title: A Subsequent Human Neural Progenitor Transplant into the Degenerate Retina Does Not Compromise Initial Graft Survival or Therapeutic Efficacy.
abstract: OBJECTIVE
  Stem and progenitor cell transplantation provides a promising clinical application for treating degenerative retinal diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Our previous studies have shown that a single subretinal injection of human cortical-derived neural progenitor cells (hNPCctx) into cyclosporine-treated Royal College of Surgeons (RCS) rats preserved both photoreceptors and visual function. However, it is still unknown whether nonautologous progenitor cell readministration for sustained vision is efficacious and safe in terms of the initial graft initiating an immune response to a subsequent graft.
  
  
  METHODS
  A cell suspension containing 3×104hNPCctxinto one eye of cyclosporine-treated RCS rats at postnatal day 21 (P21), followed by a second transplantation at P95 into the previously untreated fellow eye.
  
  
  RESULTS
  hNPCctxdelayed photoreceptor degeneration and preserved visual function, as measured by electroretinography (ERG), optokinetic response (OKR), and luminance threshold recordings (LTRs). Visual function and photoreceptors of the initially treated eye were still preserved 6 weeks after hNPCctxwere injected into the second eye. Antibodies against T-cell markers showed that CD3, CD4, and CD8 T cells were not detected at P90 and P140 in most cases. No detectable level of anti-nestin antibody was found in serum by enzyme-linked immunosorbent assay (ELISA).
  
  
  CONCLUSIONS
  This xenograft study with cyclosporine-treated animals demonstrates that readministration of hNPCctxinto the fellow eye did not induce anti-graft immune responses or lower therapeutic efficacy of hNPCctxin preserving vision. Thus, readministration of progenitor cells to sustain long-term efficacy may be an option for long-term therapies of retinal degeneration.
  
  
  CONCLUSIONS
  Redosing neural progenitors do not affect the efficacy of the initial grafts in protecting vision or induce unwanted immune responses.
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Tsai
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Sergey
authors.initials: S
authors.lastname: Girman
authors.affiliation: Casey Eye Institute, OHSU, Portland, OR, USA.
authors.forename: Grazyna
authors.initials: G
authors.lastname: Adamus
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Jones
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Shelley
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Clive N
authors.initials: CN
authors.lastname: Svendsen
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Shaomei
authors.initials: S
authors.lastname: Wang
keywords: human neural progenitor cells; immune response; re-dosing; retinal degeneration; transplantation; visual function