title: Hypoxia-cultured human adipose-derived mesenchymal stem cells are non-oncogenic and have enhanced viability, motility, and tropism to brain cancer.
abstract: Adult human adipose-derived mesenchymal stem cells (hAMSCs) are multipotent cells, which are abundant, easily collected, and bypass the ethical concerns that plague embryonic stem cells. Their utility and accessibility have led to the rapid development of clinical investigations to explore their autologous and allogeneic cellular-based regenerative potential, tissue preservation capabilities, anti-inflammatory properties, and anticancer properties, among others. hAMSCs are typically cultured under ambient conditions with 21% oxygen. However, physiologically, hAMSCs exist in an environment of much lower oxygen tension. Furthermore, hAMSCs cultured in standard conditions have shown limited proliferative and migratory capabilities, as well as limited viability. This study investigated the effects hypoxic culture conditions have on primary intraoperatively derived hAMSCs. hAMSCs cultured under hypoxia (hAMSCs-H) remained multipotent, capable of differentiation into osteogenic, chondrogenic, and adipogenic lineages. In addition, hAMSCs-H grew faster and exhibited less cell death. Furthermore, hAMSCs-H had greater motility than normoxia-cultured hAMSCs and exhibited greater homing ability to glioblastoma (GBM) derived from brain tumor-initiating cells from our patients in vitro and in vivo. Importantly, hAMSCs-H did not transform into tumor-associated fibroblasts in vitro and were not tumorigenic in vivo. Rather, hAMSCs-H promoted the differentiation of brain cancer cells in vitro and in vivo. These findings suggest an alternative culturing technique that can enhance the function of hAMSCs, which may be necessary for their use in the treatment of various pathologies including stroke, myocardial infarction, amyotrophic lateral sclerosis, and GBM.
authors.affiliation: 1] Department of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA [2] Department of Pharmacology, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhengjiang, Jiangshu, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.affiliation: 1] Department of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA [2] Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: M
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Dangelmajer
authors.affiliation: Department of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Y M
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: O
authors.initials: O
authors.lastname: Wijesekera
authors.affiliation: Department of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: C X
authors.initials: CX
authors.lastname: Castellanos
authors.affiliation: Department of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Denduluri
authors.affiliation: Department of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Chaichana
authors.affiliation: Department of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Engineering and Applied Science, Yale University, New Haven, CT, USA.
authors.forename: A
authors.initials: A
authors.lastname: Levchenko
authors.affiliation: Department of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: H
authors.initials: H
authors.lastname: Guerrero-Cazares
authors.affiliation: Department of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Quiñones-Hinojosa
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D002454:Cell Differentiation; D015687:Cell Hypoxia; D002460:Cell Line; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008875:Middle Aged; D010100:Oxygen / Q000032:analysis / Q000378:metabolism*; D018523:Tropism
chemical_list: D010100:Oxygen