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Andreas Heuer

Andreas Heuer

Research team manager

Andreas Heuer

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

Author

  • Daniela Lehnen
  • Serena Barral
  • Tiago Cardoso
  • Shane Grealish
  • Andreas Heuer
  • Andrej Smiyakin
  • Agnete Kirkeby
  • Jutta Kollet
  • Harold Cremer
  • Malin Parmar
  • Andreas Bosio
  • Sebastian Knöbel
Show all

Summary, in English

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.

Department/s

  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
  • MultiPark: Multidisciplinary research focused on Parkinson´s disease
  • Developmental and Regenerative Neurobiology
  • Department of Experimental Medical Science
  • Human Neural Developmental Biology

Publishing year

2017

Language

English

Pages

1207-1220

Publication/Series

Stem Cell Reports

Volume

9

Issue

4

Document type

Journal article

Publisher

Cell Press

Topic

  • Cell and Molecular Biology
  • Neurosciences

Keywords

  • CD47
  • Cell replacement therapy
  • Dopaminergic
  • Floor plate
  • IAP
  • Immunomagnetic sorting (MACS)
  • MesDA progenitor cells
  • Midbrain
  • Parkinson's disease
  • PD
  • Regenerative medicine

Status

Published

Research group

  • Developmental and Regenerative Neurobiology
  • Human Neural Developmental Biology

ISBN/ISSN/Other

  • ISSN: 2213-6711