Institute of Experimental Medicine CAS

The main topics studied in the Department are isolation, labelling and the use of stem cells for the treatment of brain injury, spinal cord and neurodegenerative diseases. Various types of cells (mesenchymal stem cells, neural precursor cell lines derived from fetal spinal cord, or from induced pluripotent cells) are studied, together with anti-inflammatory substances for their potential to promote the regeneration of nervous tissue. Macroporous polymeric hydrogels are used as suitable carriers for cell growth in in vitro cultures as well as for in vivo implantations facilitating the regeneration of the injured tissue. The aim of the cell therapy is to repair, replace or improve biological functions of the damaged neural tissue. For in vivo imaging of grafted cells and drug delivery we utilize magnetic nanoparticles, which are characterized in terms of cytotoxicity and genotoxicity and their influence on grafted cells and host tissue.

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Deputy Head:

Lucia Urdzíková-Machová, MD, PhD.
E-mail: lucia.machova@iem.cas.cz
Tel.: +420 241 062 619

Research Scientists:

Slaven Erceg, PhD.
Assoc. Prof. Aleš Hejčl, MD, PhD.
Assoc. Prof. Pavla Jendelová, PhD.
Kristýna Kárová, PhD.
Petr Krůpa, MD, PhD.
Dana Mareková, PhD.
Yuriy Petrenko, PhD.
Olena Rohulska, PhD.
Nataliya Romanyuk, PhD.
Jiří Růžička, PhD.
Karolína Turnovcová, MD, PhD.
Lucia Urdzíková-Machová, MD, PhD.

PhD. Students:

Ivan Arzhanov, MSc
Kateřina Havelíková, MSc
Jarmila Havelková, MSc
Barbora Smejkalová, MSc
Kristýna Šintáková, MSc
Kateřina Štěpánková, MSc
Ingrid Vargová, MSc
Eliška Vavřinová

Pre-Grad Students:

Tereza Klausová
Zuzana Polčanová
Tereza Špundová

Technicans:

Zuzana Čermáková
Michal Douděra
Lenka Kohoutová
Karel Třešňák
Hana Vargošková

Important result in 2021

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.

2021-analyza-lc3b

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.

 

 

 

Important result in 2020

Ventral lesion - new experimental model of spinal cord

There is currently no suitable experimental model of ventral spinal cord injury, which is relatively common in humans. Ventral spinal cord compression was induced by epidural insertion of a 2F Fogarty catheter balloon at the level of the thoracic spinal cord. The balloon was quickly inflated with 10 or 15 μl of saline and left in place for 5 minutes. The size of the lesion correlates well with the volume of the catheter balloon. Compression of 15 μL led to severe motor and sensory damage, loss of motoneurons, and increased astrogliosis.

2020-ventralni-leze

Micro computed tomography (CT) images of ventral epidural catheter placement

In order to evaluate the position of the catheter (red arrows) in front of the spinal cord, micro CT with bone window (A,C) and soft tissue window (B) were applied. Furthermore, detailed images of the deflated balloon (D), as well as inflated to 10 µL (E) and 15 µL (F) volume balloon were obtained. Black arrows show the wire of the catheter, whereas white arrows point to the imaged saline solution indicating the amount of inflated Fogarty´s balloon. Scale bar: 2 mm.

 

 

Important result in 2019

The effect of hMSCs on cell death pathways in the spinal cord of ALS rats

An increasing number of studies have demonstrated the beneficial effects of human mesenchymal stem cells (hMSC) in the treatment of amyotrophic lateral sclerosis (ALS). We compared the effect of repeated intrathecal applications of hMSCor their conditioned medium (CondM) using lumbar puncture or injection into the muscle ( quadriceps femoris), or a combination of both applications in symptomatic SOD1G93A rats. We further assessed the effect of the treatment on 3 major cell death pathways (necroptosis, apoptosis and autophagy) in the spinal cord tissue.

All symptomatic SOD1 rats treated with hMSC had a significantly increased lifespan, improved motor activity and reduced number of TUNEL positive cells. Moreover, a combined hMSC delivery increased motor neuron survival, maintained neuromuscular junctions in quadriceps femoris and substantially reduced the levels of proteins involved in necroptosis (Rip1, MLKL,cl-casp8), apoptosis (cl-casp 9) and autophagy (beclin 1). Furthermore, astrogliosis and elevated levels of Connexin 43 were decreased after combined hMSC treatment. The repeated application of CondM, or intramuscular injections alone, improved motor activity however, this improvement was not supported by changes at the molecular level. Our results provide new evidence that a combination of repeated intrathecal and intramuscular hMSC applications protects motor neurons and neuromuscular junctions, not only through a reduction of apoptosis and autophagy but also through the necroptosis pathway, which is significantly involved in cell death in rodent SOD1G93A model of ALS.

Repeated application of stem cells (hMSC) into spinal cord and muscles increased lifespan of the ALS rats, reduced expression of apoptotic protein cleaved caspase 9, necroptotic protein MLKL and beclin involved in autophagy (C). As a result we observed rescued motoneurons (D) and neuromuscular junctions (E) in cell treated ALS rats.

2021

Tichotová, L., Studenovska, H., Petrovski, G., Popelka, Š., Nemesh, Y., Sedláčková, M., Drutovič, S., Rohiwal, S., Jendelová, P., Erceg, S., Brymová, A., Artero-Castro, A., Lytvynchuk, L., Straňák, Z., Ellederová, Z., Motlik, J., Ardan, T.: (2021) Advantages of nanofibrous membranes for culturing of primary RPE cells compared to commercial scaffolds. Acta Ophthalmologica. https://doi.org/10.1111/aos.15034

Horák, D., Turnovcová, K., Plichta, Z., Mareková, D., Proks, V., Kaiser, R., Netuka, D., Jendelová, P.: (2021) RGDS- and doxorubicin-modified poly[N-(2-hydroxypropyl) methacrylamide]-coated gamma-Fe2O3 nanoparticles for treatment of glioblastoma. Colloid and Polymer Science. https://doi.org/10.1007/s00396-021-04895-6

Štepánková, K., Jendelová, P., Machová Urdziková, L.: (2021) Planet of the AAVs: The Spinal Cord Injury Episode. Biomedicines. 9(6): 613.

Vargová, I., Machová Urdziková, L., Kárová, 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.

Turnovcová, K., Mareková, D., Sursal, T., Krupová, M., Gandhi, R., Krupa, P., Kaiser, R., Herynek, V., Netuka, D., Jendelová, P.: (2021) Understanding the Biological Basis of Glioblastoma Patient-derived Spheroids. Anticancer Research. 41(3): 1183-1195.

Artero-Castro, A., Long, K., Bassett, A., Avila-Fernandez, A., Cortón, M., Vidal-Puig, A., Jendelová, P., Rodriguez-Jimenez, F.J., Clemente, E., Ayuso, C, Erceg, S.: (2021) Gene Correction Recovers Phagocytosis in Retinal Pigment Epithelium Derived from Retinitis Pigmentosa-Human-Induced Pluripotent Stem Cells. International Journal of Molecular Sciences.22(4): 2092.

Krátká, M., Čermák, J., Vachelová, J., Davídková, M., Romanyuk, N., Kromka, A., Rezek, B.: (2021) Gamma radiation effects on diamond field-effect biosensors with fibroblasts and extracellular matrix. Colloids and Surfaces B-Biointerfaces. 204: 111689.

Rogulska, O.Y., Trufanova, N.A., Petrenko, Y.A., Repin, N.V., Grischuk, V.P., Ashukina, N.O., Bondarenko, S.Y., Ivanov, G.V., Podorozhko, E.A., Lozinsky, V.: (2021) Generation of bone grafts using cryopreserved mesenchymal stromal cells and macroporous collagen-nanohydroxyapatite cryogels. Journal of Biomedical Materials Research. Part B.

Krupa, P., Kanta, M., Hosszu, T., Soukup, J., Ryska, P., Dulicek, P., Cesak, T.: (2021) A rare case of non-traumatic spinal epidural hematoma in lumbar region associated with apixaban therapy. Journal of Thrombosis and Thrombolysis. 52(4): 1215-1219.

Nordahl, E.R., Uthamaraj, S., Dennis, K.D., Sejkorova, A., Hejčl, A., Hron, J., Svihlova, H., Carlson, K.D., Suzen, Y.B., Dragomir-Daescu, D.: (2021) Morphological and Hemodynamic Changes during Cerebral Aneurysm Growth. Brain Sciences.11(4): 520 SI.

Klionsky DJ… Jendelova P, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) Autophagy. 2021 Jan;17(1):1-382. doi: 10.1080/15548627.2020.1797280.

Keša, P.; Paúrová, M.; Babič, M.; Heizer, T.; Matouš, P.; Turnovcová, K.; Mareková, D.; Šefc, L.; Herynek, V. Photoacoustic Properties of Polypyrrole Nanoparticles. Nanomaterials 2021, 11, 2457. https://doi.org/10.3390/nano11092457

 

2020

Krůpa, P., Stěpánková, K., Kwok, J.C.F., Fawcett, J.W., Cimermanová, V., Jendelová, P., Machová Urdzíková, L.: (2020) New Model of Ventral Spinal Cord Lesion Induced by Balloon Compression in Rats. Biomedicines. 8(11): E477.

Artero-Castro, A., Rodriguez-Jiménez, F.J.,  Jendelová, P., VanderWall, K.B., Meyer, J.S., Erceg, S.: (2020) Glaucoma as a Neurodegenerative Disease Caused by Intrinsic Vulnerability Factors. Progress in Neurobiology. 193: 101817

Mareková, D., Turnovcová, K., Sursal, T.H., Gandhi, C.D., Jendelová, P., Jhanwar-Uniyal, M.: (2020) Potential for treatment of glioblastoma: New aspects of superparamagnetic iron oxide nanoparticles. Anticancer Research. 40(11): 5989-5994.

Petrenko, Y., Vacková, I., Kekulová, K., Chudíčková, M., Koči, Z., Turnovcová, K., Skalníková-Kupcová, H., Vodička, P., Kubinová, Š.: (2020) A Comparative Analysis of Multipotent Mesenchymal Stromal Cells derived from Different Sources, with a Focus on Neuroregenerative Potential. Scientific Reports. 10(1): 4290.

Rodriguez-Jimenez, F.J., Vilches, A., Perez-Arago, M.A., Clemente, E., Roman, R., Leal, J., Castro, A.A., Fustero, S., Moreno-Manzano, V.,  Jendelová, P., Stojkovic, M., Erceg, S.: (2020) Activation of Neurogenesis in Multipotent Stem Cells Cultured in Vitro and in the Spinal Cord Tissue After Severe Injury by Inhibition of Glycogen Synthase Kinase-3. Neurotherapeutics. IN PRESS

Forostyak S, Forostyak O, Kwok JCF, Romanyuk N, Rehorova M, Kriska J, Dayanithi G, Raha-Chowdhury R, Jendelova P, Anderova M, Fawcett JW, Sykova E.: Transplantation of Neural Precursors Derived from Induced Pluripotent Cells Preserve Perineuronal Nets and Stimulate Neural Plasticity in ALS Rats. Int J Mol Sci. 2020 Dec 16;21(24):9593.

 

2019

Androvic, P., Romanyuk, N., Urdziková-Machová, L., Rohlová, E,., Kubista, M., Valihrach, L.: (2019) Two-tailed RT-qPCR panel for quality control of circulating microRNA studies.  Scientific Reports. 9: 4255.

Artero Castro, A., Machuca, C., Rodriguez Jimenez, F.J., Jendelová, P., Erceg, S.: (2019) Short Review: Investigating ARSACS: models for understanding cerebellar degeneration. Neuropathology and Applied Neurobiology.45(6): 531-537.

Artero Castro, A., Rodríguez Jimenez, F.J., Jendelová, P., Erceg, S.: (2019) Deciphering Retinal Diseases through the Generation of Three Dimensional Stem Cell-derived Organoids. Stem Cells.

Artero-Castro, A., Popelka, Š., Jendelová, P., Motlík, J., Ardan, T., Jimenez, F.J.R., Erceg, S.: (2019)  The identification of small molecules that stimulate retinal pigment epithelial cells: potential novel therapeutic options for treating retinopathies. Expert Opinion on Drug Discovery. 14 (2): 169-177.

Herynek, V., Turnovcová, K., Galisová, A., Kaman, O., Mareková, D., Koktan, J., Vosmanská, M., Kosinoá, L., Jendelová, P.: (2019) Manganese-Zinc Ferrites: Safe and Efficient Nanolabels for Cell Imaging and Tracking In Vivo. ChemistryOpen. 8(2): 155-165.

Horák, D., Plichta, Z., Mareková, D., Turnovcová, K., Kaiser, R., Jendelová, P.: (2019) Poly[N‐(2‐hydroxypropyl)methacrylamide]‐modified magnetic γ‐F2O3 nanoparticles conjugated with doxorubicin for glioblastoma treatment. ChemMedChem.

Chudíčková, M., Vacková, I., Machová Urdzíková L., Jancová, P., Kekulová, K., Řehořová, M., Turnovcová, K., Jendelová, P., Kubinová, S.: (2019) The Effect of Wharton Jelly-Derived Mesenchymal Stromal Cells and Their Conditioned Media in the Treatment of a Rat Spinal Cord Injury. International Journal of Molecular Sciences. 20: 4516.

Jirák, D., Ziolkowska, N., Turnovcová, K., Kárová, K., Syková, E., Jendelová, P., Romanyuk, N.: (2019) Metabolic Changes in Focal Brain Ischemia in Rats Treated With Human Induced Pluripotent Stem Cell-Derived Neural Precursors Confirm the Beneficial Effect of Transplanted Cells. Frontiers in Neurology.10:1074.

Jiráková, K., Moskvin, M., Machová Urdzíková, L., Rössner, P., Elzeinová, F., Chudíčková, M., Jirák, D., Ziolkowská, N., Horák, D., Kubinová, Š., Jendelová, P.: (2019) The negative effect of magnetic nanoparticles with ascorbic acid on peritoneal macrophages. Neurochemical Research.

Krůpa, P., Svobodová, B., Dubišová, J., Kubinová, Š., Jendelová, P., Machová Urdzíková, L.: (2019) Nano-formulated curcumin (Lipodisq (TM)) modulates the local inflammatory response, reduces glial scar and preserves the white matter after spinal cord injury in rats. Neuropharmacology. 155: 54-64.

Machuca, C., Vilches, A., Clemente, E., Pascual-Pascual, S.I., Bolinches-Amoros, A., Castro, A.A., Espinos, C., Leon, M., Jendelová, P., Erceg, S.: (2018) Generation of human induced pluripotent stem cell (iPSC) line from an unaffected female carrier of mutation in SACSIN gene. Stem Cell Research. 33: 166-170.

Neumannová, K., Machová-Urdzíková, L., Kwok, J.C.F., Fawcett, J.W., Jendelová, P.: (2019) Adaptation of tape removal test for measurement of sensitivity in perineal area of rat. Experimental Neurology.

Opattová A., Horák, J., Vodenková, S., Kostovciková K., Čumová, A., Macinga,P., Galanová, N., Rejhová, A., Vodičková, L., Kozics, K., Turnovcová, K., Hucl, T., Slíva, D., Vodička, P.: (2019) Ganoderma Lucidum induces oxidative DNA damage and enhances the effect of 5-Fluorouracil in colorectal cancer in vitro and in vivo. Mutation Research - Genetic Toxicology and Environmental Mutagenesis. 845: 403065.

Petrenko, Y., Chudíčková, M., Vacková, I., Groh, T., Košnarová, E., Čejková, J., Turnovcová, K., Petrenko, A., Syková, E., Kubinová, Š.: (2019) Clinically Relevant Solution for the Hypothermic Storage and Transportation of Human Multipotent Mesenchymal Stromal Cells. Stem Cells International. 2019: 590952.

Růžička, J., Romanyuk, N., Jiráková, K., Hejčl, A., Janoušková, O., Machová Urdziková, L., Bochin, M., Přádný, M., Vargová, L., Jendelová, P.: (2019) The Effect of iPS-Derived Neural Progenitors Seeded on Laminin-Coated pHEMA-MOETACl Hydrogel with Dual Porosity in a Rat Model of Chronic Spinal Cord Injury. Cell Transplantation. 28 (4): 400-412.

Růžička, J., Urdziková Machová, L., Kloudová, A., Amin, A.G., Vallová, J., Kubinová, Š., Schmidt, M.H., Jhanwar-Uniyal, M., Jendelová, P.: (2018) Anti-inflammatory compound curcumin and mesenchymal stem cells in the treatment of spinal cord injury in rats. Acta Neurobiologiae Experimentalis. 78(4): 358-374.

Řehořová, M., Vargová, I., Forostyak, S., Vacková, I., Turnovcová, K., Kupcová Skalníková, H., Vodička, P., Kubinová, S., Syková, E., Jendelová, P.: (2019) A Combination of Intrathecal and Intramuscular Application of Human Mesenchymal Stem Cells Partly Reduces the Activation of Necroptosis in the Spinal Cord of SOD1(G93A) Rats. Stem Cells Translational Medicine. 8 (6): 535-547.

Svobodová, B., Kloudová, A., Růžička, J., Kajtmanová, L., Navrátil, L., Sedláček, R., Suchý, T., Jhanwar-Uniyal, M., Jendelová, P., Machová Urdziková, L.: (2019) The effect of 808 nm and 905 nm wavelength light on recovery after spinal cord injury. Scientific Reports. 9: 7660.

Výborný, K., Vallová, J., Kočí, Z., Kekulová, Jiráková, K., Jendelová, P., Hodan, J., Kubinová, Š.: (2019) Genipin and EDC crosslinking of extracellular matrix hydrogel derived from human umbilical cord for neural tissue repair.  Scientific Reports. 9: 10674.

Skalnikova HK, Bohuslavova B, Turnovcova K, Juhasova J, Juhas S, Rodinova M, Vodicka P.: Isolation and Characterization of Small Extracellular Vesicles from Porcine Blood Plasma, Cerebrospinal Fluid, and Seminal Plasma. Proteomes. 2019 Apr 25;7(2). pii: E17. doi: 10.3390/proteomes7020017. PubMed PMID: 31027284; PubMed Central PMCID: PMC6630935.

Petrenko Y, Chudickova M, Vackova I, Groh T, Kosnarova E, Cejkova J, Turnovcova K, Petrenko A, Sykova E, Kubinova S.: Clinically Relevant Solution for the Hypothermic Storage and Transportation of Human Multipotent Mesenchymal
Stromal Cells. Stem Cells Int. 2019 Jan 20;2019:5909524. doi: 10.1155/2019/5909524. eCollection 2019. PubMed PMID: 30805009; PubMed Central PMCID: PMC6360551.

Center of Reconstruction Neuroscience – NEURORECON CZ.02.1.01/0.0/0.0/15_003/0000419 Coordinator Pavla Jendelova 2017–2022

GA ČR 21-04420S Protective coatings against dissolution/disintegration of upconverting lanthanide-based nanoparticles in biological media
Co.Principal Investigator Lucia Machová Urdzíková MD, PhD, 2021-2023

GA ČR 22-12483S Polymer-based drug delivery vectors targeting stemness and metabolism of glioblastoma cells
Principal Investigator Assoc Prof Pavla Jendelová, PhD, 2022-2024

GA ČR 22-31457S Metabolic reprogramming of mesenchymal stromal cells for regenerative medicine applications
Principal Investigator Yuriy Petrenko, PhD, 2022-2024

AZV NU21-08-00286 Monitoring of serum biomarkers in patients with acute spinal cord injury
Principal Investigator Nataliya Romanyuk, PhD, 2021-2024

AZV NU22-08-00124 Blood flow modelling in intracranial vessels in relationship to endothelium changes and development of intracranial aneurysms
Principal Investigator Lucia Machová Urdzíková MD, PhD, 2022-2025

GAUK 320421 Axon regeneration induced by blocking inhibitors produced by glial cells combined with expression of activated integrin 
Principal Investigator Kateřina Štěpánková, MSc, 2021-2023

GAUK 390722 The effect of 3D microenvironment on paracrine activity of multipotent mesenchymal stromal cells
Principal Investigator Eliška Vavřinová, 2022-2024

GAUK 409222 The role of sEVs derived from stem cell culture medium in the regeneration of spinal cord injury in vitro
Principal Investigator Kristýna Šintáková, MSc, 2022-2024

GAUK 102122 Regeneration of sensory axons after spinal cord injury
Principal Investigator Barbora Smejkalová, MSc, 2022-2024

Institute for Clinical and Experimental Medicine

Institute of Macromolecular Chemistry CAS

Physical Institute CAS

2nd Faculty of Medicine, Charles University

Faculty of Medicine Hradec Králové, Charles University

Faculty of Biomedical Engineering, Czech Technical University

Faculty of Mechanical Engineering, Czech Technical University

Cambridge University, UK

University of Leeds, UK

Centro de Investigación Príncipe Felipe, Valencia, Spain

New York Medical College, Valhalla, USA

IQS Group

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