PMID- 25019198 OWN - NLM STAT- MEDLINE DCOM- 20150916 LR - 20211021 IS - 1557-8534 (Electronic) IS - 1547-3287 (Print) IS - 1547-3287 (Linking) VI - 24 IP - 1 DP - 2015 Jan 1 TI - Asymmetric aneuploidy in mesenchymal stromal cells detected by in situ karyotyping and fluorescence in situ hybridization: suggestions for reference values for stem cells. PG - 77-92 LID - 10.1089/scd.2014.0137 [doi] AB - Cytogenetic testing is important to ensure patient safety before therapeutic application of mesenchymal stromal cells (MSCs). However, the standardized methods and criteria for the screening of chromosomal abnormalities of MSCs have not yet been determined. We investigated the frequency of cytogenetic aberrations in MSCs using G-banding and fluorescence in situ hybridization (FISH) and suggest reference values for aneuploidy in MSCs. Cytogenetic analysis was performed on 103 consecutive cultures from 68 MSCs (25 adipose-origin, 20 bone marrow-origin, 18 cord blood-origin, and 5 neural stem cells; 8 from adipose tissue of patients with breast cancer and 60 from healthy donors). We compared the MSC aneuploidy patterns with those of hematological malignancies and benign hematological diseases. Interphase FISH showed variable aneuploid clone proportions (1%-20%) in 68 MSCs. The aneuploidy patterns were asymmetric, and aneuploidy of chromosomes 16, 17, 18, and X occurred most frequently. Clones with polysomy were significantly more abundant than those with monosomy. The cutoff value of maximum polysomy rates (upper 95th percentile value) was 13.0%. By G-banding, 5 of the 61 MSCs presented clonal chromosomal aberrations. Aneuploidy was asymmetric in the malignant hematological diseases, while it was symmetric in the benign hematological diseases. We suggest an aneuploidy cutoff value of 13%, and FISH for aneuploidy of chromosomes 16, 17, 18, and X would be informative to evaluate the genetic stability of MSCs. Although it is unclear whether the aneuploid clones might represent the senescent cell population or transformed cells, more attention should be focused on the safety of MSCs, and G-banding combined with FISH should be performed. FAU - Kim, Seon Young AU - Kim SY AD - 1 Department of Laboratory Medicine, Seoul National University College of Medicine , Seoul, Republic of Korea. FAU - Im, Kyongok AU - Im K FAU - Park, Si Nae AU - Park SN FAU - Kwon, Jiseok AU - Kwon J FAU - Kim, Jung-Ah AU - Kim JA FAU - Choi, Qute AU - Choi Q FAU - Hwang, Sang Mee AU - Hwang SM FAU - Han, Sung-Hee AU - Han SH FAU - Kwon, Sunghoon AU - Kwon S FAU - Oh, Il-Hoan AU - Oh IH FAU - Lee, Dong Soon AU - Lee DS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Stem Cells Dev JT - Stem cells and development JID - 101197107 SB - IM MH - *Aneuploidy MH - *Chromosome Banding MH - Hematologic Neoplasms/metabolism/*pathology MH - Humans MH - In Situ Hybridization, Fluorescence MH - *Karyotyping MH - Mesenchymal Stem Cells/metabolism/*pathology PMC - PMC4273192 EDAT- 2014/07/16 06:00 MHDA- 2015/09/17 06:00 PMCR- 2016/01/01 CRDT- 2014/07/15 06:00 PHST- 2014/07/15 06:00 [entrez] PHST- 2014/07/16 06:00 [pubmed] PHST- 2015/09/17 06:00 [medline] PHST- 2016/01/01 00:00 [pmc-release] AID - 10.1089/scd.2014.0137 [pii] AID - 10.1089/scd.2014.0137 [doi] PST - ppublish SO - Stem Cells Dev. 2015 Jan 1;24(1):77-92. doi: 10.1089/scd.2014.0137.