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@article{1670443,
author = {Farkaš, Šimon and Šimara, Pavel and Řeháková, Daniela and Veverková, Lenka and Koutná, Irena},
article_location = {Lausanne},
article_number = {309},
doi = {http://dx.doi.org/10.3389/fcell.2020.00309},
keywords = {hiPSC; hESC; hPSC; mesoderm; endothelial progenitors; differentiation; protocol},
language = {eng},
issn = {2296-634X},
journal = {Frontiers in Cell and Developmental Biology},
title = {Endothelial Progenitor Cells Produced From Human Pluripotent Stem Cells by a Synergistic Combination of Cytokines, Small Compounds, and Serum-Free Medium},
url = {https://www.frontiersin.org/articles/10.3389/fcell.2020.00309/full},
volume = {8},
year = {2020}
}
TY - JOUR
ID - 1670443
AU - Farkaš, Šimon - Šimara, Pavel - Řeháková, Daniela - Veverková, Lenka - Koutná, Irena
PY - 2020
TI - Endothelial Progenitor Cells Produced From Human Pluripotent Stem Cells by a Synergistic Combination of Cytokines, Small Compounds, and Serum-Free Medium
JF - Frontiers in Cell and Developmental Biology
VL - 8
IS - 309
SP - 1-15
EP - 1-15
PB - Frontiers Media S.A.
SN - 2296634X
KW - hiPSC
KW - hESC
KW - hPSC
KW - mesoderm
KW - endothelial progenitors
KW - differentiation
KW - protocol
UR - https://www.frontiersin.org/articles/10.3389/fcell.2020.00309/full
L2 - https://www.frontiersin.org/articles/10.3389/fcell.2020.00309/full
N2 - Human pluripotent stem cells (hPSCs) are a promising source of autologous endothelial progenitor cells (EPCs) that can be used for the treatment of vascular diseases. However, this kind of treatment requires a large amount of EPCs. Therefore, a highly efficient, robust, and easily reproducible differentiation protocol is necessary. We present a novel serum-free differentiation protocol that exploits the synergy of multiple powerful differentiation effectors. Our protocol follows the proper physiological pathway by differentiating EPCs from hPSCs in three phases that mimic in vivo embryonic vascular development. Specifically, hPSCs are differentiated into (i) primitive streak, which is subsequently turned into (ii) mesoderm, which finally differentiates into (iii) EPCs. This differentiation process yields up to 15 differentiated cells per seeded hPSC in 5 days. Endothelial progenitor cells constitute up to 97% of these derived cells. The experiments were performed on the human embryonic stem cell line H9 and six human induced pluripotent stem cell lines generated in our laboratory. Therefore, robustness was verified using many hPSC lines. Two previously established protocols were also adapted and compared to our synergistic three-phase protocol. Increased efficiency and decreased variability were observed for our differentiation protocol in comparison to the other tested protocols. Furthermore, EPCs derived from hPSCs by our protocol expressed the high-proliferative-potential EPC marker CD157 on their surface in addition to the standard EPC surface markers CD31, CD144, CD34, KDR, and CXCR4. Our protocol enables efficient fully defined production of autologous endothelial progenitors for research and clinical applications.
ER -
FARKAŠ, Šimon, Pavel ŠIMARA, Daniela ŘEHÁKOVÁ, Lenka VEVERKOVÁ and Irena KOUTNÁ. Endothelial Progenitor Cells Produced From Human Pluripotent Stem Cells by a Synergistic Combination of Cytokines, Small Compounds, and Serum-Free Medium. \textit{Frontiers in Cell and Developmental Biology}. Lausanne: Frontiers Media S.A., 2020, vol.~8, No~309, p.~1-15. ISSN~2296-634X. Available from: https://dx.doi.org/10.3389/fcell.2020.00309.
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