PMID- 24370836
OWN - NLM
STAT- MEDLINE
DCOM- 20140225
LR  - 20140130
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 55
IP  - 1
DP  - 2014 Jan 29
TI  - Effect of coadministration of neuronal growth factors on neuroglial 
      differentiation of bone marrow-derived stem cells in the ischemic retina.
PG  - 502-12
LID - 10.1167/iovs.13-12223 [doi]
AB  - PURPOSE: Brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor 
      (CNTF) have limited and transient supportive effects on retinal recovery from 
      ischemia. The aim of this study was to investigate their effect on engrafted 
      adult bone marrow-derived stem cells in a rodent model of anterior ischemic optic 
      neuropathy (rAION). METHODS: Small cells were isolated from the bone marrow of 
      green fluorescent protein expressing mice by counterflow centrifugal elutriation, 
      depleted of cells expressing lineage markers, and grafted in conjunction with 
      growth factors into the vitreous body of mice with unilateral rAION. Progenitors 
      were mobilized with granulocyte macrophage colony-stimulating factor (GM-CSF) or 
      stem cell factor (SCF). The contralateral eye served as a control. RESULTS: At 4 
      weeks, the quantitative incorporation of donor cells in the injured retina was 
      increased by BDNF (P < 0.01 versus control) and decreased by CNTF (P < 0.01 
      versus control), with no notable difference at 24 weeks. Both growth factors 
      improved the short-term and long-term qualitative engraftment of cells adopting 
      neural phenotypes in the retinal ganglion cell (RGC) layer and astrocyte 
      phenotypes in the anterior vasculature. The RGC-engrafted cells formed extensions 
      toward the inner nuclear layer. In the presence of growth factors, donor cells 
      migrated to the optic nerve and contributed to repair by gliosis. Mobilization 
      with GM-CSF restricted cell fate to microglia, whereas SCF was associated with 
      limited neuroglial differentiation. CONCLUSIONS: Both BDNF and CNTF enhance 
      engraftment and neuroglial differentiation of adult bone marrow stem cells in 
      injured retina, with BDNF having an early quantitative and qualitative advantage 
      over CNTF. Mobilization with differentiation factors restricts cell fate in the 
      injured retina.
FAU - Goldenberg-Cohen, Nitza
AU  - Goldenberg-Cohen N
AD  - The Krieger Eye Research Laboratory, Felsenstein Medical Research Center, Petach 
      Tikva, Israel.
FAU - Avraham-Lubin, Bat-Chen R
AU  - Avraham-Lubin BC
FAU - Sadikov, Tamilla
AU  - Sadikov T
FAU - Askenasy, Nadir
AU  - Askenasy N
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140129
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Ciliary Neurotrophic Factor)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/*cytology/drug effects
MH  - Brain-Derived Neurotrophic Factor/*administration & dosage
MH  - Cell Count
MH  - Ciliary Neurotrophic Factor/*administration & dosage
MH  - Disease Models, Animal
MH  - Drug Therapy, Combination
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Optic Neuropathy, Ischemic/pathology/*therapy
MH  - *Stem Cell Transplantation
MH  - Treatment Outcome
OTO - NOTNLM
OT  - bone marrow-derived stem cells (BMSC)
OT  - cell migration
OT  - mouse model
OT  - neuronal growth factors
OT  - stem cell differentiation
EDAT- 2013/12/29 06:00
MHDA- 2014/02/26 06:00
CRDT- 2013/12/28 06:00
PHST- 2013/12/28 06:00 [entrez]
PHST- 2013/12/29 06:00 [pubmed]
PHST- 2014/02/26 06:00 [medline]
AID - iovs.13-12223 [pii]
AID - 10.1167/iovs.13-12223 [doi]
PST - epublish
SO  - Invest Ophthalmol Vis Sci. 2014 Jan 29;55(1):502-12. doi: 10.1167/iovs.13-12223.