Institute of Experimental Medicine CAS

Research of this Department is focused on the isolation, characterization and cultivation of stem cells and their use for treatment of severe injuries or so far uncurable diseases. Stem cells are propagated in tissue cultures and using various nanofiber scaffolds transferred onto mechanically or chemically damaged ocular surface. The ability of transferred cells to inhibit a harmful inflammatory immune reaction ocurring in the site of injury and to support healing process is evaluated. The ultimate goal of the research is to get insights into the mechanisms of specific immune response after transplantation of stem cells with the aim to increase their antiinflammatory and therapeutic potential. The experience with the study of transplantation immunity and the combination of nanotechnologies with stem cell research enable to propose and test novel therapeutic approaches. The recent study is extended on the development of stem cell-based therapy for currently uncurable serious sight-threatening retinal diseases.

Deputy Head:

Eliška Javorková, PhD.
E-mail: javorkova@biomed.cas.cz
Phone: +420 241 063 108

Research Scientists:

Michaela Hájková , PhD.
Prof. Vladimír Holáň, DrSc.
Eliška Javorková, PhD.
Magdaléna Krulová, PhD.
Alena Zajícová, PhD.

PhD. Students:

Pavla Boháčová, MSc
Barbora Heřmánková, MSc
Jan Kössl, MSc

Undergraduate Students:

Kateřina Palacká
Bianka Porubská

Technicans:

Lucie Holáňová
Jaroslava Knížová

Important result in 2017

Mesenchymal stem cells have been proved as a promising tool for cell-based therapy of currently uncurable degenerative diseases of the retina

Degenerative diseases of the retina represent the most common cause of decreased quality of vision or even blindness. So far, there is no treatment protocols for these disorders. We showed that mesenchymal stem cells can be differentiated into cells expressing markers of the retinal cells, possess potent immunoregulatory properties and produce numerous neuroprotective and growth factors. These properties make them a prospective cell type for the treatment of degenerative retinal disorders.

  Diferenciace mesenchymálních kmenových buněk v buňky exprimující znaky sítnice

Differentiation of mesenchymal stem cells into cells expressing retinal markers. Mouse mesenchymal stem cells were cultured untreated (-), with supernatant from stimulated T cells (Sup),  with retinal extract (Ext) or  with supernatant and extract together (Sup + Ext). The expression of retinal markers Rho, Sag, Rcvr, Rlbp, Rpe65 and Calb2 was detected after 7-day cultivation by RT-PCR.

Publication: Heřmánková B., Kössl J., Javorková E., Boháčová P., Hájková M., Zajícová A., Krulová M., Holáň V.: The identification of interferon-gama as a supportive factor for retinal differentiation of murine mesenchymal stem cells. Stem cells Dev. 26, 1399-1408, 2017. IF 3.562
Holáň V. Heřmánková B., Kössl J.: Perspectives of stem cell-based therapy for age-related retinal degenerative diseases. Cell Transplant. 26, 138-141, 2017. IF 3.006

 

Important result in 2016

The effects of cytokines on immunomodulatory properties of mesenchymal stem cells

Immunoregulatory and therapeutic properties of mesenchymal stem cells (MSCs) can be modified by cytokines. We described that the production of immunoregulatory molecules by MSCs depends on their activation and that their secretory profile significantly modulates immunological reactions. A novel mechanism used by MSCs to inhibit production of interleukin-10 by activated B cells was characterized. Thus, MSCs can regulate harmful inflammatory reactions in dependence on the cytokine environment.

  holan-2016-1-en

Immunoregulatory properties of mesechymal stem cells. Mesenchymal stem cells (MSCs) regulate the reactivity of cells of specific immunity (Th- helper T cell, Tc – cytotoxic T cell, Treg – regulatory T cell, Breg – regulatory B cell) by multiple mechanisms in both positive and negative manner.

Publications:

  • Heřmánková B., Zajícová A., Javorková E., Chudíčková M., Trošan P., Hájková M., Krulová M., Holáň V.: Suppression of IL-10 production by activated B cells via a cell contact-dependent cyclooxygenase-2 pathway upregulated in IFN-gama-treated mesenchymal stem cells. Immunobiology, 221, 129-136, 2016. IF 2.720
  • Holáň V., Heřmánková B., Boháčová P., Kössl J., Chudíčková M., Hájková M., Krulová M., Zajícová A., Javorková E.: Distinct immunoregulatory mechanisms in mesenchymal stem cells: Role of the cytokine environment. Stem Cells Rev. Rep. 12, 654-663, 2016. IF 2.967

 Important result in 2015

Comparative study on the therapeutic potential of mesenchymal stem cells and tissue-specific limbal stem cells

The ability of mesenchymal stem cels (MSC) and limbal stem cells (LSC) to produce various immunoregulatory molecules and to modulate immune response was compared. The therapeutic potential of these stem cells was evaluated in the model of treatment of chemically damaged ocular surface in the rabbit. It was found that stem cells produce a number of immunoregulatory molecules and that MSC have comparable therapeutic properties as do tissue-specific LSC. These results bring the evidence that MSC can replace tissue-specific LSC in the cases when LSC are absent or difficult to obtain.

Charakterizace funkčních vlastností MSC

Characterization of MSC.  The ability of MSC to express genes for immunomodulatory molecules was determined by real-time PCR. The cells were cultured untreated or were stimulated with LPS, IFN-γ with LPS plus IFN-γ

2015holan2en

Therapeutic potential of MSC and LSC.  Stem cells were transferred using nanofiber scaffold onto damaged ocular surface and their therapeutic potential was evaluated. The figure shows healthy rabbit eye, the eye shortly after chemical damage, damaged eye covered with nanofiber scaffold, untreated damaged eye two weeks after the injury and damaged eye treated with MSC or LSCC nebo LSC.

Publications: Holáň V., Trošan P., Čejka Č., Javorková E., Zajícová A., Heřmánková B., Chudíčková M, Čejková J.: A comparative study of the therapeutic potential of mesenchymal stem cells and limbal epithelial stem cells for ocular surface reconstruction. Stem Cells Translat. Med. 4, 1052-1063, 2015. IF 5.709.

GA ČR, 17-04800S - Stem cell-based therapy for serious degenerative retinal disorders, 2017-2019.

GA UK, 80815 - The therapeutic potential of mesenchymal stem cells in diabetic retinopathy, 2015-2017.

TAČR GAMA - Commercionalization of VaV results in IEM AS CR, 2015-2017.

MŠMT, NPU-I: LO1309 - Center of cell therapy and tissue regeneration, 2014-2019.

MŠMT, NPU-I: LO1508 - Center of genomic and proteomic, 2015-2020.

2018

Javorková, E. , Vacková, J., Hájková, M., Heřmánková, B., Zajícová, A., Holáň, V., Krulová, M.: (2018) The effect of clinically relevant doses of immunosuppressive drugs on human mesenchymal stem cells. Biomedicine & Pharmacotherapy. 97: 402-411.

2017

Heřmanková, B., Köss,l J., Javorková, E., Boháčová, P., Hájková, M., Zajicová, A., Krulová, M., Holáň, V.: (2017)  The identification of interferon-gamma as a key supportive factor for retinal differentiation of murine mesenchymal stem cells. Stem Cells and Development. 26(19): 1399-1408.

Holáň, V., Heřmánková, B., Kössl, J.: (2017)  Perspectives of stem cell-based therapy for age-related retinal degenerative diseases. Cell Transplantation. 26(9): 1538-1541.

Hájková, M., Heřmánková, B., Javorková, E., Boháčová, P., Zajícová, A., Holáň, V., Krulová, M.: (2017)  Mesenchymal stem cells attenuate the adverse effects of immunosuppressive drugs on distinct T cell subopulations. Stem Cell Reviews and Reports.13(1): 104-115.

Chudičková, M.  , Brůža, P., Zajícová, A., Trošan, P., Svobodová, L., Javorková, E., Kubinová, Š., Holáň, V.: (2017) Targeted neural differentiation of murine mesenchymal stem cells by a protocol simulating the inflammatory site of neural injury. Journal of Tissue Engineering and Regenerative Medicine. 11(5): 1588-1597.

Hájková, M., Javorková, E., Zajícová, A., Trošan, P., Holáň, V., Krulová, M.: (2017) A local application of mesenchymal stem cells and cyclosporine A attenuates immune response by a switch in macrophage phenotype. Journal of Tissue Engineering and Regenerative Medicine. 11(5): 1456-1465.

Čejka, Č., Kössl, J., Heřmánková, B., Holáň, V., Kubinová, Š., Zhang, J. H., Čejková, J.:  (2017) Therapeutic effect of molecular hydrogen in corneal UVB-induced oxidative stress and corneal photodamage. Scientific Reports. 7(1): 18017.

Čejka, Č., Kössl, J., Heřmánková, B., Holáň, V., Čejková, J.: (2017)  Molecular hydrogen effectively heals alkali-injured cornea via suppression of oxidative stress. Oxidative Medicine and Cellular Longevity. 8906027.

Širc, J., Hampejsová, Z., Trnovská, J., Kozlik, P., Hrib, J., Hobzová, R., Zajícová, A., Holáň, V., Bosaková, Z.: (2017) Cyclosporine A loaded electrospun poly(D,L-lactic acid)/poly(ethylene glycol) nanofibers: drug carriers utilizable in local immunosuppression. Pharmaceutical Research. 34(7): 1391-1401.

2016

Holáň, V., Heřmánková, B., Boháčová, P., Kössl, J., Chudičková, M., Hajková, M., Krulová, M., Zajícová, A., Javorková, E.: (2016)  Distinct immunoregulatory mechanisms in mesenchymal stem cells: Role of the cytokine environment. Stem Cell Reviews and Reports, 12(6): 654-663.

Heřmánková, B., Zajícová, A., Javorková, E., Chudíčková, M., Trošan, P., Hájková, M., Krulová, M., Holáň, V.: (2016)  Suppression of IL-10 production by activated B cells via a cell contact-dependent cyclooxygenase-2 pathway upregulated in IFN-γ-treated mesenchymal stem cells. Immunobiology, 221(2): 129-136.

Trošan, P., Javorková, E., Zajícová, A., Hájková, M., Heřmánková, B., Kössl, J., Krulová, M., Holáň, V.: (2016)  The supportive role of insulin-like growth factor-I in the differentiation of murine mesenchymal stem cells into corneal-like cells. Stem Cells and Development, 25(11): 874-881.

Čejka, Č., Čejková, J., Trošan, P., Zajícová, A., Syková, E., Holáň, V.: (2016)  Transfer of mesenchymal stem cells and cyclosporine A on alkali-injured rabbit cornea using nanofiber scaffolds strongly reduces corneal neovascularization and scar formation. Histology and  Histopathology, 31: 969-980.

Čejka, Č., Holáň, V., Trošan, P., Zajicová, A., Javorková E., Čejková, J.: (2016)  The favorable effect of mesenchymal stem cell treatment on the antioxidant protective mechanism in the corneal epithelium and renewal of corneal optical properties changed after alkali burns. Oxidative Medicine and Cellular Longevity. 5843809.

Čejková, J., Čejka, Č., Trošan, P., Zajícová, A., Syková, E., Holáň, V.: (2016)  Treatment of alkali-injured cornea by cyclosporine A-loaded electrospun nanofibers - An alternative mode of therapy. Experimental Eye Research, 147: 128-137.

Bílková, B., Albrecht, T., Chudičková, M., Holáň, V., Piálek, J., Vinkler, M.: (2016) Application of Concanavalin A during immune responsiveness skin-swelling tests facilitates measurement interpretation in mammalian ecology. Ecology and Evolution, 6 (13): 4551-4564.

Heřmánková, B., Holáň, V.: (2016) Perspektivy buněčné terapie v oftalmologii. 2, Potenciál kmenových buněk pro léčbu onemocnění sítnice. Česká a Slovenská Oftalmologie, 72: 272-275.

Javorková, E., Holáň, V.: (2016) Perspektivy buněčné terapie v oftalmologii. 1, Využití kmenových buněk v regeneraci poškozeného povrchu oka. Česká a Slovenská Oftalmologie, 72: 268-271.

2015

Holáň, V., Trošan, P., Čejka, Č., Javorková, E., Zajícová, A., Heřmánková, B., Chudíčková, M., Čejková, J.: (2015) A comparative study of the therapeutic potential of mesenchymal stem cells and limbal epithelial stem cells for ocular surface reconstruction. Stem Cells Translational Medicine. 4(9): 1052-1063.

Holáň, V., Heřmánková, B., Zajícová, A.: (2015) Nanofiber scaffolds for the growth and transfer of stem cells for the treatment of ocular surface damage. In: From Functionalized Nanostructures Towards Engineered Macrostructions, Eds. C. Caruana, J. Horník, Zittau, J. Hradec, 74-81.

Holáň, V., Boháčová, P., Kössl, J., Javorková, E.: (2015) Immunosuppressive drug-loaded nanofibers for the local inhibition of harmful inflammatory reactions. In: From Functionalized Nanostructures Towards Engineered Macrostructions, Eds. C. Caruana, J. Horník, Zittau, J. Hradec, 17-23.

Kubinova, Š., Zajícová, A., Holáň, V., Syková, E.: (2015) Nanofibers as scaffolds for cell transfer in tissue regeneration In: From Functionalized Nanostructures Towards Engineered Macrostructions, Eds. C. Caruana, J. Horník, Zittau, J. Hradec, 82-98.

Stříž, I., Holáň, V.: (2015) Cytokiny v klinické medicíně. Maxdorf Press, Prague.

Department of Cell Biology, Faculty of Science, Charles University in Prague
 
Department of Polymer Gels, Institute of Macromolecular Chemistry, CAS
 
Department of Biomedicine, Institute of Physiology, CAS

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