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Recovery of Neurological Functions in Non-Human Primate Model of Parkinson's Disease by Transplantation of Encapsulated Neonatal Porcine Choroid Plexus Cells

Article type: Research Article

Authors: Luo, Xian-Ming | Lin, Hai | Wang, Wei | Geaney, Marilyn S. | Law, Lee | Wynyard, Shaun | Shaikh, Shamim B. | Waldvogel, Henry | Faull, Richard L.M. | Elliott, Robert B. | Skinner, Stephen J.M. | Lee, Jacqueline E. | Tan, Paul L.-J.

Affiliations: The Third Xianya Hospital of Central-South University, Changsha, China | Living Cell Technologies Limited, Papatoetoe, Auckland, New Zealand | School of Medical Sciences, University of Auckland, Auckland, New Zealand | Department of Physiology, University of Auckland, Auckland, New Zealand

Note: [] Correspondence to: Wei Wang, The Third Xianya Hospital of Central-South University, Changsha, China. Tel.: +64 9 270 7948; Fax: +64 9 276 2691; E-mail: [email protected]

Note: [] Correspondence to: Paul L.-J. Tan, Living Cell Technologies Limited, Papatoetoe, Auckland, New Zealand. E-mail: [email protected]

Keywords: Parkinson's disease (PD), MPTP, apomorphine, monkey, choroid plexus (CP), encapsulated choroid plexus clusters (eCPs), neurotrophin, substantia nigra (SN), striatum, putamen, TH fibre, encapsulation, motor control, neurological recovery, dopaminergic, tyrosine hydroxylase

DOI: 10.3233/JPD-130214

Journal: Journal of Parkinson's Disease, vol. 3, no. 3, pp. 275-291, 2013

Published: 2013
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Supplemental Materials.

Abstract

Parkinson's disease (PD) is a neurodegenerative disease that is primarily characterized by degeneration of dopaminergic (DA) neurons in the substantia nigra (SN) and a loss of their fibre projections in the striatum. We utilized the neonatal porcine choroid plexus (CP), an organ that secretes cerebrospinal fluid containing various types of neurotrophic and neuroprotective factors, to ameliorate the Parkinsonian symptoms in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated rhesus monkeys without requiring immunosuppression. We demonstrate that transplanted encapsulated CP clusters (eCPs) significantly improved neurological functions in MPTP-treated monkeys during the course of six months after transplantation (p < 0.001) when compared with monkeys implanted with empty capsules or subjected to sham surgery. The improvement in neurological scores was accompanied by a corresponding improvement in apomorphine-induced circling behaviour (p < 0.001) as well as increased tyrosine hydroxylase (TH) staining in the striatum. Our results suggest that eCPs are a promising cell therapeutic agent to treat Parkinson's disease.

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