CXCL12/SDF-1-Dependent Retinal Migration of Endogenous Bone Marrow-Derived Stem Cells Improves Visual Function after Pharmacologically Induced Retinal Degeneration.

Enzmann, Volker; Lecaudé, Stéphanie; Kruschinski, Anna; Vater, Axel (2017). CXCL12/SDF-1-Dependent Retinal Migration of Endogenous Bone Marrow-Derived Stem Cells Improves Visual Function after Pharmacologically Induced Retinal Degeneration. Stem cell reviews and reports, 13(2), pp. 278-286. Springer 10.1007/s12015-016-9706-0

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Mobilized bone marrow-derived stem cells (BMSC) have been discussed as an alternative strategy for endogenous repair. Thereby, different approaches for BMSC mobilization have been pursued. Herein, the role of a newly discovered oligonucleotide for retinal homing and regeneration capability of BMSCs was investigated in the sodium iodate (NaIO3) model of retinal degeneration. Mobilization was achieved in GFP-chimera with NOX-A12, a CXC-motif chemokine ligand 12 (CXCL12)/stromal cell-derived factor 1 (SDF-1)-neutralizing L-aptamer. BMSC homing was directed by intravitreal SDF-1 injection. Visual acuity was measured using the optokinetic reflex. Paraffin cross sections were stained with hematoxylin and eosin for retinal thickness measurements. Immunohistochemistry was performed to investigate the expression of cell-specific markers after mobilization. A single dose of NOX-A12 induced significant mobilization of GFP(+) cells which were found in all layers within the degenerating retina. An additional intravitreal injection of SDF-1 increased migration towards the site of injury. Thereby, the number of BMSCs (Sca-1(+)) found in the damaged retina increased whereas a decrease of activated microglia (Iba-1(+)) was found. The mobilization led to significantly increased visual acuity. However, no significant changes in retinal thickness or differentiation towards retinal cell types were detected. Systemic mobilization by a single dose of NOX-A12 showed increased homing of BMSCs into the degenerated retina, which was associated with improved visual function when injection of SDF-1 was additionally performed. The redistribution of the cells to the site of injury combined with their observed beneficial effects support the endogenous therapeutic strategy for retinal repair.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Augenklinik > Forschungsgruppe Augenheilkunde
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)

UniBE Contributor:

Enzmann, Volker and Lecaudé, Stéphanie

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1550-8943

Publisher:

Springer

Language:

English

Submitter:

Volker Enzmann

Date Deposited:

29 May 2017 08:45

Last Modified:

07 Dec 2017 02:30

Publisher DOI:

10.1007/s12015-016-9706-0

PubMed ID:

27924617

Uncontrolled Keywords:

Bone marrow-derived stem cells (BMSC); L-aptamer; Mobilization; NOX-A12; Olaptesed pegol; Retinal degeneration; Sodium iodate; Spiegelmer

BORIS DOI:

10.7892/boris.96261

URI:

https://boris.unibe.ch/id/eprint/96261

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