In situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis

Choi, J.R. and Pingguan-Murphy, Belinda and Wan Abas, Wan Abu Bakar and Yong, K.W. and Poon, C.T. and Noor Azmi, Mat Adenan and Omar, Siti Zawiah and Chua, K.H. and Xu, F. and Wan Kamarul Zaman, Wan Safwani (2015) In situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis. PLoS ONE, 10 (1). e0115034. ISSN 1932-6203, DOI

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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 O-2 concentration (21 O-2) or in situ normoxia (2 O-2). 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 O-2 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 O-2 as an ideal culture condition for expanding ASCs efficiently while maintaining their characteristics.

Item Type: Article
Funders: University of Malaya, High Impact Research Grant from the Ministry of Higher Education Malaysia UM.C/HIR/MOHE/ENG/44, Major International Joint Research Program of China 11120101002 , National Natural Science Foundation of China 11372243 , National 111 Project of China B06024
Additional Information: Choi, Jane Ru Pingguan-Murphy, Belinda Wan Abas, Wan Abu Bakar Yong, Kar Wey Poon, Chi Tat Noor Azmi, Mat Adenan Omar, Siti Zawiah Chua, Kien Hui Xu, Feng Wan Safwani, Wan Kamarul Zaman eng Research Support, Non-U.S. Gov't 2015/01/24 06:00 PLoS One. 2015 Jan 23;10(1):e0115034. doi: 10.1371/journal.pone.0115034. eCollection 2015.
Subjects: T Technology > T Technology (General)
T Technology > TA Engineering (General). Civil engineering (General)
Divisions: Faculty of Engineering
Depositing User: Mr Jenal S
Date Deposited: 22 Sep 2015 01:06
Last Modified: 16 Dec 2019 03:38

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