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

Research output: Contribution to journalArticle

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. 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.

Details

Authors
Organisations
External organisations
  • Miltenyi Biotec GmbH
  • Aix-Marseille University
  • University College London
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • 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
Original languageEnglish
Pages (from-to)1207-1220
JournalStem Cell Reports
Volume9
Issue number4
Publication statusPublished - 2017
Publication categoryResearch
Peer-reviewedYes