Contributor:

Łukomska, Barbara (Promotor)

Publisher:

Instytut Medycyny Doswiadczalnej i Klinicznej im. M. Mossakowskiego PAN

Place of publishing:

Warszawa

Description:

Bibliogr. na str. 98-121 ; 121 s.: il., wykr., fotogr. ; 30 cm

Degree name:

doctor

Level of degree:

2

Degree discipline :

medical biology

Degree grantor:

Mossakowski Medical Research Center PAS

Abstract:

The aim of the study was to compare the immunomodulatory properties of human bone marrow mesenchymal stem cells (hBM-MSCs) and extracellular vesicles derived from these cells (EVs) transplanted in focal brain ischemic rats. Verification of therapeutic effects of MSCs or proposed EVs in experimental model of brain ischemia is necessary to begin clinical trials in patients. The studies were performed in adult male Wistar rats with focal brain injury of 1μl/50nmol ouabain injected into the right hemisphere. This cytotoxic brain injury model using ouabain (the inhibitor sodium-potassium pump) has been developed in our laboratory. Two days after ischemic insult 5x105 hBM-MSCs labeled with superparamagnetic iron oxide nanoparticles conjugated with rhodamine (Molday ION) or 1x109 EVs stained with PKH26 were transplanted into the right internal carotid artery of Wistar rats and the inflow of transplanted cells in the rat brain was monitored using MRI. At day 1, 3, 7 and 14 post-transplantation rats were decapitated, the brains were removed and the presence of the donor cells was confirmed by immunohistochemical studies. The cellular immune response in the brain was evaluated by immunohistochemical stainings and the production of humoral factors was measured by Bio-Plex ProTM Cytokine, Chemokine and Growth Factor Assay (BioRad). Our results showed that hBM-MSCs or EVs infused into the rat internal carotic artery migrated into the brain of graft recipients being visible in the right injured hemisphere using MRI or confocal microscope after immunohistochemical analysis up to 7 days after transplantation. The results revealed the decrease of activated microglia and leukocytes, including CD8+ T cells, evoked by ischemia in the brain tissue, after hBM-MSCs or EVs transplantation. The infusion of hBM-MSCs or EVs leaded to the reduction of cytokines: IL-1alfa, IL-1beta, IL-6, TGF-β2 and chemokines: CXCL1, MIP-1α, MIP-3α, MCP-1 in comparison to untreated rats with ischemic brain injury

Relation:

Prace doktorskie

Detailed Resource Type:

PhD Dissertations

Format:

pdf

Resource Identifier:

oai:rcin.org.pl:99855

Source:

IMDiK PAN, call no. ZS 388 ; click here to follow the link

Language:

pol

Language of abstract:

eng

Rights:

Creative Commons Attribution BY 4.0 license

Terms of use:

Copyright-protected material. [CC BY 4.0] May be used within the scope specified in Creative Commons Attribution BY 4.0 license, full text available at: ; -

Digitizing institution:

Mossakowski Medical Research Institute PAS

Original in:

Library of the Mossakowski Medical Research Institute PAS

Projects co-financed by:

Operational Program Digital Poland, 2014-2020, Measure 2.3: Digital accessibility and usefulness of public sector information; funds from the European Regional Development Fund and national co-financing from the state budget.

Access:

Open