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Neonatal human retinal pigment epithelial cells secrete limited trophic factors in vitro and in vivo following striatal implantation in parkinsonian rats

  • Translational Neurosciences - Original Article
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Abstract

Human retinal pigment epithelial (hRPE) cell implants into the striatum have been investigated as a potential cell-based treatment for Parkinson’s disease in a Phase II clinical trial that recently failed. We hypothesize that the trophic factor potential of the hRPE cells could potentially influence the function and/or survival of the implants and may be involved in an alternative mechanism of action. However, it is unclear if hRPE cells secreted trophic factors when handled in the manner used in the clinical Phase II trial. To address these questions, we investigated two neonatal hRPE cell lots, cultured in a similar manner to hRPE cells used in a Phase II clinical study, and longitudinally determined brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2), and pigment epithelium-derived factor concentrations in vitro and following striatal implantation into 6-hydroxydopamine-lesioned rats. The results demonstrate short-lived BDNF and FGF2 concentrations in vitro from hRPE cells grown alone or attached to gelatin microcarriers (GM)s as well as limited trophic factor concentration differences in vivo following striatal implantation of hRPE-GM in 6-hydroxydopamine lesioned rats compared to sham (GM-only). The data suggest that trophic factors from neonatal hRPE cell implants likely did not participate in an alternative mechanism of action, which adds supports to a hypothesis that additional factors may have been necessary for the survival and/or function of hRPE implants and potentially the success of the Phase II clinical trial.

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Acknowledgments

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. We also thank Dr. Brian McKay from University of Arizona and Dr. Luba Kojic from University of British Columbia for CM from fetal hRPE cell and HeLa cells, respectively, which were used as controls. Additionally, we thank Wesley Mah, 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 recognize 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. Neonatal human retinal pigment epithelial cells secrete limited trophic factors in vitro and in vivo following striatal implantation in parkinsonian rats. J Neural Transm 123, 167–177 (2016). https://doi.org/10.1007/s00702-015-1480-7

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  • DOI: https://doi.org/10.1007/s00702-015-1480-7

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