Differential behavioral outcomes following neonatal versus fetal human retinal pigment epithelial cell striatal implants in parkinsonian rats

Abstract

Following the failure of a Phase II clinical study evaluating human retinal pigment epithelial (hRPE) cell implants as a potential treatment option for Parkinson’s disease, speculation has centered on implant function and survival as possible contributors to the therapeutic outcomes. We recently reported that neonatal hRPE cells, similar to hRPE cells used in the Phase II clinical study, produced short-lived in vitro and limited in vivo trophic factors, which supports that assumption. We hypothesize that the switch from fetal to neonatal hRPE cells, between the Phase I and the Phase II clinical trial may be partly responsible for the later negative outcomes. To investigate this hypothesis, we used two neonatal hRPE cell lots, prepared in a similar manner to neonatal hRPE cells used in the Phase II clinical study, and compared them to previously evaluated fetal hRPE cells for behavioral changes following unilateral striatal implantation in 6-hydroxydopamine-lesioned rats. The results showed that only fetal, not neonatal, hRPE cell implants, were able to improve behavioral outcomes following striatal implantation in the lesioned rats. These data suggest that fetal hRPE cells may be preferential to neonatal hRPE cells in restoring behavioral deficits.

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Acknowledgements

This research was supported by a grant from the UBC-CIHR Training Program in Transplantation. We would like to thank Dr. Michael Cornfeldt from Titan Pharmaceuticals and Dr. Branka Mitrovic from Bayer Schering Pharma for the gift of hRPE cells and microcarriers, which allowed these studies to be performed. Additionally, we thank Wesley Mah for assistance with behavioral evaluations and Rick Kornelsen, Chenoa Mah, and the personnel of the UBC Animal Resources Unit for technical assistance and support with the animals. Lastly, we want to acknowledge Dr. Bente Pakkenberg for her critical review of the manuscript.

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Correspondence to Kaspar Russ.

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Russ, K., Flores, J., Brudek, T. et al. Differential behavioral outcomes following neonatal versus fetal human retinal pigment epithelial cell striatal implants in parkinsonian rats. J Neural Transm 124, 455–462 (2017). https://doi.org/10.1007/s00702-017-1683-1

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Keywords

  • Retinal pigment epithelial cells
  • Parkinson’s disease
  • Neonatal
  • Fetal
  • Cell transplantation
  • 6-hydroxydopamine