Characterization and survival of long-term implants of human retinal pigment epithelial cells attached to gelatin microcarriers in a model of Parkinson disease

J Neuropathol Exp Neurol. 2007 Jul;66(7):585-96. doi: 10.1097/nen.0b013e318093e53a.

Abstract

Previous studies have demonstrated that the intrastriatal implantation of human retinal pigment epithelial cells attached to gelatin microcarriers (hRPE-GM) ameliorates behavioral deficits in animal models of Parkinson disease. However, there are only sparse data on cell survival in the host. In this study, we characterized a variety of retinal pigment epithelial (RPE)-specific markers in vitro and used these markers to investigate the long-term survival of hRPE-GM implants. Sprague-Dawley rats (n = 22) were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and implanted with hRPE-GM without immunosuppression. Rats were euthanized at 48 hours, 7 days, 4 weeks, and 5 months postimplant and immunohistochemically processed using the following antibodies: 1) human-specific nuclear mitotic apparatus protein (NuMA-Ab2), 2) epithelial-specific extracellular matrix metalloproteinase inducer (EMMPRIN), 3) RPE cell-specific RPE65, and the inflammation markers 4) glial fibrillary acidic protein and 5) ED1 (rat CD68). Our analysis revealed NuMA-, EMMPRIN-, and RPE65-immunoreactive cells at different times postimplant. The morphologic features of hRPE cell implants (at 48 hours and 5 months) were confirmed by electron microscopy. Furthermore, despite evidence of chronic inflammation at the later time point, there is an appreciable number of surviving hRPE cells. This study suggests that hRPE-GM implants can survive in the absence of immunosuppression and can be potentially used as an alternative for treating Parkinson disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival
  • Cell Transplantation / methods*
  • Corpus Striatum / pathology*
  • Corpus Striatum / physiopathology
  • Corpus Striatum / surgery
  • Disease Models, Animal
  • Gelatin / therapeutic use
  • Humans
  • Male
  • Microscopy, Electron, Transmission / methods
  • Microspheres
  • Nerve Tissue Proteins / metabolism
  • Parkinson Disease / etiology
  • Parkinson Disease / physiopathology
  • Parkinson Disease / surgery*
  • Pigment Epithelium of Eye* / physiology
  • Pigment Epithelium of Eye* / transplantation
  • Pigment Epithelium of Eye* / ultrastructure
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Transplantation, Heterologous / methods*

Substances

  • Nerve Tissue Proteins
  • Gelatin