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

Jane Ru Choi, Belinda Pingguan-Murphy, Wan Abu Bakar Wan Abas, Kar Wey Yong, Chi Tat Poon, Adenan Noor Azmi, Siti Zawiah Omar, Chua Kien Hui, Feng Xu, Wan Kamarul Zaman Wan Safwani

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish
Article numbere0115034
JournalPLoS One
Volume10
Issue number1
DOIs
Publication statusPublished - 23 Jan 2015

Fingerprint

normoxia
stromal cells
Stromal Cells
adipose tissue
Adipose Tissue
Survival Rate
Tissue
Oxygen
oxygen
Tumors
survival rate
telomerase
protein secretion
tumor suppressor genes
Subcutaneous Fat
Telomerase
telomeres
Telomere
subcutaneous fat
Tumor Suppressor Genes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Choi, J. R., Pingguan-Murphy, B., Abas, W. A. B. W., Yong, K. W., Poon, C. T., Azmi, A. N., ... Safwani, W. K. Z. W. (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]. https://doi.org/10.1371/journal.pone.0115034

In situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis. / Choi, Jane Ru; Pingguan-Murphy, Belinda; Abas, Wan Abu Bakar Wan; Yong, Kar Wey; Poon, Chi Tat; Azmi, Adenan Noor; Omar, Siti Zawiah; Kien Hui, Chua; Xu, Feng; Safwani, Wan Kamarul Zaman Wan.

In: PLoS One, Vol. 10, No. 1, e0115034, 23.01.2015.

Research output: Contribution to journalArticle

Choi, Jane Ru ; Pingguan-Murphy, Belinda ; Abas, Wan Abu Bakar Wan ; Yong, Kar Wey ; Poon, Chi Tat ; Azmi, Adenan Noor ; Omar, Siti Zawiah ; Kien Hui, Chua ; Xu, Feng ; Safwani, Wan Kamarul Zaman Wan. / In situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis. In: PLoS One. 2015 ; Vol. 10, No. 1.
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