title: In situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis.
abstract: Adipose tissue-derived stromal cells (ASCs) natively reside in a relatively low-oxygen tension (i.e., hypoxic) microenvironment in human body. Low oxygen tension (i.e., in situ normoxia), has been known to enhance the growth and survival rate of ASCs, which, however, may lead to the risk of tumourigenesis. Here, we investigated the tumourigenic potential of ASCs under their physiological condition to ensure their safe use in regenerative therapy. Human ASCs isolated from subcutaneous fat were cultured in atmospheric O2 concentration (21% O2) or in situ normoxia (2% O2). We found that ASCs retained their surface markers, tri-lineage differentiation potential, and self-renewal properties under in situ normoxia without altering their morphology. In situ normoxia displayed a higher proliferation and viability of ASCs with less DNA damage as compared to atmospheric O2 concentration. Moreover, low oxygen tension significantly up-regulated VEGF and bFGF mRNA expression and protein secretion while reducing the expression level of tumour suppressor genes p16, p21, p53, and pRb. However, there were no significant differences in ASCs telomere length and their relative telomerase activity when cultured at different oxygen concentrations. Collectively, even with high proliferation and survival rate, ASCs have a low tendency of developing tumour under in situ normoxia. These results suggest 2% O2 as an ideal culture condition for expanding ASCs efficiently while maintaining their characteristics.
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
authors.forename: Jane Ru
authors.initials: JR
authors.lastname: Choi
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
authors.forename: Belinda
authors.initials: B
authors.lastname: Pingguan-Murphy
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
authors.forename: Wan Abu Bakar
authors.initials: WA
authors.lastname: Wan Abas
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
authors.forename: Kar Wey
authors.initials: KW
authors.lastname: Yong
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
authors.forename: Chi Tat
authors.initials: CT
authors.lastname: Poon
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
authors.forename: Mat Adenan
authors.initials: MA
authors.lastname: Noor Azmi
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
authors.forename: Siti Zawiah
authors.initials: SZ
authors.lastname: Omar
authors.affiliation: Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
authors.forename: Kien Hui
authors.initials: KH
authors.lastname: Chua
authors.affiliation: The Key Library of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, P.R. China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an 710049, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia.
authors.forename: Wan Kamarul Zaman
authors.initials: WK
authors.lastname: Wan Safwani
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000328:Adult; D063646:Carcinogenesis; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D010100:Oxygen / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism; D059505:Telomere Homeostasis; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D019098:Telomerase; D010100:Oxygen