J Ge1, H Cai, W S Tan. 1. The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
Abstract
OBJECTIVES: Ex vivo expansion is a feasible strategy, which may overcome limitation of the very low frequency of haematopoietic stem/progenitor cells, in umbilical cord blood (UCB). However, both quality of cells and safety of expanded population are critical issues to be addressed for their clinical application. Hence, in this study, we evaluated genetic stability of UCB-derived CD34(+) cells during ex vivo culture, based on karyotype analysis, as well as its effect on cell proliferation characteristics. MATERIALS AND METHODS: CD34(+) cells were isolated from human UCB samples by immunomagnetic separation and were expanded ex vivo over a 28-day period. Expansion of total nucleate cells, CD34(+) cells and CD34(+) CD38(-) cells was investigated. Karyotype analysis of the expanded cells from six randomly selected UCB samples was performed to evaluate their genetic stability. RESULTS: Chromosomal abnormality of expanded cells mainly appeared by day 14, but was seldom sustained until day 28. None of the chromosomal abnormal samples displayed neoplastic proliferation, and expanded cells with altered chromosomes did not show obvious transformation phenomena according to soft agar assay. CONCLUSIONS: Ex vivo expansion could lead to occurrence of chromosomal abnormality, although here it did not produce excessive proliferative advantage of the expended cells. Importantly, chromosomal alteration seemed not to be inheritable and unlikely to result in malignant transformation. However, further in-depth evaluation of potential clinical risks of chromosomal abnormality is warranted.
OBJECTIVES: Ex vivo expansion is a feasible strategy, which may overcome limitation of the very low frequency of haematopoietic stem/progenitor cells, in umbilical cord blood (UCB). However, both quality of cells and safety of expanded population are critical issues to be addressed for their clinical application. Hence, in this study, we evaluated genetic stability of UCB-derived CD34(+) cells during ex vivo culture, based on karyotype analysis, as well as its effect on cell proliferation characteristics. MATERIALS AND METHODS:CD34(+) cells were isolated from human UCB samples by immunomagnetic separation and were expanded ex vivo over a 28-day period. Expansion of total nucleate cells, CD34(+) cells and CD34(+) CD38(-) cells was investigated. Karyotype analysis of the expanded cells from six randomly selected UCB samples was performed to evaluate their genetic stability. RESULTS:Chromosomal abnormality of expanded cells mainly appeared by day 14, but was seldom sustained until day 28. None of the chromosomal abnormal samples displayed neoplastic proliferation, and expanded cells with altered chromosomes did not show obvious transformation phenomena according to soft agar assay. CONCLUSIONS: Ex vivo expansion could lead to occurrence of chromosomal abnormality, although here it did not produce excessive proliferative advantage of the expended cells. Importantly, chromosomal alteration seemed not to be inheritable and unlikely to result in malignant transformation. However, further in-depth evaluation of potential clinical risks of chromosomal abnormality is warranted.
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