We study the mechanisms of CNS diseases, brain and spinal cord injuries and neurodegenerative diseases. Using different types of stem cells (mesenchymal, neural and induced pluripotent), we aim to create in vitro 3D models suitable for drug testing and brain tumour research. We aim to enhance the therapeutic activity of mesenchymal stem cells by modulating their metabolism and 3D microenvironment. Another line of research focuses on the role of exosomes isolated from stem cells in the regeneration of the injured spinal cord, the development of brain aneurysms or the microenvironment of glioblastomas. We are also developing a novel diagnostic method using miRNAs to determine the severity of spinal cord injury in patients. We collaborate with chemists to develop polymers to promote injured tissue regeneration and develop materials for targeted drug delivery to glioblastoma and in vivo imaging. We are collaborating with Prof. James Fawcett at the University of Cambridge on neural tissue regeneration using viral vectors for gene transfer and manipulation of extracellular matrix (see Centre for Reconstructive Neuroscience).
Head of the Department
Assoc. Prof. Pavla Jendelová, PhD
Storage conditions affect the composition of the lyophilised secretome of multipotent mesenchymal stromal cells
The optimal preservation of mesenchymal stromal cell-derived secretome is crucial for its widespread use. The stability of biomolucules is highly affected by storage duration and temperature. We discovered that storage of lyophilised secretome at −80°C ensured biomolecule preservation for 3 and 30 months. Storage at −20°C, 4°C, or room temperature had a detrimental effect on growth factors and cytokines levels, which became more pronounced over time.
Effect of storage temperature and duration on the stability of lyophilised multipotent mesenchymal stromal cell-derived secretome composition. The conditioned medium from Wharton’s jelly MSCs was lyophilised and kept at −80°C, −20°C, 4°C, or room temperature for 3 and 30 months. After storage and reconstitution, the levels of growth factors and cytokines were assessed using multiplex assay. Short-term storage at various temperatures maintained over 60% of the studied growth factors and cytokines; long-term preservation was only adequate at −80°C.
Publication:
Rogulska, O., Vackova, I., Prazak, S., Turnovcova, K., Kubinova, S., Bacakova, L., Jendelova, P., Petrenko, Y.: (2024) Storage conditions affect the composition of the lyophilized secretome of multipotent mesenchymal stromal cells. Scientific reports. 14(1): 10243.
Low-dose hyaluronic acid synthase inhibitor increases neural tissue plasticity after chronic spinal cord injury but is not sufficient to reduce functional deficits
Rats with chronic spinal cord injury (SCI) were fed with hyaluronic acid syntase inhibitor (HASI) to promote neuroplasticity. HASI treatment reduced the gliar scar, HA synthesis and increased sprouting of 5-hydroxytryptamine fibres into ventral horns. However, the current dose was not sufficient to suppress CS-GAG up-regulation induced by SCI. Further adjustment of the dosage will be required to benefit functional recovery after SCI.
HASI treatment reduced glial scar area surrounding the lesion site. Representative fluorescence images showing the epicenter of the lesion stained for glial fibrillary acidic protein (GFAP) in the HASI and placebo treated group with chronic spinal cord injury. Squares show magnified images illustrating structural changes in glial scar after HASI treatment compared with untreated animals. Bar graph showing the area of glial scar around the central cavity.
Publication:
Štepánková K, Chudíčková M, Šimková Z, Martinez-Varea N, Kubinová Š, Urdzíková Machová L, Jendelová P, Kwok JCF. Low oral dose of 4-methylumbelliferone reduces glial scar but is insufficient to induce functional recovery after spinal cord injury. Sci Rep. 2023 Nov 6;13(1):19183. doi: 10.1038/s41598-023-46539-5.
Perineuronal nets affect memory and learning after synapse withdrawal
It has been proposed that the cavities in perineuronal nets (PNNs), which contain synapses, can act as a memory store and that they remain stable after synaptic withdrawal (SW) caused by anoxia or hibernation. We monitor place memory before and after SW. Synaptic withdrawal caused only mild memory deficit, which was not worsened by PNNs disruption. After SW, only animals lacking PNNs showed memory restoration and relearning. The results support a role for PNNs in learning, but not in long‑term memory storage.
Morris Water maze; effects of PNNs removal on memory before and after synapse withdrawal caused by hibernation-like state (HLS). All mice showed normal learning to find the platform (A). Chondroitinase (ChABC) dissolving PNNs was injected after initial training. Hibernated animals showed a partial loss of memory, but not to the level of naïve animals (B). During the relearning phase (C, D), animals in the HLS group did not show significant re-learning. However, animals treated with ChABC and HLS were fast relearners (D).
Publication:
Ružička, J., Dalecká, M., Šafránková, K., Peretti, D., Jendelová, P., Kwok, J.C.F., Fawcet, J.W.: (2022) Perineuronal nets affect memory and learning after synapse withdrawal. Translational Psychiatry. 12(1):480. doi: 10.1038/s41398-022-02226-z.
Involvement of mTOR Pathways in Recovery from Spinal Cord Injury by Modulation of Autophagy and Immune Response
We assessed the mechanisms of two mTOR pathway inhibitors, rapamycin and pp242, which influenced the spinal cord injury (SCI) in rats. We showed that treatment with rapamycin or pp242 caused inhibition of mTOR pathway, increased autophagy and modulate neuroinflammation in the spinal cord tissue after SCI. Our results suggest that treatment with pp242 was not more effective than rapamycin. We propose that benefits of mTOR inhibition in SCI treatment are mainly mediated through mTORC1.
Suppression of mTOR pathway by rapamycin or pp242 enhances autophagy in spinal cord injury. Immunohistochemical analysis of LC3b in spinal cord sections from rats treated with vehicle control (A), RAPA (B), or pp242 (C) revealed a significant increase in LC3b expression in both RAPA- and pp242-treated groups (D).
Scale bars: 500 µm; D.1, E.1, and F.1 images are 1:4 magnifications of corresponding areas of the spinal cord. Arrows point to examples of DAB-stained cells. Data are shown as means ± SEM; * p < 0.05, ** p < 0.01, *** p < 0.001.
Publication:
Vargová, I., Machová Urdziková, L., Karová, K., Smejkalová, B., Sursal, T., Cimermanová, V., Turnovcová, K., Gandhi, Ch.D., Jhanwar-Uniyal, M., Jendelová, P.: (2021) Involvement of mTOR Pathways in Recovery from Spinal Cord Injury by Modulation of Autophagy and Immune Response. Involvement of mTOR Pathways in Recovery from Spinal Cord Injury by Modulation of Autophagy and Immune Response. Biomedicines. 9(6): 593.
Projects
1. 5. 2025 – 31. 12. 2028
Role of kynurenines in the pathophysiology of the inflammatory response and vasospasm in patients with aneurysmal subarachnoid hemorrhage
Centre for Reconstructive NeuroscienceDoody N. E.Smith N. J.Akam E. C.Askew G. N.Kwok J. C. F.Ichiyama R. M.
2024
J Neurophysiol . 2024 Aug 1;132(2):531-543. doi: 10.1152/jn.00422.2023. Epub 2024 Jul 10.
Centre for Reconstructive NeuroscienceKirichuk O.Srimasorn S.Zhang X.Roberts A. R. E.Coche-Guerente L.Kwok J. C. F.Bureau L.Débarre D.Richter R. P.
2023
Langmuir . 2023 Dec 19;39(50):18410-18423. doi: 10.1021/acs.langmuir.3c02567. Epub 2023 Dec 4.
Centre for Reconstructive NeuroscienceMilton A. J.Kwok J. C. F.McClellan J.Randall S. G.Lathia J. D.Warren P. M.Silver D. J.Silver J.
2023
J Neurotrauma. 2023 Dec;40(23-24):2500-2521. doi: 10.1089/neu.2023.0117. Epub 2023 Oct 11.
Centre for Reconstructive NeuroscienceCarnicer-Lombarte A.Barone D. G.Wronowski F.Malliaras G. G.Fawcett J.Franze K.
2023
Biomaterials . 2023 Dec:303:122393. doi: 10.1016/j.biomaterials.2023.122393. Epub 2023 Nov 9.
Centre for Reconstructive NeuroscienceMizumoto S.Kwok J. C. F.Whitelock J.M.Li F.Perris, R.
2022
Frontiers in Cell and Developmental Biology. 10: 941178.
Centre for Reconstructive NeuroscienceBarone D.G.Carnicer-Lombarte A.Tourlomousis P.Hamilton R.S.Prater M.Rutz A.L.Dimov I.B.Malliaras G.G.Lacour S.P.Robertson A.A.B.Franze K.Fawcett J.Bryant C.E.
2022
National Academy of Sciences of the United States of America. 119(12): e2115857119
Centre for Reconstructive NeuroscienceYang S.Gigout S.Molinaro A.Naito-Matsui Y.Hilton S.Foscarin S.Nieuwenhuis B.Tan Ch.L.Verhaagen J.Pizzorusso T.Saksida L.M.Bussey T.M.Kitagawa H.Kwok J. C. F.Fawcett J.
2021
Molecular Psychiatry.
Centre for Reconstructive NeuroscienceNieuwenhuis B.Laperrousaz E.Tribble J. R.Verhaagen J.Fawcett J.Martin K. R.Williams P. A.Osborne A.
2023
Gene Ther. 2023 Jun;30(6):503-519. doi: 10.1038/s41434-022-00380-z. Epub 2023 Jan 13.
Centre for Reconstructive NeuroscienceSmith J. N.Doody N. E.Štěpánková K.Fuller M.Ichiyama R. M.Kwok J. C. F.Egginton S.
2023
Front Neuroanat . 2023 Mar 21:17:1152131. doi: 10.3389/fnana.2023.1152131. eCollection 2023.
Centre for Reconstructive NeuroscienceSrimasorn S.Souter L.Green D.E.Djerbal L.Goodenough A.Duncan J.A.Roberts A.R.E.Zhang X.Debarre D.DeAngelis P.L.Kwok J. C. F.Richter R.
2022
Scientific Reports. 12(1): 10980.
Centre for Reconstructive NeuroscienceEsteve D.Molina-Navarro M. M.Giraldo E.Varea N.Blanco-Gandia M.-C.Rodríguez-Arias M.García-Verdugo J. M.Viña J.Lloret A.
2022
Mol Neurobiol. 2022 Feb;59(2):1168-1182. doi: 10.1007/s12035-021-02620-6. Epub 2021 Dec 11.
Centre for Reconstructive NeuroscienceWarren P. M.Kissane R. W. P.Egginton S.Kwok J. C. F.Askew G. N.
2021
J Physiol . 2021 Feb;599(4):1199-1224. doi: 10.1113/JP280684. Epub 2020 Nov 22.
Centre for Reconstructive NeuroscienceDuncan J.A.Foster R.Kwok J. C. F.
2019
Br J Pharmacol. 2019 Sep;176(18):3611-3621. doi: 10.1111/bph.14672. Epub 2019 May 20.
2024
Nat Rev Neurosci . 2024 Oct;25(10):649-667. doi: 10.1038/s41583-024-00849-3. Epub 2024 Aug 20.
