[PDF][PDF] IAP-based cell sorting results in homogeneous transplantable dopaminergic precursor cells derived from human pluripotent stem cells

D Lehnen, S Barral, T Cardoso, S Grealish, A Heuer… - Stem Cell Reports, 2017 - cell.com
D Lehnen, S Barral, T Cardoso, S Grealish, A Heuer, A Smiyakin, A Kirkeby, J Kollet
Stem Cell Reports, 2017cell.com
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 …
Summary
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.
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