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

• Published in: Stem cell reviews and reports 2017-04, Vol.13 (2), p.278-286
• Main Authors: Enzmann, Volker, Lecaudé, Stéphanie, Kruschinski, Anna, Vater, Axel
• Format: Article
• Language: English
• Subjects: Animals; Aptamers, Nucleotide; Bone Marrow Cells - cytology; Bone Marrow Cells - metabolism; Cell Movement - drug effects; Chemokine CXCL12 - administration & dosage; Chemokine CXCL12 - pharmacology; Glial Fibrillary Acidic Protein - metabolism; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Immunohistochemistry; Injections, Intraocular; Iodates; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - metabolism; Mice, Inbred C57BL; Mice, Transgenic; Retina - cytology; Retinal Degeneration - chemically induced; Retinal Degeneration - physiopathology; Retinal Degeneration - prevention & control; Tubulin - metabolism; Visual Acuity - drug effects
• ISSN: 2629-3269; 2629-3277
• DOI: 10.1007/s12015-016-9706-0

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 (NaIO ) 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.