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Mesenchymal Stem/Stromal Cells Derived From a Reproductive Tissue Niche Under Oxidative Stress Have High Aldehyde Dehydrogenase Activity

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Abstract

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.

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Acknowledgments

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.

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Correspondence to Bill Kalionis.

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Kusuma, G.D., Abumaree, M.H., Pertile, M.D. et al. Mesenchymal Stem/Stromal Cells Derived From a Reproductive Tissue Niche Under Oxidative Stress Have High Aldehyde Dehydrogenase Activity. Stem Cell Rev and Rep 12, 285–297 (2016). https://doi.org/10.1007/s12015-016-9649-5

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