The stability of in vitro cell cultures is an important issue for any clinical, bio-industrial, or pharmacological use. Embryonic stem cells are pluripotent; consequently, they possess the ability to differentiate into all three germ layers and are inherently prone to respond to differentiation stimuli. However, long-term culture inevitably yields clones that are best adapted to the culture conditions, passaging regimes, or differentiation sensitivity. This cellular plasticity is a major obstacle in the development of bio-industrial or clinical-grade cultures. At present, the quality control of cell cultures is limited by the lack of reliable (epi)genetic or molecular markers or by the focus on a particular type of instability such as karyotype abnormalities or adverse phenotypic traits. Therefore, there is an ongoing need for robust, feasible, and sensitive methods of determining or confirming cell status and for revealing potential divergences from the optimal state. We modeled both intrinsic and extrinsic changes in human embryonic stem cell (hESC) states using different experimental strategies and addressed the changes in cell status by intact cell mass spectrometry fingerprinting. The analysis of spectral fingerprints by methods routinely used in analytical chemistry clearly distinguished the morphologically and biochemically similar populations of hESCs and provided a biomarker-independent tool for the quality control of cell culture. Stem Cells Translational Medicine 2018;7:109-114.

Departamento de Química Unidad Departamental de Química Analítica Facultad de Ciencias Universidad de La Laguna Avda Astrofísico Fco Sánchez s n 38206 La Laguna Spain

Faculty of Medicine Department of Histology and Embryology Masaryk University Brno Czech Republic

Faculty of Science Department of Chemistry Masaryk University Brno Czech Republic

International Clinical Research Center St Anne's University Hospital Brno Czech Republic

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