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

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 tumourig...

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Main Authors: Choi, J.R., Pingguan-Murphy, Belinda, Wan Abas, Wan Abu Bakar, Yong, K.W., Poon, C.T., Noor Azmi, Mat Adenan, Omar, Siti Zawiah, Chua, K.H., Xu, F., Wan Kamarul Zaman, Wan Safwani
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Published: Public Library of Science 2015
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Online Access:http://eprints.um.edu.my/14049/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4304807/
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author Choi, J.R.
Pingguan-Murphy, Belinda
Wan Abas, Wan Abu Bakar
Yong, K.W.
Poon, C.T.
Noor Azmi, Mat Adenan
Omar, Siti Zawiah
Chua, K.H.
Xu, F.
Wan Kamarul Zaman, Wan Safwani
author_facet Choi, J.R.
Pingguan-Murphy, Belinda
Wan Abas, Wan Abu Bakar
Yong, K.W.
Poon, C.T.
Noor Azmi, Mat Adenan
Omar, Siti Zawiah
Chua, K.H.
Xu, F.
Wan Kamarul Zaman, Wan Safwani
author_sort Choi, J.R.
building UM Library
collection Institutional Repository
content_provider Universiti Malaya
content_source UM Research Repository
continent Asia
country Malaysia
description 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.
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spelling my.um.eprints-140492019-12-16T03:38:02Z http://eprints.um.edu.my/14049/ In situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis Choi, J.R. Pingguan-Murphy, Belinda Wan Abas, Wan Abu Bakar Yong, K.W. Poon, C.T. Noor Azmi, Mat Adenan Omar, Siti Zawiah Chua, K.H. Xu, F. Wan Kamarul Zaman, Wan Safwani T Technology (General) TA Engineering (General). Civil engineering (General) 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. Public Library of Science 2015-01-23 Article PeerReviewed 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 https://doi.org/10.1371/journal.pone.0115034 <https://doi.org/10.1371/journal.pone.0115034>. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4304807/ 10.1371/journal.pone.0115034
spellingShingle T Technology (General)
TA Engineering (General). Civil engineering (General)
Choi, J.R.
Pingguan-Murphy, Belinda
Wan Abas, Wan Abu Bakar
Yong, K.W.
Poon, C.T.
Noor Azmi, Mat Adenan
Omar, Siti Zawiah
Chua, K.H.
Xu, F.
Wan Kamarul Zaman, Wan Safwani
In situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis
title In situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis
title_full In situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis
title_fullStr In situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis
title_full_unstemmed In situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis
title_short In situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis
title_sort in situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis
topic T Technology (General)
TA Engineering (General). Civil engineering (General)
url http://eprints.um.edu.my/14049/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4304807/
url_provider http://eprints.um.edu.my/