PMID- 27924617
OWN - NLM
STAT- MEDLINE
DCOM- 20171106
LR  - 20220331
IS  - 2629-3277 (Electronic)
IS  - 2629-3277 (Linking)
VI  - 13
IP  - 2
DP  - 2017 Apr
TI  - CXCL12/SDF-1-Dependent Retinal Migration of Endogenous Bone Marrow-Derived Stem 
      Cells Improves Visual Function after Pharmacologically Induced Retinal 
      Degeneration.
PG  - 278-286
LID - 10.1007/s12015-016-9706-0 [doi]
AB  - 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(3)) 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.
FAU - Enzmann, Volker
AU  - Enzmann V
AUID- ORCID: 0000-0003-4384-4855
AD  - Department of Ophthalmology, University Hospital, University of Bern, 
      Freiburgstrasse 14, 3010, Bern, Switzerland. volker.enzmann@insel.ch.
AD  - Department of Clinical Research, University of Bern, Bern, Switzerland. 
      volker.enzmann@insel.ch.
FAU - Lecaude, Stephanie
AU  - Lecaude S
AD  - Department of Clinical Research, University of Bern, Bern, Switzerland.
FAU - Kruschinski, Anna
AU  - Kruschinski A
AD  - NOXXON Pharma AG, Berlin, Germany.
FAU - Vater, Axel
AU  - Vater A
AD  - NOXXON Pharma AG, Berlin, Germany.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Stem Cell Rev Rep
JT  - Stem cell reviews and reports
JID - 101752767
RN  - 0 (Aptamers, Nucleotide)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Iodates)
RN  - 0 (NOX-A12)
RN  - 0 (Tubulin)
RN  - 0 (beta3 tubulin, mouse)
RN  - 0 (glial fibrillary astrocytic protein, mouse)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - U558PCS5Z9 (sodium iodate)
SB  - IM
MH  - Animals
MH  - Aptamers, Nucleotide
MH  - Bone Marrow Cells/cytology/metabolism
MH  - Cell Movement/*drug effects
MH  - Chemokine CXCL12/administration & dosage/*pharmacology
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Immunohistochemistry
MH  - Injections, Intraocular
MH  - Iodates
MH  - Mesenchymal Stem Cells/cytology/*drug effects/metabolism
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Retina/cytology
MH  - Retinal Degeneration/chemically induced/physiopathology/*prevention & control
MH  - Tubulin/metabolism
MH  - Visual Acuity/drug effects
OTO - NOTNLM
OT  - Bone marrow-derived stem cells (BMSC)
OT  - L-aptamer
OT  - Mobilization
OT  - NOX-A12
OT  - Olaptesed pegol
OT  - Retinal degeneration
OT  - Sodium iodate
OT  - Spiegelmer
EDAT- 2016/12/08 06:00
MHDA- 2017/11/07 06:00
CRDT- 2016/12/08 06:00
PHST- 2016/12/08 06:00 [pubmed]
PHST- 2017/11/07 06:00 [medline]
PHST- 2016/12/08 06:00 [entrez]
AID - 10.1007/s12015-016-9706-0 [pii]
AID - 10.1007/s12015-016-9706-0 [doi]
PST - ppublish
SO  - Stem Cell Rev Rep. 2017 Apr;13(2):278-286. doi: 10.1007/s12015-016-9706-0.