Mesenchymal Stem/Stromal Cells Derived From a Reproductive Tissue Niche Under Oxidative Stress Have High Aldehyde Dehydrogenase Activity
- 383 Downloads
The use of mesenchymal stem/stromal cells (MSC) in regenerative medicine often requires MSC to function in environments of high oxidative stress. Human pregnancy is a condition where the mother’s tissues, and in particular her circulatory system, are exposed to increased levels of oxidative stress. MSC in the maternal decidua basalis (DMSC) are in a vascular niche, and thus would be exposed to oxidative stress products in the maternal circulation. Aldehyde dehydrogenases (ALDH) are a large family of enzymes which detoxify aldehydes and thereby protect stem cells against oxidative damage. A subpopulation of MSC express high levels of ALDH (ALDHbr) and these are more potent in repairing and regenerating tissues. DMSC was compared with chorionic villous MSC (CMSC) derived from the human placenta. CMSC reside in vascular niche and are exposed to the fetal circulation, which is in lower oxidative state. We screened an ALDH isozyme cDNA array and determined that relative to CMSC, DMSC expressed high levels of ALDH1 family members, predominantly ALDH1A1. Immunocytochemistry gave qualitative confirmation at the protein level. Immunofluorescence detected ALDH1 immunoreactivity in the DMSC and CMSC vascular niche. The percentage of ALDHbr cells was calculated by Aldefluor assay and DMSC showed a significantly higher percentage of ALDHbr cells than CMSC. Finally, flow sorted ALDHbr cells were functionally potent in colony forming unit assays. DMSC, which are derived from pregnancy tissues that are naturally exposed to high levels of oxidative stress, may be better candidates for regenerative therapies where MSC must function in high oxidative stress environments.
KeywordsMesenchymal stem cells Chorionic villi Decidua Placenta Aldehyde dehydrogenase
The authors wish to thank the clinical research midwives, Sue Duggan and Moira Stewart, for patient sample collection at the Royal Women’s Hospital. We also thank Dr. Matthew Burton for his advice with flow cytometry gating, Melissa Duggan and Debora Singgih for their technical assistance. Financial support was provided by research funding from King Abdullah International Medical Research Centre (Grant No. RC08/114), the Royal Women’s Hospital Foundation, and an Australian Stem Cell Centre Postgraduate Scholarship.
- 9.Ashok, A., A. Nabil, & Botros, R. (2013). Studies on Women's Health. Oxidative Stress in Applied Basic Research and Clinical Practice ed. N.A. Ashok Agarwal, Botros Rizk, New York: Humana Press.Google Scholar
- 11.Kusuma, G.D., et al., (2015). Mesenchymal stem cells reside in a vascular niche in the decidua basalis and are absent in remodelled spiral arterioles. Placenta.Google Scholar
- 13.Poston, L. and M.T. Raijmakers( 2004). Trophoblast oxidative stress, antioxidants and pregnancy outcome–a review. Placenta, 25 Suppl A: p. S72-8.Google Scholar
- 16.Jackson, B., et al. (2011). Update on the aldehyde dehydrogenase gene (ALDH) superfamily. Human Genomics, 5(4), 283–303.Google Scholar
- 19.Guppy, N., L. Nicholson, and Alison, M. (2011). ABC Transporters, Aldehyde Dehydrogenase, and Adult Stem Cells, in Adult Stem Cells, D.G. Phinney, Editor. Humana Press. p. 181-199.Google Scholar
- 23.Chen, Y., et al. (2012). Focus on molecules: ALDH1A1: from lens and corneal crystallin to stem cell marker. Experimental Eye Research,. 102(0): p. 105–106.Google Scholar
- 26.Singh, S., et al., Aldehyde dehydrogenases in cellular responses to oxidative/electrophilic stress. Free Radical Biology & Medicine, 2013. 56(0): p. 89–101.Google Scholar
- 31.Qin, S. Q., et al. (2016) Establishment and characterization of fetal and maternal mesenchymal stem/stromal cell lines from the human term placenta. Placenta. doi: 10.1016/j.placenta.2016.01.018.
- 42.Penumatsa, K., et al., (2010) Differential expression of aldehyde dehydrogenase 1a1 (ALDH1) in normal ovary and serous ovarian tumors. J Ovarian Res,. 3: p. 28.Google Scholar
- 53.Hess, D. A., et al. (2008). Widespread nonhematopoietic tissue distribution by transplanted human progenitor cells with high aldehyde dehydrogenase activity. Stem Cells, 26(3), 611c620.Google Scholar