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Stem Cell Rev. 2017 Apr;13(2):278-286. doi: 10.1007/s12015-016-9706-0.

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

Author information

1
Department of Ophthalmology, University Hospital, University of Bern, Freiburgstrasse 14, 3010, Bern, Switzerland. volker.enzmann@insel.ch.
2
Department of Clinical Research, University of Bern, Bern, Switzerland. volker.enzmann@insel.ch.
3
Department of Clinical Research, University of Bern, Bern, Switzerland.
4
NOXXON Pharma AG, Berlin, Germany.

Abstract

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.

KEYWORDS:

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

PMID:
27924617
DOI:
10.1007/s12015-016-9706-0
[Indexed for MEDLINE]

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