TY - JOUR

T1 - Differentiation of Human Pluripotent Stem Cells into Functional Endothelial Cells in Scalable Suspension Culture

AU - Olmer, Ruth

AU - Engels, Lena

AU - Usman, Abdulai

AU - Menke, Sandra

AU - Malik, Muhammad Nasir Hayat

AU - Pessler, Frank

AU - Göhring, Gudrun

AU - Bornhorst, Dorothee

AU - Bolten, Svenja

AU - Abdelilah-Seyfried, Salim

AU - Scheper, Thomas

AU - Kempf, Henning

AU - Zweigerdt, Robert

AU - Martin, Ulrich

N1 - Funding information: We thank Dr. A. Haase for providing hiPSCs, Dr K. Osetek for isolation of hUVEC as well as hCBECs, and M. Szepes for performing tube-forming assay of hUVECs. We thank M. Lönne and A. Franke for technical assistance. This work was funded by the German Research Foundation ( KFO311 , MA 2331/18-1 ; MA 2331/15-1 , SFB958 , SE2016/7-2 , SE2016/10-1 , ZW64/4-1 , and KFO311- ZW64/7-1 ), the German Center for Lung Research (DZL, BREATH 82DZL002A1 ), and the German Research Foundation (Cluster of Excellence REBIRTH, EXC 62), by the German Ministry for Education and Science (BMBF, grants: 13N14086 , 01EK1601A , and 01EK1602A ), by the European Union (TECHNOBEAT, grant 668724 ), and by StemBANCC (receiving support from the Innovative Medicines Initiative joint undertaking under grant 115439-2 , whose resources are composed of financial contribution from the European Union [ FP7/2007-2013 ] and EFPIA companies' in-kind contribution).

PY - 2018/4/19

Y1 - 2018/4/19

N2 - Endothelial cells (ECs) are involved in a variety of cellular responses. As multifunctional components of vascular structures, endothelial (progenitor) cells have been utilized in cellular therapies and are required as an important cellular component of engineered tissue constructs and in vitro disease models. Although primary ECs from different sources are readily isolated and expanded, cell quantity and quality in terms of functionality and karyotype stability is limited. ECs derived from human induced pluripotent stem cells (hiPSCs) represent an alternative and potentially superior cell source, but traditional culture approaches and 2D differentiation protocols hardly allow for production of large cell numbers. Aiming at the production of ECs, we have developed a robust approach for efficient endothelial differentiation of hiPSCs in scalable suspension culture. The established protocol results in relevant numbers of ECs for regenerative approaches and industrial applications that show in vitro proliferation capacity and a high degree of chromosomal stability. In this article, U. Martin and colleagues show the generation of hiPSC endothelial cells in scalable cultures in up to 100 mL culture volume. The generated ECs show in vitro proliferation capacity and a high degree of chromosomal stability after in vitro expansion. The established protocol allows to generate hiPSC-derived ECs in relevant numbers for regenerative approaches.

AB - Endothelial cells (ECs) are involved in a variety of cellular responses. As multifunctional components of vascular structures, endothelial (progenitor) cells have been utilized in cellular therapies and are required as an important cellular component of engineered tissue constructs and in vitro disease models. Although primary ECs from different sources are readily isolated and expanded, cell quantity and quality in terms of functionality and karyotype stability is limited. ECs derived from human induced pluripotent stem cells (hiPSCs) represent an alternative and potentially superior cell source, but traditional culture approaches and 2D differentiation protocols hardly allow for production of large cell numbers. Aiming at the production of ECs, we have developed a robust approach for efficient endothelial differentiation of hiPSCs in scalable suspension culture. The established protocol results in relevant numbers of ECs for regenerative approaches and industrial applications that show in vitro proliferation capacity and a high degree of chromosomal stability. In this article, U. Martin and colleagues show the generation of hiPSC endothelial cells in scalable cultures in up to 100 mL culture volume. The generated ECs show in vitro proliferation capacity and a high degree of chromosomal stability after in vitro expansion. The established protocol allows to generate hiPSC-derived ECs in relevant numbers for regenerative approaches.

KW - endothelial cells

KW - hiPSC differentiation

KW - scalable culture

UR - http://www.scopus.com/inward/record.url?scp=85045438454&partnerID=8YFLogxK

U2 - 10.1016/j.stemcr.2018.03.017

DO - 10.1016/j.stemcr.2018.03.017

M3 - Article

C2 - 29681541

AN - SCOPUS:85045438454

VL - 10

SP - 1657

EP - 1672

JO - Stem cell reports

JF - Stem cell reports

SN - 2213-6711

IS - 5

ER -