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Lowering the increased intracellular pH of human-induced pluripotent stem cell-derived endothelial cells induces formation of mature Weibel-Palade bodies
- Source :
- Stem Cells Translational Medicine, Stem Cells Translational Medicine, Vol 9, Iss 7, Pp 758-772 (2020), Stem Cells Translational Medicine, 9(7), 758-772. WILEY
- Publication Year :
- 2020
- Publisher :
- WILEY, 2020.
-
Abstract
- Differentiation of human‐induced pluripotent stem cells (hiPSCs) into vascular endothelium is of great importance to tissue engineering, disease modeling, and use in regenerative medicine. Although differentiation of hiPSCs into endothelial‐like cells (hiPSC‐derived endothelial cells [hiPSC‐ECs]) has been demonstrated before, controversy exists as to what extent these cells faithfully reflect mature endothelium. To address this issue, we investigate hiPSC‐ECs maturation by their ability to express von Willebrand factor (VWF) and formation of Weibel‐Palade bodies (WPBs). Using multiple hiPSCs lines, hiPSC‐ECs failed to form proper VWF and WPBs, essential for angiogenesis, primary and secondary homeostasis. Lowering the increased intracellular pH (pHi) of hiPSC‐ECs with acetic acid did result in the formation of elongated WPBs. Nuclear magnetic resonance data showed that the higher pHi in hiPSC‐ECs occurred in association with decreased intracellular lactate concentrations. This was explained by decreased glycolytic flux toward pyruvate and lactate in hiPSC‐ECs. In addition, decreased expression of monocarboxylate transporter member 1, a member of the solute carrier family (SLC16A1), which regulates lactate and H+ uptake, contributed to the high pHi of hiPSC‐EC. Mechanistically, pro‐VWF dimers require the lower pH environment of the trans‐Golgi network for maturation and tubulation. These data show that while hiPSC‐ECs may share many features with mature EC, they are characterized by metabolic immaturity hampering proper EC function.<br />Formation of mature Weibel‐Palade bodies in human‐induced pluripotent stem cell‐derived endothelial cells is limited by the increased intracellular pH (pHi) around the Golgi apparatus and trans‐Golgi network. This increase in pHi is caused by reduced intracellular lactate accompanied by reduced H+, caused by reduced glycolysis, and reduced the uptake of lactate and H+ via monocarboxylate transporter member 1.
- Subjects :
- 0301 basic medicine
induced pluripotent stem cell‐derived endothelial cells
Angiogenesis
Cell- and Tissue-Based Therapy
von Willebrand factor
ANGIOGENESIS
0302 clinical medicine
HUMAN IPSCS
Weibel-Palade bodies
PLASTICITY
Induced pluripotent stem cell
Monocarboxylate transporter
lcsh:R5-920
biology
Chemistry
lcsh:Cytology
Cell Differentiation
General Medicine
glycolysis
Cell biology
Weibel‐Palade bodies
medicine.anatomical_structure
DIFFERENTIATION
SECRETION
lcsh:Medicine (General)
Life Sciences & Biomedicine
Intracellular
STORAGE
Endothelium
VON-WILLEBRAND-FACTOR
Intracellular pH
Induced Pluripotent Stem Cells
induced pluripotent stem cell-derived endothelial cells
METABOLISM
Transfection
03 medical and health sciences
Cell & Tissue Engineering
Tissue Engineering and Regenerative Medicine
Weibel–Palade body
medicine
Humans
lcsh:QH573-671
Science & Technology
Endothelial Cells
Cell Biology
030104 developmental biology
ANGIOPOIETIN-2
biology.protein
cell therapy
030217 neurology & neurosurgery
Homeostasis
Developmental Biology
GENERATION
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Stem Cells Translational Medicine, Stem Cells Translational Medicine, Vol 9, Iss 7, Pp 758-772 (2020), Stem Cells Translational Medicine, 9(7), 758-772. WILEY
- Accession number :
- edsair.doi.dedup.....3619da025088019ce74640e205cb5af7