title: Establishment of a translational endothelial cell model using directed differentiation of induced pluripotent stem cells from Cynomolgus monkey.
abstract: Due to their broad differentiation potential, pluripotent stem cells (PSCs) offer a promising approach for generating relevant cellular models for various applications. While human PSC-based cellular models are already advanced, similar systems for non-human primates (NHPs) are still lacking. However, as NHPs are the most appropriate animals for evaluating the safety of many novel pharmaceuticals, the availability of in vitro systems would be extremely useful to bridge the gap between cellular and animal models. Here, we present a NHP in vitro endothelial cell system using induced pluripotent stem cells (IPSCs) from Cynomolgus monkey (Macaca fascicularis). Based on an adapted protocol for human IPSCs, we directly differentiated macaque IPSCs into endothelial cells under chemically defined conditions. The resulting endothelial cells can be enriched using immuno-magnetic cell sorting and display endothelial marker expression and function. RNA sequencing revealed that the differentiation process closely resembled vasculogenesis. Moreover, we showed that endothelial cells derived from macaque and human IPSCs are highly similar with respect to gene expression patterns and key endothelial functions, such as inflammatory responses. These data demonstrate the power of IPSC differentiation technology to generate defined cell types for use as translational in vitro models to compare cell type-specific responses across species.
authors: Roche pRED (Pharmaceutical Research and Early Development), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors: Eva C
authors: EC
authors: Thoma
authors: Roche pRED (Pharmaceutical Research and Early Development), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors: Tobias
authors: T
authors: Heckel
authors: Roche pRED (Pharmaceutical Research and Early Development), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors: David
authors: D
authors: Keller
authors: Roche pRED (Pharmaceutical Research and Early Development), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors: Nicolas
authors: N
authors: Giroud
authors: Roche pRED (Pharmaceutical Research and Early Development), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors: Brian
authors: B
authors: Leonard
authors: Roche pRED (Pharmaceutical Research and Early Development), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors: Klaus
authors: K
authors: Christensen
authors: Roche pRED (Pharmaceutical Research and Early Development), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors: Adrian
authors: A
authors: Roth
authors: Roche pRED (Pharmaceutical Research and Early Development), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors: Cristina
authors: C
authors: Bertinetti-Lapatki
authors: Roche pRED (Pharmaceutical Research and Early Development), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors: Martin
authors: M
authors: Graf
authors: Roche pRED (Pharmaceutical Research and Early Development), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors: Christoph
authors: C
authors: Patsch
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male
chemical_list: D015415:Biomarkers; D055415:Bone Morphogenetic Protein 4; D017493:Leukocyte Common Antigens