Effects of Long-Term In Vitro Expansion on Genetic Stability and Tumor Formation Capacity of Stem Cells.

Autor: Nam H; Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Suwon, Gyeonggi-do, 16419, South Korea.; Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, 16419, South Korea.; Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, 06351, South Korea., Lee IH; Computational Health Informatics Program, Boston Children's Hospital, Boston, MA, 02115, USA., Sa JK; Department of Biomedical Sciences, Korea University College of Medicine, Seoul, South Korea., Kim SS; Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Suwon, Gyeonggi-do, 16419, South Korea.; Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, 16419, South Korea.; Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, 06351, South Korea.; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, South Korea., Pyeon HJ; Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Suwon, Gyeonggi-do, 16419, South Korea.; Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, 16419, South Korea.; Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, 06351, South Korea., Lee KH; Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Suwon, Gyeonggi-do, 16419, South Korea.; Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, 16419, South Korea.; Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, 06351, South Korea., Lee K; Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Suwon, Gyeonggi-do, 16419, South Korea.; Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, 16419, South Korea.; Biomedical Institute for Convergence at Sungkyunkwan University (BICS), Sungkyunkwan University, Suwon, 16419, South Korea., Lee SH; Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, 16419, South Korea. sobotta72@gmail.com.; Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, 06351, South Korea. sobotta72@gmail.com.; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, South Korea. sobotta72@gmail.com.; Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea. sobotta72@gmail.com., Joo KM; Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Suwon, Gyeonggi-do, 16419, South Korea. kmjoo@skku.edu.; Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, 16419, South Korea. kmjoo@skku.edu.; Stem Cell and Regenerative Medicine Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, 06351, South Korea. kmjoo@skku.edu.; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, South Korea. kmjoo@skku.edu.; Biomedical Institute for Convergence at Sungkyunkwan University (BICS), Sungkyunkwan University, Suwon, 16419, South Korea. kmjoo@skku.edu.
Jazyk: angličtina
Zdroj: Stem cell reviews and reports [Stem Cell Rev Rep] 2022 Jan; Vol. 18 (1), pp. 241-257. Date of Electronic Publication: 2021 Nov 04.
DOI: 10.1007/s12015-021-10290-z
Abstrakt: Stem cell therapeutics are emerging as novel alternative treatments for various neurodegenerative diseases based on their regenerative potentials. However, stem cell transplantation might have side effects such as tumor formation that limit their clinical applications. Especially, in vitro expansion of stem cells might provoke genetic instability and tumorigenic potential. To address this issue, we analyzed genomic alterations of adult human multipotent neural cells (ahMNCs), a type of human adult neural stem cells, after a long-term in vitro culture process (passage 15) using sensitive analysis techniques including karyotyping, array comparative genomic hybridization (aCGH), and whole exome sequencing (WES). Although karyotyping did not find any major abnormalities in chromosomal number or structure, diverse copy number variations (CNVs) and genetic mutations were detected by aCGH and WES in all five independent ahMNCs. However, the number of CNVs and genetic mutations did not increase and many of them did not persist as in vitro culture progressed. Although most observed CNVs and genetic mutations were not shared by all five ahMNCs, nonsynonymous missense mutations at MUC4 were found in three out of five long-term cultured ahMNC lines. The genetic instability did not confer in vivo tumorigenic potential to ahMNCs. Collectively, these results indicate that, although genetic instability can be induced by long-term in vitro expansion of stem cells, it is not sufficient to fully exert tumor formation capacity of stem cells. Other functional effects of such genetic instability need to be further elucidated.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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