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

TY - JOUR

T1 - IAP-Based Cell Sorting Results in Homogeneous Transplantable Dopaminergic Precursor Cells Derived from Human Pluripotent Stem Cells.

AU - Lehnen, Daniela

AU - Barral, Serena

AU - Cardoso, Tiago

AU - Grealish, Shane

AU - Heuer, Andreas

AU - Smiyakin, Andrej

AU - Kirkeby, Agnete

AU - Kollet, Jutta

AU - Cremer, Harold

AU - Parmar, Malin

AU - Bosio, Andreas

AU - Knoebel, Sebastian.

N1 - M1 - Copyright (C) 2018 American Chemical Society (ACS). All Rights Reserved. CAPLUS AN 2017:1573803(Journal; Online Computer File)

PY - 2017/10/10

Y1 - 2017/10/10

N2 - 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. In this article, Knöbel and colleagues identified IAP as a cell surface marker for mesDA progenitor cells. Immunomagnetic sorting for IAP+ led to reproducible and homogeneous cell compositions. Intrastriatal transplantation of sorted cells at day 16 of differentiation in a PD rat model resulted in functional recovery, and grafts were more homogeneous in size and DA neuron density than unsorted cells.

AB - 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. In this article, Knöbel and colleagues identified IAP as a cell surface marker for mesDA progenitor cells. Immunomagnetic sorting for IAP+ led to reproducible and homogeneous cell compositions. Intrastriatal transplantation of sorted cells at day 16 of differentiation in a PD rat model resulted in functional recovery, and grafts were more homogeneous in size and DA neuron density than unsorted cells.

U2 - 10.1016/j.stemcr.2017.08.016

DO - 10.1016/j.stemcr.2017.08.016

M3 - Journal article

C2 - 28943253

SN - 2213-6711

VL - 9

SP - 1207

EP - 1220

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 4

ER -