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Proc Natl Acad Sci U S A. 2015 Apr 14;112(15):E1946-55. doi: 10.1073/pnas.1501989112. Epub 2015 Mar 9.

Transcriptome analysis reveals transmembrane targets on transplantable midbrain dopamine progenitors.

Author information

  • 1Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia 3010; and.
  • 2Wallenberg Neuroscience Centre, Department of Experimental Medical Science, Lund University, S-22184 Lund, Sweden.
  • 3Wallenberg Neuroscience Centre, Department of Experimental Medical Science, Lund University, S-22184 Lund, Sweden anders.bjorklund@med.lu.se lachlant@unimelb.edu.au.
  • 4Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia 3010; and anders.bjorklund@med.lu.se lachlant@unimelb.edu.au.

Abstract

An important challenge for the continued development of cell therapy for Parkinson's disease (PD) is the establishment of procedures that better standardize cell preparations for use in transplantation. Although cell sorting has been an anticipated strategy, its application has been limited by lack of knowledge regarding transmembrane proteins that can be used to target and isolate progenitors for midbrain dopamine (mDA) neurons. We used a "FACS-array" approach to identify 18 genes for transmembrane proteins with high expression in mDA progenitors and describe the utility of four of these targets (Alcam, Chl1, Gfra1, and Igsf8) for isolating mDA progenitors from rat primary ventral mesencephalon through flow cytometry. Alcam and Chl1 facilitated a significant enrichment of mDA neurons following transplantation, while targeting of Gfra1 allowed for robust separation of dopamine and serotonin neurons. Importantly, we also show that mDA progenitors isolated on the basis of transmembrane proteins are capable of extensive, functional innervation of the host striatum and correction of motor impairment in a unilateral model of PD. These results are highly relevant for current efforts to establish safe and effective stem cell-based procedures for PD, where clinical translation will almost certainly require safety and standardization measures in order to deliver well-characterized cell preparations.

KEYWORDS:

Alcam; Parkinson’s disease; cell sorting; microarray; transplantation

PMID:
25775569
PMCID:
PMC4403171
DOI:
10.1073/pnas.1501989112
[PubMed - indexed for MEDLINE]
Free PMC Article

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