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Diverse effects of dimethyl sulfoxide (DMSO) on the differentiation potential of human embryonic stem cells.
Arch Toxicol. 2012 Apr; 86(4):651-61.AT

Abstract

In vitro disease modeling using pluripotent stem cells can be a fast track screening tool for toxicological testing of candidate drug molecules. Dimethyl sulfoxide (DMSO) is one of the most commonly used solvents in drug screening. In the present investigation, we exposed 14- to 21-day-old embryoid bodies (EBs) to three different concentrations of DMSO [0.01% (low dose), 0.1% (medium dose) and 1.0% (high dose)] to identify the safest dose that could effectively be used as solvent. We found that DMSO treatment substantially altered the morphology and attachment of cells in concurrence with a significant reduction in cell viability in a dose-dependent manner. Gene expression studies revealed a selective downregulation of key markers associated with stemness (Oct-4, Sox-2, Nanog and Rex-1); ectoderm (Nestin, TuJ1, NEFH and Keratin-15); mesoderm (HAND-1, MEF-2C, GATA-4 and cardiac-actin); and endoderm (SOX-17, HNF-3β, GATA-6 and albumin), indicating an aberrant and untimely differentiation trajectory. Furthermore, immunocytochemistry, flow cytometry and histological analyses demonstrated substantial decrease in the levels of albumin and CK-18 proteins coupled with a massive reduction in the number of cells positive for PAS staining, implicating reduced deposits of glycogen. Our study advocates for the first time that DMSO exposure not only affects the phenotypic characteristics but also induces significant alteration in gene expression, protein content and functionality of the differentiated hepatic cells. Overall, our experiments warrant that hESC-based assays can provide timely alerts about the outcome of widespread applications of DMSO as drug solvent, cryoprotectant and differentiating agent.

Authors+Show Affiliations

Manipal Institute of Regenerative Medicine, Manipal University Branch Campus, Bangalore, India.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22105179

Citation

Pal, Rajarshi, et al. "Diverse Effects of Dimethyl Sulfoxide (DMSO) On the Differentiation Potential of Human Embryonic Stem Cells." Archives of Toxicology, vol. 86, no. 4, 2012, pp. 651-61.
Pal R, Mamidi MK, Das AK, et al. Diverse effects of dimethyl sulfoxide (DMSO) on the differentiation potential of human embryonic stem cells. Arch Toxicol. 2012;86(4):651-61.
Pal, R., Mamidi, M. K., Das, A. K., & Bhonde, R. (2012). Diverse effects of dimethyl sulfoxide (DMSO) on the differentiation potential of human embryonic stem cells. Archives of Toxicology, 86(4), 651-61. https://doi.org/10.1007/s00204-011-0782-2
Pal R, et al. Diverse Effects of Dimethyl Sulfoxide (DMSO) On the Differentiation Potential of Human Embryonic Stem Cells. Arch Toxicol. 2012;86(4):651-61. PubMed PMID: 22105179.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diverse effects of dimethyl sulfoxide (DMSO) on the differentiation potential of human embryonic stem cells. AU - Pal,Rajarshi, AU - Mamidi,Murali Krishna, AU - Das,Anjan Kumar, AU - Bhonde,Ramesh, Y1 - 2011/11/22/ PY - 2011/10/14/received PY - 2011/11/10/accepted PY - 2011/11/23/entrez PY - 2011/11/23/pubmed PY - 2012/7/11/medline SP - 651 EP - 61 JF - Archives of toxicology JO - Arch Toxicol VL - 86 IS - 4 N2 - In vitro disease modeling using pluripotent stem cells can be a fast track screening tool for toxicological testing of candidate drug molecules. Dimethyl sulfoxide (DMSO) is one of the most commonly used solvents in drug screening. In the present investigation, we exposed 14- to 21-day-old embryoid bodies (EBs) to three different concentrations of DMSO [0.01% (low dose), 0.1% (medium dose) and 1.0% (high dose)] to identify the safest dose that could effectively be used as solvent. We found that DMSO treatment substantially altered the morphology and attachment of cells in concurrence with a significant reduction in cell viability in a dose-dependent manner. Gene expression studies revealed a selective downregulation of key markers associated with stemness (Oct-4, Sox-2, Nanog and Rex-1); ectoderm (Nestin, TuJ1, NEFH and Keratin-15); mesoderm (HAND-1, MEF-2C, GATA-4 and cardiac-actin); and endoderm (SOX-17, HNF-3β, GATA-6 and albumin), indicating an aberrant and untimely differentiation trajectory. Furthermore, immunocytochemistry, flow cytometry and histological analyses demonstrated substantial decrease in the levels of albumin and CK-18 proteins coupled with a massive reduction in the number of cells positive for PAS staining, implicating reduced deposits of glycogen. Our study advocates for the first time that DMSO exposure not only affects the phenotypic characteristics but also induces significant alteration in gene expression, protein content and functionality of the differentiated hepatic cells. Overall, our experiments warrant that hESC-based assays can provide timely alerts about the outcome of widespread applications of DMSO as drug solvent, cryoprotectant and differentiating agent. SN - 1432-0738 UR - https://www.unboundmedicine.com/medline/citation/22105179/Diverse_effects_of_dimethyl_sulfoxide__DMSO__on_the_differentiation_potential_of_human_embryonic_stem_cells_ L2 - https://doi.org/10.1007/s00204-011-0782-2 DB - PRIME DP - Unbound Medicine ER -