Abstract Details

Title CX3CL1 Disruption Differentially Influences the Neuroprotective Effects of Mesenchymal Stromal Cells on ALS

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P4 - Poster Session 4 (5:30 PM-6:30 PM)

Poster/Presentation
Number 12-021

Objective We aimed to explore and validate the neuroprotective potential of mesenchymal stromal cells (MSC)treatment in amyotrophic lateral sclerosis(ALS), besides, we investigated whether the chemokine fractalkine (CX3CL1) was involved in the neuroprotective effect of MSC on ALS.

Background MSC represent a promising therapeutic candidate for clinical trials in ALS. CX3CL1 is constitutively expressed in the nervous system and has been shown to impact disease mechanisms in ALS. However, the role of CX3CL1 in the neuroptetective function of MSC on ALS, needs fto be further verified.

Design/Methods A mouse neuroblastoma cell (N2a) line stimulated by LPS and mutant SOD1G93A transgenic mice were used as in vitro and in vivo models in this study. Cell apoptosis in LPS-stimulated N2a cells with and without MSC treatment was assessed by cholecystokinin octapeptide(CCK-8) assay and flow cytometry. Differentially expressed genes under different conditions were investigated by western blot and real-time PCR. Cell viability and morphology changes were assessed via Nissl staining and immunofluorescence staining. Mutant SOD1G93A mice were treated by intrathecal injection of MSC or vehicle. Motor function of mice was tested through behavioral tests.

Results MSC significantly reduced expression of the cytokines tumor necrosis factor-??(TNF-??), IL-6 and CX3CL1 in vitro. Glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) were prominently enhanced upon MSC-treatment. Expression of CX3CL1 was decreased in mutant SOD1G93A trasgenic mice and LPS-stimulated N2a cells following MSC treatment. Overexpression of CX3CL1 in N2a cells, on the other hand, led to significant decline of neurotrophic factors and increase of chemokines as compared to MSC/N2a cells. However, only few non-significant changes were seen in CX3CL1 deficient cells.

Conclusions Taken together, our data suggest that MSC modulate neuronal and glial responses to inflammation. CX3CL1 was involved into the therapeutic effects of MSC on ALS and its overexpression endangered the protective function of MSC on ALS.

Authors/Disclosures
Dongya Huang, MD (East Hospital) PRESENTER	No disclosure on file
	No disclosure on file

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