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Open AccessArticle

Sphere-Forming Culture for Expanding Genetically Distinct Patient-Derived Glioma Stem Cells by Cellular Growth Rate Screening

1
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul 06531, Korea
2
Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Korea
3
Precision Medicine Research Institute, Samsung Medical Center, Seoul 06351, Korea
4
Graduate School of Biomedical Science, Ajou University School of Medicine, Suwon 16499, Korea
5
Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06531, Korea
6
Department of Hospital Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2020, 12(3), 549; https://doi.org/10.3390/cancers12030549
Received: 25 November 2019 / Revised: 21 February 2020 / Accepted: 25 February 2020 / Published: 27 February 2020
Diffusely infiltrating gliomas (DIGs) are difficult to completely resect and are associated with a high rate of tumor relapse and progression from low- to high-grade glioma. In particular, optimized short-term culture-enriching patient-derived glioma stem cells (GSCs) are essential for customizing the therapeutic strategy based on clinically feasible in vitro drug screening for a wide range of DIGs, owing to the high inter-tumoral heterogeneity. Herein, we constructed a novel high-throughput culture condition screening platform called ‘GFSCAN’, which evaluated the cellular growth rates of GSCs for each DIG sample in 132 serum-free combinations, using 13 previously reported growth factors closely associated with glioma aggressiveness. In total, 72 patient-derived GSCs with available genomic profiles were tested in GFSCAN to explore the association between cellular growth rates in specific growth factor combinations and genomic/molecular backgrounds, including isocitrate dehydrogenase 1 (IDH1) mutation, chromosome arm 1p and 19q co-deletion, ATRX chromatin remodeler alteration, and transcriptional subtype. GSCs were clustered according to the dependency on epidermal growth factor and basic fibroblast growth factor (E&F), and isocitrate dehydrogenase 1 (IDH1) wild-type GSCs showed higher E&F dependencies than IDH1 mutant GSCs. More importantly, we elucidated optimal combinations for IDH1 mutant glioblastoma and lower grade glioma GSCs with low dependencies on E&F, which could be an aid in clinical decision-making for these DIGs. Thus, we demonstrated the utility of GFSCAN in personalizing in vitro cultivation to nominate personalized therapeutic options, in a clinically relevant time frame, for individual DIG patients, where standard clinical options have been exhausted. View Full-Text
Keywords: diffuse infiltrating glioma; personalized medicine; glioma stem cells; short-term cultivation screening platform; growth factor; genomic profiling diffuse infiltrating glioma; personalized medicine; glioma stem cells; short-term cultivation screening platform; growth factor; genomic profiling
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MDPI and ACS Style

Shin, K.; Shin, H.; Cho, H.J.; Kang, H.; Lee, J.-K.; Seo, Y.J.; Shin, Y.J.; Kim, D.; Koo, H.; Kong, D.-S.; Seol, H.J.; Lee, J.-I.; Lee, H.W.; Nam, D.-H. Sphere-Forming Culture for Expanding Genetically Distinct Patient-Derived Glioma Stem Cells by Cellular Growth Rate Screening. Cancers 2020, 12, 549. https://doi.org/10.3390/cancers12030549

AMA Style

Shin K, Shin H, Cho HJ, Kang H, Lee J-K, Seo YJ, Shin YJ, Kim D, Koo H, Kong D-S, Seol HJ, Lee J-I, Lee HW, Nam D-H. Sphere-Forming Culture for Expanding Genetically Distinct Patient-Derived Glioma Stem Cells by Cellular Growth Rate Screening. Cancers. 2020; 12(3):549. https://doi.org/10.3390/cancers12030549

Chicago/Turabian Style

Shin, Kayoung; Shin, Hyemi; Cho, Hee J.; Kang, Hyunju; Lee, Jin-Ku; Seo, Yun J.; Shin, Yong J.; Kim, Donggeon; Koo, Harim; Kong, Doo-Sik; Seol, Ho J.; Lee, Jung-Il; Lee, Hye W.; Nam, Do-Hyun. 2020. "Sphere-Forming Culture for Expanding Genetically Distinct Patient-Derived Glioma Stem Cells by Cellular Growth Rate Screening" Cancers 12, no. 3: 549. https://doi.org/10.3390/cancers12030549

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