Pre-implantation factor promotes neuroprotection by modulating long non-coding RNA H19 of the neuronal stem cells

Spinelli, Marialuigia; Ornaghi, Sara; Schoeberlein, Andreina; Bordey, Angelique; Barnea, Eytan; Paidas, Michael; Surbek, Daniel; Müller, Martin (2018). Pre-implantation factor promotes neuroprotection by modulating long non-coding RNA H19 of the neuronal stem cells. Geburtshilfe und Frauenheilkunde, 78(10), p. 231. Thieme 10.1055/s-0038-1671458

Purpose: Successful therapies for periventricular leukomalacia (PVL) in premature infants are lacking. Post-injury activation of neural stem cells (NSCs) represents an attractive strategy and long non-coding RNA H19 is a candidate to regulate cell differentiation. Since synthetic-PreImplantation factor (sPIF) protects against neuronal disorders, we posit that sPIF activates NSCs after injury by modulating H19. Methods: A mouse model of PVL (n = 20) was electroporated with a pCAG-Cre plasmid (labelling NSCs). A H19-plasmid (pCMV-H19CA) was used to increase H19 activity in NSCs. Cell lines (Immature oligodendrocytes MO13.13) were treated with sPIF (200nM; 48h) or siRNA H19 and evaluated by qRT-PCR. Animals were evaluated by MRI, immunohistochemistry and in-situ hybridization. Significance was set at p < 0.05 *p < 0.05, **p < 0.01, ***p < 0.001. Results: In animals, both sPIF and H19CA ameliorated myelin loss significantly (Fig. 1A-B). In cell lines, sPIF increased mRNA expression of oligodendrocyte markers in H19-dependent manner (Fig. 1C). sPIF also increased H19 expression in the brain (Fig. 1D). Conclusion: sPIF activates NSCs and prevents myelin loss by modulating H19. Given the FDA Fast Track designation and safety data of sPIF in First in Human Trial (NCT02239562), clinical trials to prevent or treat PVL can be envisioned.

Item Type:

Conference or Workshop Item (Poster)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Pränatale Medizin

UniBE Contributor:

Spinelli, Marialuigia; Schoeberlein, Andreina; Surbek, Daniel and Müller, Martin

Subjects:

500 Science
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0016-5751

Publisher:

Thieme

Language:

English

Submitter:

Andreina Schoeberlein

Date Deposited:

02 Oct 2019 15:12

Last Modified:

02 Oct 2019 15:12

Publisher DOI:

10.1055/s-0038-1671458

URI:

https://boris.unibe.ch/id/eprint/129485

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