Characterization of CDNF-Secreting ARPE-19 Cell Clones for Encapsulated Cell Therapy

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Galli , E , Lindholm , P , Kontturi , L-S , Saarma , M , Urtti , A & Yliperttula , M 2019 , ' Characterization of CDNF-Secreting ARPE-19 Cell Clones for Encapsulated Cell Therapy ' , Cell Transplantation , vol. 28 , no. 4 , pp. 413-424 . https://doi.org/10.1177/0963689719827943

Title: Characterization of CDNF-Secreting ARPE-19 Cell Clones for Encapsulated Cell Therapy
Author: Galli, Emilia; Lindholm, Päivi; Kontturi, Leena-Stiina; Saarma, Mart; Urtti, Arto; Yliperttula, Marjo
Other contributor: University of Helsinki, Division of Pharmaceutical Biosciences
University of Helsinki, Institute of Biotechnology
University of Helsinki, Divisions of Faculty of Pharmacy
University of Helsinki, Mart Saarma / Principal Investigator
University of Helsinki, Drug Research Program
University of Helsinki, Division of Pharmaceutical Biosciences








Date: 2019-04
Language: eng
Number of pages: 12
Belongs to series: Cell Transplantation
ISSN: 0963-6897
DOI: https://doi.org/10.1177/0963689719827943
URI: http://hdl.handle.net/10138/304410
Abstract: Cerebral Dopamine Neurotrophic Factor (CDNF) shows beneficial effects in rodent models of Parkinson?s and Alzheimer?s disease. The brain is a challenging target for protein therapy due to its exclusive blood?brain barrier. Hence, the therapeutic protein should be delivered directly to the brain parenchyma. Implantation of encapsulated mammalian cells that constantly secrete CDNF is a potential approach for targeted and long-term protein delivery to the brain. In this study, we generated several CDNF-secreting cell clones derived from human retinal pigment epithelial cell line ARPE-19, and studied CDNF secretion from the clones maintained as monolayers and in polymeric microcapsules. The secretion of wild type (wt) CDNF transgene was low and the majority of the produced protein remained intracellular, locating mainly to the endoplasmic reticulum (ER). The secretion of wtCDNF decreased to even lower levels when the clones were in a non-dividing state, as in the microcapsules. Both codon optimization and deletion of the putative ER-retrieval signal (four last amino acids: KTEL) improved CDNF secretion. More importantly, the secretion of KTEL-deleted CDNF remained constant in the non-dividing clones. Thus, cells expressing KTEL-deleted CDNF, in contrast to wtCDNF, can be considered for cell encapsulation applications if the KTEL-deleted CDNF is proven to be biologically active in vivo.
Subject: BIODELIVERY
CDNF
CILIARY NEUROTROPHIC FACTOR
CNTF
DEGENERATION
DELIVERY
ER localization
LINE
MANF
MIDBRAIN DOPAMINE NEURONS
PROTECTS
RAT MODEL
cell encapsulation
codon optimization
secretion
1182 Biochemistry, cell and molecular biology
3111 Biomedicine
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