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

Lehnen, Daniela; Barral, Serena; Cardoso, Tiago LU ; Grealish, Shane LU ; Heuer, Andreas LU ; Smiyakin, Andrej; Kirkeby, Agnete LU ; Kollet, Jutta; Cremer, Harold and Parmar, Malin LU , et al. (2017) In Stem Cell Reports 9(4). p.1207-1220
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... (More)

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.

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keywords
CD47, Cell replacement therapy, Dopaminergic, Floor plate, IAP, Immunomagnetic sorting (MACS), MesDA progenitor cells, Midbrain, Parkinson's disease, PD, Regenerative medicine
in
Stem Cell Reports
volume
9
issue
4
pages
1207 - 1220
publisher
Cell Press
external identifiers
  • scopus:85029676203
  • wos:000412660000017
ISSN
2213-6711
DOI
10.1016/j.stemcr.2017.08.016
language
English
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yes
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53856e88-a0a7-4f40-bd71-908794be95d6
date added to LUP
2017-10-10 08:26:45
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2018-02-04 04:32:26
@article{53856e88-a0a7-4f40-bd71-908794be95d6,
  abstract     = {<p>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<sup>+</sup> 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<sup>+</sup> cells sorted at day 16 of differentiation in a rat model of PD resulted in functional recovery. Grafts from sorted IAP<sup>+</sup> 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<sup>+</sup> 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.</p>},
  author       = {Lehnen, Daniela and Barral, Serena and Cardoso, Tiago and Grealish, Shane and Heuer, Andreas and Smiyakin, Andrej and Kirkeby, Agnete and Kollet, Jutta and Cremer, Harold and Parmar, Malin and Bosio, Andreas and Knöbel, Sebastian},
  issn         = {2213-6711},
  keyword      = {CD47,Cell replacement therapy,Dopaminergic,Floor plate,IAP,Immunomagnetic sorting (MACS),MesDA progenitor cells,Midbrain,Parkinson's disease,PD,Regenerative medicine},
  language     = {eng},
  number       = {4},
  pages        = {1207--1220},
  publisher    = {Cell Press},
  series       = {Stem Cell Reports},
  title        = {IAP-Based Cell Sorting Results in Homogeneous Transplantable Dopaminergic Precursor Cells Derived from Human Pluripotent Stem Cells},
  url          = {http://dx.doi.org/10.1016/j.stemcr.2017.08.016},
  volume       = {9},
  year         = {2017},
}