, Pivoriunas A. Effects of major human antiprotease alpha-1-antitrypsin on the motility and proliferation of stromal stem cells from human exfoliated deciduous teeth. Regenerative Medicine, 2010 Jul;5(4):633-43. doi: 10.2217/rme.10.18.
14. Pivoriūnas A, Surovas A, Borutinskaitė V, Matuzevičius D, Treigytė G, Savickienė J, Tunaitis V, Aldonytė R, Jarmalavičiūtė A, Suriakaitė K, Liutkevičius E, Venalis A, Navakauskas D, Navakauskienė R, Magnusson K-E. Proteomic analysis of stromal cells derived from the dental pulp of human exfoliated deciduous teeth. Stem Cells and Development, 2010 Jul;19(7):1081-93. doi: 10.1089/scd.2009.0315.
15. Tunaitis V, Sadzevičienė I, Suriakaitė K, Surovas A, Aldonytė R, Magnusson K-E, Pivoriūnas A.; 2008; Expression and subcellular localization of histone deacetylases in mesenchymal stem-like cells from exfoliated deciduous teeth. Biologija; 54 (4); 306–311.
16. Pivoriūnas A, Savickienė J, Treigytė˙G, Tunaitis V, Navakauskienė R, Magnusson K-E. 2007.  PI 3-K signaling pathway suppresses PMA-induced expression of p21WAF1/Cip1 in human leukemia cells. Molecular and Cellular Biochemistry. 2007 Aug;302(1-2):9-18. doi:10.1007/s11010-007-9419-4.
Projects 1. Prof. A.Verkhratsky. “Alzheimerio ligą lydinčių hematoencefalinio barjero pažeidimų modeliavimas in vitro” Mokslininkų inicijuoti projektai (Aukšto lygio MTEP). 2017-2021 metai. Bendra skirtų lėšų suma 599459,33 eur.
2. Dr. A. Pivoriūnas. “Naujos žmogaus pliuripotentinių kamieninių ląstelių reporterių linijos priešuždegiminio ir antioksidacinio egzosomų poveikio įvertinimui” Valstybės užsakomieji tyrimai – Aukšto lygio MTEP (SMART). 2017-2021 metai. Bendra skirtų lėšų suma 642622,97 eur.
3. Dr. A. Pivoriūnas. „Žmogaus kamieninių ląstelių egzosomų panaudojimas kuriant naujus lėtinių neurodegeneracinių ligų terapijos metodus” Nacionaline mokslo programa „Sveikas senėjimas“. Projekto trukmė 2015-2018 metai. Bendra skirtų lėšų suma 200000 eur.
4. Dr. A. Pivoriūnas. „Nervinės diferenciacijos modelio sukūrimas, panaudojant žmogaus dantų pulpos kamienines ląsteles“  Lietuvos mokslo tarybos finansuojamas projektas. Projekto trukmė 2011-2012. Bendra skirtų lėšų suma 178900 Lt
5. Prof A.Venalis “Fundamentiniai ir taikomieji žmogaus mezenchiminių kamieninių ląstelių sekretomo tyrimai”. Visuotinės dotacijos priemonė. Projektas finansuojamas Europos socialinio fondo (ESF) lėšomis pagal Žmogiškųjų išteklių plėtros veiksmų programą. Projekto trukmė 2013-2015 metai. Bendra skirtų lėšų suma 996674,22Lt.
6. Prof. M.Burnier „Possible Interaction of Endogenous Sodium Pump Inhibitors and Genetic Factors in the Development of Salt-sensitive Hypertension“ SCOPES programa (Scientific co-operation between Eastern Europe and Switzerland) Projekto trukmė 2009-2013 metai. Bendra skirtų lėšų suma 195000 Lt
7. Prof. habil. dr. J. Dadonienė  „Suaugusio žmogaus mezenchiminių kamieninių làstelių paruošimo terapiniams tikslams technologijos“. Valstybinis mokslo ir studijų fondas. Aukštųjų technologijų plėtros 2007-2013 metų programa. Biotechnologijos kryptis. 2007-2009. vertė 975000 Lt
8. Prof. habil. dr. A. Laucevičius  „Fundamentiniai kamieninių ląstelių funkcionavimo mechanizmų tyrimai“ Valstybinis mokslo ir studijų fondas. Prioritetinių Lietuvos mokslinių tyrimų ir eksperimentinės plėtros krypčių projektai. Genomika ir biotechnologijos sveikatai ir žemės ūkiui. 2007-2009. Vertė 936503 Lt
9. Dr. E. Bernotienė Nacionalinis kamieninių ląstelių centras.. Europos Sąjungos struktūrinių fondų  BPD 1 prioriteto 5 priemonė. 2005-2008 vertė  3 872 990,00 Lt.
10. Prof., habil. dr. Algirdas Venalis „Mokslinės visuomenės žinių plėtojimas kamieninių ir aukštesnės diferenciacijos ląstelių tyrimų srityje“ Europos Sąjungos struktūrinių fondų  BPD 2 prioriteto 2.5 priemonė „Žmogiškųjų išteklių kokybės gerinimas mokslinių tyrimų ir inovacijų srityje“. 2005-2008  vertė 1 128 630,00  Lt.
Areas of interest, directions of cooperation

Stem cell biology, therapeutic applications of human stem cells, regulation of gene activity, inflammation, developmental biology, tissue engineering, extracellular vesicles, neurodegenerative diseases.

Researcher
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PhD Ugnė Jonavičė

Researcher
Education 2014 – 2018 PhD. Natural sciences, Biology, State Research Institute Centre for Innovative Medicine, Department of stem cell biology.
2012 – 2014 Nano biotechnologies master studies, Vilnius Gediminas technical university, Faculty of fundamental sciences.
2008 – 2012 Conservation and restoration chemistry bachelor studies, Vilnius university, Faculty of chemistry.
The topic and institution of the defended work „Fundamental and applied studies of human mesenchymal stem cell secretome „; State Research Institute Centre for Innovative Medicine
Employment 2019 October – now. Researcher, State Research Institute Centre for Innovative Medicine, Department of stem cell biology.
2015 June – 2019 October. Junior researcher, State Research Institute Centre for Innovative Medicine, Department of stem cell biology.
2014 January – 2015 June. Senior laboratory assistant, State Research Institute Centre for Innovative Medicine, Department of stem cell biology.
Projects LMT-DOT6 “Development of a new human pluripotent stem cell-based reporter assays for testing of anti-inflammatory and anti-oxidative properties of exosomes” 2017-2021
“In vitro modelling of human blood brain barrier pathology in Alzheimer’s disease” 2017-2021
Areas of interest, directions of cooperation Dental pulp stem cells extracellular vesicles, cellular therapy,microglia, migration neuroinflammation, neurodegenerative diseases.

PhD Candidate
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Justina Pajarskienė

PhD Candidate

Education

 Master of Technological Sciences
The topic and institution of the defended work The Use Of Reporter Cell Lines For Study Of The Effects Of Extracellular Vesicles, VILNIUS TECH
Employment PhD student, laboratory technitian
Publications 1.      Kriaučiūnaitė, K., Kaušylė, A., Pajarskienė, J., Tunaitis, V., Lim, D., Verkhratsky, A., & Pivoriūnas, A. (2020). Immortalised hippocampal astrocytes from 3xTG-AD mice fail to support BBB integrity in vitro: role of extracellular vesicles in glial-endothelial communication. Cellular and Molecular Neurobiology, 1-12.
2.      Kriauciunaite, K., Pociute, A., Kausyle, A., Pajarskiene, J., Verkhratsky, A., & Pivoriunas, A. (2021). Concentration-dependent duality of bFGF in regulation of barrier properties of human brain endothelial cells. bioRxiv.
3.      Čebatariūnienė, A., Kriaučiūnaitė, K., Prunskaitė, J., Tunaitis, V., & Pivoriūnas, A. (2019). Extracellular vesicles suppress basal and lipopolysaccharide-induced NFκB activity in human periodontal ligament stem cells. Stem cells and development, 28(15), 1037-1049.
Projects „Development of a new human pluripotent stem cell-based reporter assays for testing of anti-inflammatory and anti-oxidative properties of exosomes “
Areas of interest, directions of cooperation

Cell Culture, Signalling Pathways, Stem Cells, Extracellular Vesicles,

Reporter Assay

Senior Researcher
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PhD Vytautas Kašėta

Senior Researcher

Education

 2004 B. S. Biology.Vilnius University, Lithuania.
2006 M. S. Biology.Vilnius University, Lithuania.
2011 Ph. D. Biomedicine. State Research Institute Centre for Innovative Medicine; Vilnius University, Lithuania
The topic and institution of the defended work Investigation of Bone Marrow Hematopoietic Stem Cell Migration during Inflammation in BALB/c Mice. State Research Institute Centre for Innovative Medicine; Vilnius University.
Employment 2020 – present Vilnius University, Senior Researcher
2017 – present State Research Institute Centre for Innovative Medicine, Senior Researcher
2016 – present Vilnius University, Associate Professor
2014  Vilnius University, Faculty of Medicine, Department of Pathology, Forensic Medicine and Lecturer Pharmacology, Lithuania
Publications
  1. Kašėta V, Kaušylė A, Kavaliauskaitė J, Petreikytė M, Stirkė A, Biziulevičienė G. Detection of intracellular biomarkers in viable cells using millisecond pulsed electric fields. Exp Cell Res, 2020, 389(1):111877.
  2. Ramanauskaite G, Vaitkuviene A, Kaseta V, Vitlipaite A, Liubaviciute A, Biziuleviciene G. Bone marrow-derived lineage-negative cells accelerate skin regeneration in vivo. Turk J Biol, 2018, 42, 205-212.
  3. Liubaviciute A, Kaseta V, Vaitkuviene A, Mackiewicz Z, Biziuleviciene G. Regenerative potential of partially differentiated mesenchymal stromal cells in a mouse model of a full-thickness skin wound. EXCLI Journal, 2018;17, 871-888.
  4. Simonis P, Kersulis S, Stankevich V, Kaseta V, Lastauskiene E, Stirke A. Caspase dependent apoptosis induced in yeast cells by nanosecond pulsed electric fields. Bioelectrochemistry. 2017, 115:19-25.
  5. Kašėta V, Vaitkuvienė A, Liubavičiūtė A, Maciulevičienė R, Stirkė A, Biziulevičienė G. Quantitative evaluation of the transplanted lin− hematopoietic cell migration kinetics. Transplant Immunology, 2016, 34, 54-59.
  6. Vaitkuviene A, Ratautaite V, Ramanaviciene A, Sanen K, Paesen R, Ameloot M, Petrakova V, McDonald M, Vahidpour F, Kaseta V, Ramanauskaitė G, Biziuleviciene G, Nesladek M, Ramanavicius A. Impact of diamond nanoparticles on neural cells. Molecular and Cellular Probes, 2015, 29, 25-30.
  7. Vaitkuviene A, McDonald M, Vahidpour F, Noben JP, Sanen K, Ameloot M, RatautaiteV, Kaseta V, Biziuleviciene G, Ramanaviciene A, Nesladek M, Ramanavicius A. Impact of differently modified nanocrystalline diamond on the growth of neuroblastoma cells, New Biotechnology, 2015, 32, 7-12.
  8. Pivoraitė U, Jarmalavičiūtė A, Tunaitis V, Ramanauskaitė G, Vaitkuvienė A, Kašėta V, Biziulevičienė G, Venalis A, and Pivoriūnas A. Exosomes from human dental pulp stem cells suppress carragenaan-induced acute inflammation in mice. Inflammation, 2015, 38 (5): 1933-1941.
  9. Ramanauskaitė G, Žalalytė D, Kašėta V, Vaitkuvienė A, Kalėdienė L, Biziulevičienė G. Skin extracellular matrix components accelerate the regenerative potential of Lin– cells. Central European Journal of Biology, 2014, 9 (4): 367-373.
  10. Vaitkuviene A, Ratautaite V, Mikoliunaite L, Kaseta V, Ramanauskaite G, Biziuleviciene G, Ramanaviciene A, Ramanavicius A. Some biocompatibility aspects of conducting polymer polypyrrole evaluated with bone marrow-derived stem cells. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2014, 442, 152–156.
  11. Vaitkuvienė A, Kašėta V, Voronovič J, Ramanauskaitė G, Biziulevičienė G, Ramanavičienė A, Ramanavičius A. Evaluation of cytotoxicity of polypyrrole nanoparticles synthesized by oxidative polymerization. Journal of Hazardous Materials, 2013, 250-251: 167-174.
  12. Ramanauskaitė G, Kašėta V, Vaitkuvienė A, Biziulevičienė G. Skin regeneration with bone marrow-derived cell populations. International Immunopharmacology, 2010, 10, 1548–1551.
  13. Biziulevičienė G, Kašėta V, Ramanauskaitė G, Vaitkuvienė A. Investigation of unmatured hematopoietic cell migration in a mouse model. Central European Journal of Biology, 2010, 5 (5): 585-589.
  14. Vaitkuvienė A, Kašėta V, Ramanauskaitė G, Biziulevičienė G. Cytotoxicity of the pharmaceutical and cosmetic gel-forming polymers, preservatives and glycerol on primary murine cell cultures. Acta Medica Lituanica, 2009, 16 (3-4): 92-97.
  15. Kašėta V, Biziulevičienė G, Ramanauskaitė G, Vaitkuvienė A, Biziulevičius GA. Magnetic cell sorting isolation of therapeutically effective BALB/c mouse bone marrow hematopoietic stem cell population, Biologija, 2008, 54 (4): 269–273.
Projects
  1. European Union funds. Program “Development of scientific competence of scientists, other researchers and students through practical scientific activities” No 09.3.3.-LMT-K-712-17-0008 “Search of chronoepigenetic markers of schizophrenia”; 2020–2023.
  2. European Union funds “Targeted research in smart specialisation areas” No 01.2.2-LMT-K-718-01-0012 “Development of a new human pluripotent stem cell-based reporter assays for testing of anti-inflammatory and antioxidative properties of exosomes”; 2017–2021.
  3. European Union funds.” Program “Development of scientific competence of scientists, other researchers and students through practical scientific activities”. “Investigation of exogenous mitochondrial properties and their effect on mesenchymal stem cells” 2018. No. 09.3.3-LMT-K-712-09-0241.
  4. Joint Lithuanian-Latvian-Taiwanese Tripartite Cooperation Programme, „Mesenchymal stem cell and cancer stem-like cell response to nanoparticle treatment“. Grant No.TAP-LLT-13-016; 2014–2016.
  5. European Union Structural Funds project ”Postdoctoral Fellowship Implementation in Lithuania” within the framework of the Measure for Enhancing Mobility of Scholars and Other Researchers and the Promotion of Student Research (VP1-3.1-ŠMM-01) of the Program of Human Resources Development Action Plan. “Research of stem and cancer cells interfaces: targeted delivery of nanoparticles to the tumor”, Agreement No 004/22. 2012–2014.
  6. European Union funds.” Program “Development of scientific competence of scientists, other researchers and students through practical scientific activities”. “Influence of Nanoparticles on Stem Cell Migration in a Wound Model”. 2013. PR2013-13/SMT13R-036.
  7. MITA project: High technology development programme: Nanoelectroporator for biological cells, BIOnanopore, 2011–2013.
  8. Lithuanian State Science and Studies Foundation project: „Fundamental research of stem cell function mechanisms“. Cytotherapy 2; Reg. No C-07023; Agreement No P-23/04. 2006–2009.
  9. Lithuania Science Foundation Grant No C-04/2007 „Stem cell integration, survival and functional efficiency of stem cells in the pathological lesion. Preclinical study“ further research continuation; 2007.
  10.   Lithuania Science Foundation Grant No.U-04001 „Stem cell integration, survival and functional efficiency of stem cells in the pathological lesion. Preclinical study“ Cytotherapy. 2004–2006.
Areas of interest, directions of cooperation Biomedicine, Immunology, Stem Cells, Mitochondria, Nanoparticles, Migration, Immunotherapy.

Junior Researcher
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PhD Karolina Kriaučiūnaitė

Junior Researcher

Education

 Higher Education
The topic and institution of the defended work Neuroprotective Effect of Mesenchymal Stem Cell-Derived extracellular Vesicles
Employment State Research Institute Center for Innovative Medicine, Junior researcher
Publications
  1. Kriaučiūnaitė, K., Kaušylė, A., Pajarskienė, J., Tunaitis, V., Lim, D., Verkhratsky, A., Pivoriūnas, A. “Immortalised hippocampal astrocytes from 3xTG-AD mice fail to support BBB integrity in vitro: Role of extracellular vesicles in glial-endothelial communication”. Cellular and Molecular Neurobiology, 2020, 1-12.
  2. Narbute, K., Pilipenko, V., Pupure, J., Klinovičs, T., Auders, J., Jonavičė, U., Kriaučiūnaitė, K., Pivoriūnas, A., Kluša, V. “Time-Dependent Memory and Gait Improvement by Intranasally-Administered Extracellular Vesicles in Parkinson`s Disease Model Rats”. Cellular and molecular neurobiology, 2020.
  3. Jonavičė, U., Tunaitis, V., Kriaučiūnaitė, K., Jarmalavičiūtė, A., Pivoriūnas, A. “Extracellular vesicles can act as a potent immunomodulators of human microglial cells”. Journal of tissue engineering and regenerative medicine, 2019, 13.2: 309-318.
  4. Narbute, K., Piļipenko, V., Pupure, J., Dzirkale, Z., Jonavičė, U., Tunaitis, V., Kriaučiūnaitė, K., Jarmalavičiūtė, A.,Baiba, J., Kluša, V., Pivoriūnas, A.”Intranasal administration of extracellular vesicles derived from human teeth stem cells improves motor symptoms and normalizes tyrosine hydroxylase expression in the substantia nigra and striatum of the 6‐hydroxydopamine‐treated rats”. Stem cells translational medicine, 2019, 8.5: 490-499.
  5. Čebatariūnienė, A., Kriaučiūnaitė, K., Prunskaitė, J., Tunaitis, V., Pivoriūnas, A. „Extracellular vesicles suppress basal and lipopolysaccharide-induced NFκB activity in human periodontal ligament stem cells“. Stem cells and development, 2019, 28.15: 1037-1049.
Projects In vitro modelling of human blood-brain barrier pathology in Alzheimer’s disease (09.3.3-LMT-K-712)
Areas of interest, directions of cooperation Mesenchymal stem cells, induced pluripotent stem cells, astrocytes, blood-brain barrier, extracellular vesicles, exosomes, neurodegenerative models in vitro
PhD Augustas Pivoriūnas Head of Department, Chief Researcher
Prof PhD Alexei Verkhratsky  Chief Researcher
PhD Aida Kaušylė Senior Researcher
PhD Virginijus Tunaitis Senior Researcher
PhD Vytautas Kašėta Senior Researcher
PhD Ugnė Jonavičė Researcher
Karolina Kriaučiūnaitė Junior Researcher
Barbora Lekešytė PhD Candidate
Justina Pajarskienė PhD Candidate
Vilma Cholmatova Senior Laboratory Assistant
Diana Romenskaja Laboratory Assistant