Please use this identifier to cite or link to this item: https://doi.org/10.1186/s13287-018-1061-4
Title: The prostaglandin H2 analog U-46619 improves the differentiation efficiency of human induced pluripotent stem cells into endothelial cells by activating both p38MAPK and ERK1/2 signaling pathways
Authors: Su, L.
Kong, X.
Lim, S.
Loo, S.
Tan, S.
Poh, K. 
Dutton, J.
Stewart, C.
Cook, S. 
Su, X.
Ma, J.
Zhang, J.
Ye, L. 
Keywords: 15 hydroxy 11alpha,9alpha epoxymethanoprosta 5,13 dienoic acid
6 [[2 [[4 (2,4 dichlorophenyl) 5 (4 methyl 1h imidazol 2 yl) 2 pyrimidinyl]amino]ethyl]amino]nicotinonitrile
mitogen activated protein kinase p38
pyridine derivative
pyrimidine derivative
animal
cell differentiation
cell line
cytology
disease model
drug effect
endothelium cell
enzyme activation
enzymology
hindlimb
human
induced pluripotent stem cell
ischemia
MAPK signaling
mesoderm
metabolism
nonobese diabetic mouse
pathology
perfusion
SCID mouse
vascularization
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Animals
Cell Differentiation
Cell Line
Disease Models, Animal
Endothelial Cells
Enzyme Activation
Hindlimb
Humans
Induced Pluripotent Stem Cells
Ischemia
MAP Kinase Signaling System
Mesoderm
Mice, Inbred NOD
Mice, SCID
p38 Mitogen-Activated Protein Kinases
Perfusion
Pyridines
Pyrimidines
Issue Date: 2018
Publisher: BioMed Central Ltd.
Citation: Su, L., Kong, X., Lim, S., Loo, S., Tan, S., Poh, K., Dutton, J., Stewart, C., Cook, S., Su, X., Ma, J., Zhang, J., Ye, L. (2018). The prostaglandin H2 analog U-46619 improves the differentiation efficiency of human induced pluripotent stem cells into endothelial cells by activating both p38MAPK and ERK1/2 signaling pathways. Stem cell research & therapy 9 (1) : 313. ScholarBank@NUS Repository. https://doi.org/10.1186/s13287-018-1061-4
Abstract: BACKGROUND: We have shown that the differentiation of human-induced pluripotent stem cells (hiPSCs) into endothelial cells (ECs) is more efficient when performed with a 3-dimensional (3D) scaffold of biomaterial than in monolayers. The current study aims to further increase hiPSC-EC differentiation efficiency by deciphering the signaling pathways in 3D scaffolds. METHODS AND RESULTS: We modified our 3D protocol by using U-46619 to upregulate both p38 mitogen-activated protein kinase (p38MAPK) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, which increased the differentiation efficiency (as measured by CD31 expression) to as high as 89% in two established hiPSC lines. The differentiated cells expressed arteriovenous, but not lymphatic, markers; formed tubular structures and EC lumen in vitro; had significantly shorter population-doubling times than monolayer-differentiated hiPSC-ECs; and restored perfusion and vascularity in a murine hind limb ischemia model. The differentiation efficiency was also>?85% in three hiPSC lines that had been derived from patients with diseases or disease symptoms that have been linked to endothelial dysfunction. CONCLUSIONS: These observations demonstrate that activating both p38MAPK and ERK1/2 signaling pathways with U-46619 improves the efficiency of arteriovenous hiPSC-EC differentiation and produces cells with greater proliferative capacity.
Source Title: Stem cell research & therapy
URI: https://scholarbank.nus.edu.sg/handle/10635/174517
ISSN: 17576512
DOI: 10.1186/s13287-018-1061-4
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