Use of BAC array CGH for evaluation of chromosomal stability of clinically used human mesenchymal stem cells and of cancer cell lines.

Abstract

Array-based comparative genomic hybridization (aCGH) using bacterial artificial chromosomes (BAC) is a powerful method to analyze DNA copy number aberrations of the entire human genome. In fact, CGH and aCGH have revealed various DNA copy number aberrations in numerous cancer cells and cancer cell lines examined so far. In this report, BAC aCGH was applied to evaluate the stability or instability of cell lines. Established cell lines have greatly contributed to advancements in not only biology but also medical science. However, cell lines have serious problems, such as alteration of biological properties during long-term cultivation. Firstly, we investigated two cancer cell lines, HeLa and Caco-2. HeLa cells, established from a cervical cancer, showed significantly increased DNA copy number alterations with passage time. Caco-2 cells, established from a colon cancer, showed no remarkable differences under various culture conditions. These results indicate that BAC aCGH can be used for the evaluation and validation of genomic stability of cultured cells. Secondly, BAC aCGH was applied to evaluate and validate the genomic stabilities of three patient's mesenchymal stem cells (MSCs), which were already used for their treatments. These three MSCs showed no significant differences in DNA copy number aberrations over their entire chromosomal regions. Therefore, BAC aCGH is highly recommended for use for a quality check of various cells before using them for any kind of biological investigation or clinical application.