Author:
Sun Li-Yi,Pang Cheng-Yoong,Li Dian-Kun,Liao Chia-Hsin,Huang Wei-Chao,Wu Chao-Chuan,Chou Yi-Yo,Li Wei Wu,Chen Shin-Yuan,Liu Hwan-Wun,Chang Yao-Jen,Cheng Ching-Feng
Abstract
Abstract
Background
Antioxidants have been shown to enhance the proliferation of adipose-derived mesenchymal stem cells (ADMSCs) in vitro, although the detailed mechanism(s) and potential side effects are not fully understood.
In this study, human ADMSCs cultured in ImF-A medium supplemented with antioxidants (N-acetyl-l-cysteine and ascorbic acid-2-phosphate) and fibroblast growth factor 2 (FGF-2) were compared with ADMSCs cultured with FGF-2 alone (ImF) or with FGF-2 under 5% pO2 conditions (ImF-H).
Results
During log-phase growth, exposure to ImF-A resulted in a higher percentage of ADMSCs in the S phase of the cell cycle and a smaller percentage in G0/G1 phase. This resulted in a significantly reduced cell-doubling time and increased number of cells in the antioxidant-supplemented cultures compared with those supplemented with FGF-2 alone, an approximately 225% higher cell density after 7 days. Western blotting showed that the levels of the CDK inhibitors p21 and p27 decreased after ImF-A treatment, whereas CDK2, CDK4, and CDC2 levels clearly increased. In addition, ImF-A resulted in significant reduction in the expression of CD29, CD90, and CD105, whereas relative telomere length, osteogenesis, adipogenesis, and chondrogenesis were enhanced. The results were similar for ADMSCs treated with antioxidants and those under hypoxic conditions.
Conclusion
Antioxidant treatment promotes entry of ADMSCs into the S phase by suppressing cyclin-dependent kinase inhibitors and results in rapid cell proliferation similar to that observed under hypoxic conditions.
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Biochemistry (medical),Cell Biology,Clinical Biochemistry,Molecular Biology,General Medicine,Endocrinology, Diabetes and Metabolism
Reference41 articles.
1. Yao Y, Zhang F, Wang L, Zhang G, Wang Z, Chen J, Gao X: Lipopolysaccharide preconditioning enhances the efficacy of mesenchymal stem cells transplantation in a rat model of acute myocardial infarction. J Biomed Sci. 2009, 16: 74-10.1186/1423-0127-16-74.
2. Liu AM, Lu G, Tsang KS, Li G, Wu Y, Huang ZS, Ng HK, Kung HF, Poon WS: Umbilical cord-derived mesenchymal stem cells with forced expression of hepatocyte growth factor enhance remyelination and functional recovery in a rat intracerebral hemorrhage model. Neurosurgery. 2010, 67: 357-365. 10.1227/01.NEU.0000371983.06278.B3. discussion 365-356
3. Wong VW, Rustad KC, Glotzbach JP, Sorkin M, Inayathullah M, Major MR, Longaker MT, Rajadas J, Gurtner GC: Pullulan hydrogels improve mesenchymal stem cell delivery into high-oxidative-stress wounds. Macromol Biosci. 2011, 11: 1458-1466.
4. Ulloa-Montoya F, Verfaillie CM, Hu WS: Culture systems for pluripotent stem cells. J Biosci Bioeng. 2005, 100: 12-27. 10.1263/jbb.100.12.
5. King JA, Miller WM: Bioreactor development for stem cell expansion and controlled differentiation. Curr Opin Chem Biol. 2007, 11: 394-398. 10.1016/j.cbpa.2007.05.034.
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