Dataset Information

Effects of Propofol Treatment in Neural Progenitors Derived from Human-Induced Pluripotent Stem Cells.

ABSTRACT: Propofol is an intravenous anesthetic that has been widely used in clinics. Besides its anesthetic effects, propofol has also been reported to influence the regulation of the autonomic system. Controversies exist with regard to whether propofol exposure is safe for pregnant women and young children. In this work, human-induced pluripotent stem cell- (hiPSC-) derived neural progenitor cells (NPCs) were treated with propofol at 20, 50, 100, or 300??M for 6?h or 24?h, and acute and subacute cell injury, cell proliferation, and apoptosis were evaluated. Comparison of genome-wide gene expression profiles was performed for treated and control iPSC-NPCs. Propofol treatment for 6?h at the clinically relevant concentration (20 or 50??M) did not affect cell viability, apoptosis, or proliferation, while propofol at higher concentration (100 or 300??M) decreased NPC viability and induced apoptosis. In addition, 20??M propofol treatment for 6?h did not alter global gene expression. In summary, propofol treatment at commonly practiced clinical doses for 6?h did not have adverse effects on hiPSC-derived NPCs. In contrast, longer exposure and/or higher concentration could decrease NPC viability and induce apoptosis.

SUBMITTER: Long B

PROVIDER: S-EPMC5651106 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Effects of Propofol Treatment in Neural Progenitors Derived from Human-Induced Pluripotent Stem Cells.

Long Bo B Li Shenglan S Xue Haipeng H Sun Li L Kim Dong H DH Liu Ying Y

Neural plasticity 20171008

Propofol is an intravenous anesthetic that has been widely used in clinics. Besides its anesthetic effects, propofol has also been reported to influence the regulation of the autonomic system. Controversies exist with regard to whether propofol exposure is safe for pregnant women and young children. In this work, human-induced pluripotent stem cell- (hiPSC-) derived neural progenitor cells (NPCs) were treated with propofol at 20, 50, 100, or 300 <i>μ</i>M for 6 h or 24 h, and acute and subacute ...[more]

PMID: 29119024

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Project description:BackgroundHuman induced pluripotent stem cells (hiPSCs) offer a renewable source of cells for the generation of hematopoietic cells for cell-based therapy, disease modeling, and drug screening. However, current serum/feeder-free differentiation protocols rely on the use of various cytokines, which makes the process very costly or the generation of embryoid bodies (EBs), which are labor-intensive and can cause heterogeneity during differentiation. Here, we report a simple feeder and serum-free monolayer protocol for efficient generation of iPSC-derived multipotent hematoendothelial progenitors (HEPs), which can further differentiate into endothelial and hematopoietic cells including erythroid and T lineages.MethodsFormation of HEPs from iPSCs was initiated by inhibition of GSK3 signaling for 2 days followed by the addition of VEGF and FGF2 for 3 days. The HEPs were further induced toward mature endothelial cells (ECs) in an angiogenic condition and toward T cells by co-culturing with OP9-DL1 feeder cells. Endothelial-to-hematopoietic transition (EHT) of the HEPs was further promoted by supplementation with the TGF-β signaling inhibitor. Erythroid differentiation was performed by culturing the hematopoietic stem/progenitor cells (HSPCs) in a three-stage erythroid liquid culture system.ResultsOur protocol significantly enhanced the number of KDR+ CD34+ CD31+ HEPs on day 5 of differentiation. Further culture of HEPs in angiogenic conditions promoted the formation of mature ECs, which expressed CD34, CD31, CD144, vWF, and ICAM-1, and could exhibit the formation of vascular-like network and acetylated low-density lipoprotein (Ac-LDL) uptake. In addition, the HEPs were differentiated into CD8+ T lymphocytes, which could be expanded up to 34-fold upon TCR stimulation. Inhibition of TGF-β signaling at the HEP stage promoted EHT and yielded a large number of HSPCs expressing CD34 and CD43. Upon erythroid differentiation, these HSPCs were expanded up to 40-fold and displayed morphological changes following stages of erythroid development.ConclusionThis protocol offers an efficient and simple approach for the generation of multipotent HEPs and could be adapted to generate desired blood cells in large numbers for applications in basic research including developmental study, disease modeling, and drug screening as well as in regenerative medicine.

Dataset Information

Effects of Propofol Treatment in Neural Progenitors Derived from Human-Induced Pluripotent Stem Cells.

Publications

Effects of Propofol Treatment in Neural Progenitors Derived from Human-Induced Pluripotent Stem Cells.

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