title: Effect of coadministration of neuronal growth factors on neuroglial differentiation of bone marrow-derived stem cells in the ischemic retina.
abstract: OBJECTIVE
  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.
authors.affiliation: The Krieger Eye Research Laboratory, Felsenstein Medical Research Center, Petach Tikva, Israel.
authors.forename: Nitza
authors.initials: N
authors.lastname: Goldenberg-Cohen
authors.forename: Bat-Chen R
authors.initials: BC
authors.lastname: Avraham-Lubin
authors.forename: Tamilla
authors.initials: T
authors.lastname: Sadikov
authors.forename: Nadir
authors.initials: N
authors.lastname: Askenasy
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage*; D002452:Cell Count; D020934:Ciliary Neurotrophic Factor / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018917:Optic Neuropathy, Ischemic / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation; D016896:Treatment Outcome
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor
keywords: bone marrow–derived stem cells (BMSC); cell migration; mouse model; neuronal growth factors; stem cell differentiation