Poster Session I. - A: Molecular Medicine
Abdeldaeam Khloud, PhD
P8EF0T
Institute of Molecular Life Sciences, HUN-REN Research Center for Natural Sciences, Budapest, Hungary.
+36703644602
khloud.abdeldaeam@phd.semmelweis.hu
Unraveling the molecular basis of the interaction between microglia and human stem cell derived neural progenitor cells
Khloud Gamal Abdelsalam1,2, Márk Gere1, Krisztina Toth3, Ádám Denes3, Apáti Ágota1, László Homolya1
1: Institute of Molecular Life Sciences, HUN-REN Research Center for Natural Sciences, Budapest, Hungary.
2: Department of Molecular Biology, Semmelweis University, H-1085 Budapest, Hungary.
3: HUN-REN Institute of Experimental Medicine, Budapest, Hungary.
Poszter
Poster Session I. - A: Molecular Medicine
English
Molecular Medicine
Introduction:Neural progenitor cells (NPCs) play a pivotal role in neural development and tissue regeneration and thus hold great potential for stem cell-based therapeutic interventions for medical conditions affecting neural cells or tissues, such as neurodegenerative disease. The initial step of NPCs’ differentiation is the outgrowth of neurites, which is determined by a combination of internal and external factors. One of the external determinants is microglia, the brain-resident macrophage, which can have a profound effect on the inflammatory status of the affected area. Aim of the work:In the present work, we aim to better understand the molecular mechanism of how microglia influence neurite development of the human induced pluripotent stem cell (iPSC)-derived NPCs.
Method: We have previously demonstrated that BV2 cells stimulated either toward pro- or anti-inflammatory direction enhanced neurite outgrowth of human NPCs, and that pro-inflammatory microglia even promoted NPCs’ proliferation. Now we analyzed how microglia affected neurite numbers and their branching, as well as migratory properties of NPCs. To this end, we performed high content screening and analysis on GFP-expressing human iPSC-derived NPCs treated with the supernatants from BV2 cells pre-stimulated with pro- (IFN γ, LPS), or anti-inflammatory agents (IL 4, IL 13). In parallel, we explored the effect of pro- and anti-inflammatory stimulation on BV2 microglia morphology and motility. We also analyzed the major component of the cytokine secretome BV2 cells by a flow cytometry-based assay. Results:The most prominent observation from the cytokine analysis is the strong activation of BV2 cells by LPS, leading to massive cytokine release, in particular secretion of IL 6, TNF α, G CSF, CCL5, and CCL2. We also found that anti-inflammatory stimulation had only a minor effect on the secretion of the cytokines tested. Our further studies aim to identify the cytokines responsible for influencing motility and neurite formation of NPCs.Conclusion: The results from our study may help to elucidate the molecular details of the complex interactions between microglia and NPCs, which may contribute to optimizing the therapeutic use of stem cell-derived NPCs in the treatment of neurodegenerative and neurological injuries.
Funding: work supported by the Stipendium Hungaricum to KGA (grant number: K 128123).
Semmelweis University
László Homolya
I do not give consent to the publication of my abstract on the website of the congress.
in doctoral studies before complex exam (PhD)
Szabad
elfogadva
poszter
nem rendelkezett róla
8996
16:36
16:42