title: The Effect of Transient Local Anti-inflammatory Treatment on the Survival of Pig Retinal Progenitor Cell Allotransplants.
abstract: OBJECTIVE
  The development of photoreceptor replacement therapy for retinal degenerative disorders requires the identification of the optimal cell source and immunosuppressive regimen in a large animal model. Allotransplants are not acutely rejected in swine subretinal space, although it is not known if survival can be improved with immunosuppression. Here we investigated the survival and integration of expanded pig retinal progenitor cells (pRPCs) in normal recipients with and without transient anti-inflammatory suppression.
  
  
  METHODS
  pRPCs were derived from the neural retina of E60 GFP transgenic pigs, expanded for six passages, characterized, and transplanted into the subretinal space of 12 pigs. Six recipients received a single intravitreal injection of rapamycin and dexamethasone.
  
  
  RESULTS
  pRPCs expressed the photoreceptor development genes Sox2, Pax6, Lhx2, Crx, Nrl, and Recoverin in vitro. Transplanted cells were identified in 9 out of 12 recipients 4 weeks after the injection. pRPCs integrated primarily into the photoreceptor inner segment layer and outer nuclear layer with single cells present in the inner nuclear layer. Donor cells remained recoverin-positive and acquired rhodopsin. We did not observe any signs of graft proliferation. The immunosuppression did not affect the survival or distribution of grafts. No macrophage infiltration or loss of retinal structure was observed in either group.
  
  
  CONCLUSIONS
  Local immunosuppression with rapamycin and dexamethasone does not improve the outcome of pRPC allotransplantation into the subretinal space.
  
  
  CONCLUSIONS
  Survival and integration of pRPC together with the lack of graft proliferation suggests that allogeneic RPC transplantation without transient immunosuppression is a favorable approach for photoreceptor cell replacement.
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear, an affiliate of Harvard Medical School, Boston, MA, USA ; Federal University of Goias, Goiania, Brazil.
authors.forename: Murilo
authors.initials: M
authors.lastname: Abud
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear, an affiliate of Harvard Medical School, Boston, MA, USA.
authors.forename: Petr
authors.initials: P
authors.lastname: Baranov
authors.affiliation: ReNeuron, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Hicks
authors.affiliation: ReNeuron, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Patel
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear, an affiliate of Harvard Medical School, Boston, MA, USA.
authors.forename: Burke
authors.initials: B
authors.lastname: Lieppman
authors.affiliation: Federal University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Caio
authors.initials: C
authors.lastname: Regatieri
authors.affiliation: ReNeuron, UK.
authors.forename: John
authors.initials: J
authors.lastname: Sinden
authors.affiliation: Federal University of Goias, Goiania, Brazil.
authors.forename: David
authors.initials: D
authors.lastname: Isaac
authors.affiliation: Federal University of Goias, Goiania, Brazil.
authors.forename: Marcos
authors.initials: M
authors.lastname: Avila
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear, an affiliate of Harvard Medical School, Boston, MA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Young
keywords: cell therapy; photoreceptors; rapamycin; retina; retinal progenitor cells