Department of Tissue Culture and Stem Cells

Department of Tissue Culture and Stem Cells

Department of Tissue Culture and Stem Cells

 

Head: Assoc. Prof. Pavla Jendelová, Ph.D.

E-mail: jendel@biomed.cas.cz
Tel.: +420 241 062 828

 
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.
 

Research Scientists:

Assoc. Prof. Pavla Jendelová, PhD.

Nataliya Romanyuk, PhD.

Lucia Urdzíková-Machová, MD, PhD.

Aleš Hejčl, MD, PhD.

Klára Jiráková, PhD.

Serhiy Forostyak, MD, PhD.

Karolína Turnovcová, MD, PhD.

Jiří Růžička, PhD

 

PhD Students:

Dana Mareková, MSc

Kristýna Kárová, MSc

Monika Šeneklová, MSc

Barbora Svobodová, MSc

Petr Krůpa, MD

Miroslava Kapcalová, MSc

 

Technicans:

Pavlína Macková

Michal Douděra

Important results in 2015



Mesenchymal stem cells reduce the working memory deficit in Alzheimer's disease model.
Stem cell transplantation may have a positive influence and slow the progression of some neurodegenerative diseases. In our study, we transplanted human mesenchymal stem cells (MSCs) into the lateral ventricle of 8 months old transgenic mice (AD-3xTg), which mimic the symptoms of Alzheimer's disease (AD). We studied the changes in the spatial reference and working memory, and the effect of transplanted MSCs on neurogenesis in the subventricular zone (SVZ). We also monitored the levels of harmful oligomer amyloid 56kDa (Ab*56), and the amount of the enzyme glutamine synthetase (GS), which is important for regulating the levels and metabolism of glutamate in the brain, in entorhinal and prefrontal cortex and in the hippocampus, i.e. in the structures that are related with cognitive functions. In 14 months old mice treated with MSC we observed preserved working memory, which may be a result of preserved levels of GS and significantly reduced levels of Ab*56 in the entorhinal cortex (Figure 1). These changes, observed six months after transplantation, were also accompanied by increased cell proliferation in the SVZ. Since the transplanted cells survive in the body of the recipient only for a limited period of time, it is likely that the observed effects could be even more pronounced in case of repeated administration of the stem cells at regular intervals during the life spam of the 3xTg mice.

 

Working memory test in mice with AD. The red line represents the second trial to find the island in the water maze. The ability to remember the position of the islet is shown at the top left of the chart. AD mice had in the entorhinal cortex reduced level of harmful amyloid oligomer Aβ*56. The graph on the bottom right. AD - Alzheimer's disease, EC - entorhinal cortex, ctrl - control animals were age-matched.

 

Publication:

Ruzicka J, Kulijewicz-Nawrot M, Rodrigez-Arellano JJ, Jendelova P, Sykova E. Mesenchymal Stem Cells Preserve Working Memory in the 3xTg-AD Mouse Model of Alzheimer's Disease. Int J Mol Sci. 2016 Jan 25;17(2)

Important results in 2014



1. Neural precursors from induced pluripotent cells (iPS-NP) significantly improve motor function in rats with spinal cord injury.
Grafted cells (iPS-NP) survived well and slowly mature into different neuronal phenotypes (GABAergic, Serotonergic and motoneurons). In addition, they produced growth factors, stimulating neuronal sprouting. As a result, animals with spinal cord injury significantly improved their motor function. Rats were able to support their body weight and perform stepping, so they scored well in tests requiring movement coordination, such as beam walking.

 

 
Rats implanted with neural precursors showed better functional outcome after spinal cord ijury and higher volume of spared white and grey matter. Grafted cells robustly survived in the lesion, migrated into the parenchyma and differentiated into gabaergic, dopaminergic and cholinergic neurons.

 

Collaboration: Brigitte Onteniente, INSERM
 
Publications:
Romanyuk N, Amemori T, Turnovcová K, Procházka P, Onteniente B, Syková E, Jendelová P, (2014): Beneficial effect of human induced pluripotent stem cell-derived neural precursors in spinal cord injury repair. Cell Transplant. [Epub ahead of print] IF 3.570.
 
 

2. Mesenchymal stem cells increase lifespan of animals with amyotrofic lateral sclerosis (ALS).
We studied the effect of human mesenchymal stem cells (MSCs) in the treatment of an experimental model of ALS. We found that application of MSCs improved motor performance and muscle strength and led to an extended lifespan. MSCs partially rescued motor neuron (MN) loss and decreased apoptosis. MSCs transplantation is therefore a safe procedure able to promote CNS remodeling and regeneration.

 
The effect of MSC application. After the appearance of fi rst disease symptoms SOD1 rats were treated (arrow) with MSCs (intrathecally, 5×105 cells/50μl) or vehicle-injected (DMEM, 50μl). Shortly after delivery of MSCs disease progression has been slowed down shown by the digger muscle strength (A) and higher motor activity (B). MSC-treated rats lived signifi cantly longer (C, D) and preserved higher number of ventral motor neurons (E) compared with vehicle-injected littermates. We found that SOD1 rats have deteriorated perineuronal nets structure around motor neurons and that application of MSCs partially preserved their structure (F).

 

Collaboration: Prof. James Fawcett, Cambridge, UK
 
Publication:
Forostyak S, Homola A, Turnovcová K, Svítil P, Jendelová P, Syková E, (2014): Intrathecal Delivery of Mesenchymal Stromal Cells Protects the Structure of Altered Perineuronal Nets in SOD1 Rats and Amends the Course of ALS. Stem Cells.;32(12):3163-72. IF 7.133


Important results in 2013



1. Treatment of spinal cord injury using stem cells and biomaterials.
The effect of Neural spinal progenitor cells and/or different types of synthetic hydrogels implanted into acute spinal cord lesion on functional outcome and tissue regeneration was evaluated. Stem cells differentiated into neurons, produced neurotrophins and improved functional outcome., while hydrogels bridged the lesion, facilitate axonal ingrowth into the implant and reduce glial scar formation.
 
 
Integration and differentiation of spinal progenitor cells in injured rat spinal cord. Two months after transplantation SPC-01 cells were positive for early transcription factors of interneurons and motor neurons NKX 1.6 and showed an increased expression of mature RNA characters, motorneurons Islet2 and HB9 (A). Four months after the transplantation of the graft, cells were positive for Islet2 and choline acetyl transferase (B) mature markers motoneurons.(Amemori et al., 2013).

 

Collaboration: King’s College London, Ústav makromolekulární chemie AV ČR
 
Publications:
Amemori, T., Romanyuk, N., Jendelová, P., Herynek, V., Turnovcová, K., Procházka, P., Kapcalová, M., Cocks, G., Price, J., Syková, E.: (2013) Human conditionally immortalized neural stem cells improve locomotor function after spinal cord injury in the rat. Stem Cell Res. Ther. 4(3): 68. IF 3,652
Cocks, G., Romanyuk, N., Amemori, T., Jendelová, P., Forostyak, O., Jeffries, A. R., Perfect, L., Thuretm S., Dayanithi, G., Syková, E., Price, J.: (2013) Conditionally immortalized stem cell lines from human spinal cord retain regional identity and generate functional V2a interneurons and motorneurons. Stem Cell Res. Ther. 4(3): 69. IF 3,652
Růžička, J., Romanyuk, N., Hejčl, A., Vetrik, M., Hrubý, M., Cocks, G., Cihlar, J., Přádný, M., Price, J., Syková, E., Jendelová, P.: (2013) Treating spinal cord injury in rats with a combination of human fetal neural stem cells and hydrogels modified with serotonin. Acta Neurobiol. Exp. 73(1): 102-115. IF 1,977.


2. Modification of polymeric hydrogels based on methacrylate, serving to bridge lesions and as carriers for cell therapy.
In cooperation with the Institute of Macromolecular Chemistry ASCR, we developed and tested polymer hydrogels based on methacrylate with different types of pores and surface modified positively charged peptides or RGD sequences. Hydrogels were implanted into a model of acute spinal cord hemisection. The results showed that the positive charge and network pore structure of the RGD sequences on the surface promotes cell growth, both in vitro and in vivo, as well as the ingrowth of axons and blood vessels of the host.
 

Methacrylate hydrogel with a modified surface bridged the spinal cord lesion (A) and promoted ingrowth of axons (B), blood vessels (C) and astrocytes (D). Served as a suitable carrier for transplanted stem cells.

 

Collaboration: Ústav makromolekulární chemie AV ČR
 
Publication:
Hejčl, A., Růžička, J., Kapcalová, M., Turnovcová, K., Krumbholcová, E., Přádný, M., Michálek, J., Cihlář, J., Jendelová, P., Syková, E.: (2013) Adjusting the chemical and physical properties of hydrogels leads to improved stem cell survival and tissue ingrowth in spinal cord injury reconstruction: a comparative study of 4 methacrylate hydrogels. Stem Cells Dev. 2013 Oct 15;22(20):2794-805. IF 4.670

Intrathecal and intramuscular application of mesenchymal stem cells and their secretome in the treatment of Amyotrophic lateral sclerosis GA ČR 15-06958S Principal Investigator Jendelová, 2015-2017

The treatment of chronic spinal cord injury using stem cells and enzymes in combination with polymer scaffolds GA ČR, 13-00939S. 2013-2016

Spinal cord injury reconstruction using surface-modified biodegradable hydrogels with oriented pores seeded with mesenchymal stem cells. GA ČR 14-14961S. 2014-2016

Biomaterials and stem cells in the treatment of stroke and SCI, MEYS – EEA Norwegian Research Council, 7F14057, 2014-2017

Institute for Clinical and Experimental Medicine

Institute of macromolecular chemistry ASCR

Physical Institute ASCR

2nd Faculty of Medicine, Charles University

Faculty of Medicine Hradec Králové, Charles University

Faculty of Biomedical Engineering, Czech Technical University