Reenacting Neuroectodermal Exposure of Hematopoietic Progenitors Enables Scalable Production of Cryopreservable iPSC-Derived Human Microglia.

Bioreactor Human microglia In vitro differentiation Induced pluripotent stem cells Macrocarrier

Journal

Stem cell reviews and reports
ISSN: 2629-3277
Titre abrégé: Stem Cell Rev Rep
Pays: United States
ID NLM: 101752767

Informations de publication

Date de publication:
02 2023
Historique:
accepted: 19 07 2022
pubmed: 16 8 2022
medline: 9 2 2023
entrez: 15 8 2022
Statut: ppublish

Résumé

Human microglia, as innate immune cells of the central nervous system (CNS), play a central role in the pathogenesis of a large number of neurological and psychiatric disorders. However, experimental access to primary human microglia for biomedical applications such as disease modeling is extremely limited. While induced pluripotent stem cells (iPSCs) could provide an alternative source of microglia, the reenactment of their complex ontogenesis with a yolk sac origin and subsequent priming upon CNS invasion has remained a challenge. Here, we report a developmentally informed in vitro differentiation method for large-scale production and cryopreservation of iPSC-derived microglia (iPSdMiG). Specifically, iPSCs were propagated in conditions yielding both yolk sac hematopoietic derivatives and early neuroepithelial cells. To enable large-scale production, we implemented 3D bioreactor-based dynamic culture conditions and the use of novel mesh macrocarriers. Under these conditions, microglia could be harvested across a time period of at least 6 weeks, with 1 × 10

Identifiants

pubmed: 35971018
doi: 10.1007/s12015-022-10433-w
pii: 10.1007/s12015-022-10433-w
pmc: PMC9902330
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

455-474

Informations de copyright

© 2022. The Author(s).

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Auteurs

Mona Mathews (M)

LIFE & BRAIN GmbH, Venusberg-Campus 1, 53127, Bonn, Germany.
Institute of Reconstructive Neurobiology, University of Bonn Medical Faculty and University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Jannis Wißfeld (J)

Institute of Reconstructive Neurobiology, Neural Regeneration Group, University of Bonn Medical Faculty and University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Lea Jessica Flitsch (LJ)

Institute of Reconstructive Neurobiology, University of Bonn Medical Faculty and University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Anahita Shahraz (A)

Institute of Reconstructive Neurobiology, Neural Regeneration Group, University of Bonn Medical Faculty and University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Vesselina Semkova (V)

Institute of Reconstructive Neurobiology, University of Bonn Medical Faculty and University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Yannik Breitkreuz (Y)

LIFE & BRAIN GmbH, Venusberg-Campus 1, 53127, Bonn, Germany.
Institute of Reconstructive Neurobiology, University of Bonn Medical Faculty and University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Harald Neumann (H)

Institute of Reconstructive Neurobiology, Neural Regeneration Group, University of Bonn Medical Faculty and University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.

Oliver Brüstle (O)

LIFE & BRAIN GmbH, Venusberg-Campus 1, 53127, Bonn, Germany. brustle@uni-bonn.de.
Institute of Reconstructive Neurobiology, University of Bonn Medical Faculty and University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany. brustle@uni-bonn.de.

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