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Stem Cell Reports. 2017 Oct 10;9(4):1207-1220. doi: 10.1016/j.stemcr.2017.08.016. Epub 2017 Sep 21.

IAP-Based Cell Sorting Results in Homogeneous Transplantable Dopaminergic Precursor Cells Derived from Human Pluripotent Stem Cells.

Author information

1
Miltenyi Biotec GmbH, 51429 Bergisch Gladbach, Germany.
2
Aix-Marseille University, CNRS, IBDM; Campus de Luminy, 13009 Marseille, France.
3
Developmental and Regenerative Neurobiology, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, 22184 Lund, Sweden.
4
Miltenyi Biotec GmbH, 51429 Bergisch Gladbach, Germany. Electronic address: sebastian.knoebel@miltenyibiotec.de.

Abstract

Human pluripotent stem cell (hPSC)-derived mesencephalic dopaminergic (mesDA) neurons can relieve motor deficits in animal models of Parkinson's disease (PD). Clinical translation of differentiation protocols requires standardization of production procedures, and surface-marker-based cell sorting is considered instrumental for reproducible generation of defined cell products. Here, we demonstrate that integrin-associated protein (IAP) is a cell surface marker suitable for enrichment of hPSC-derived mesDA progenitor cells. Immunomagnetically sorted IAP+ mesDA progenitors showed increased expression of ventral midbrain floor plate markers, lacked expression of pluripotency markers, and differentiated into mature dopaminergic (DA) neurons in vitro. Intrastriatal transplantation of IAP+ cells sorted at day 16 of differentiation in a rat model of PD resulted in functional recovery. Grafts from sorted IAP+ mesDA progenitors were more homogeneous in size and DA neuron density. Thus, we suggest IAP-based sorting for reproducible prospective enrichment of mesDA progenitor cells in clinical cell replacement strategies.

KEYWORDS:

CD47; IAP; PD; Parkinson's disease; cell replacement therapy; dopaminergic; floor plate; immunomagnetic sorting (MACS); mesDA progenitor cells; midbrain; regenerative medicine

PMID:
28943253
PMCID:
PMC5639383
DOI:
10.1016/j.stemcr.2017.08.016
[Indexed for MEDLINE]
Free PMC Article

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