Oxidative stress mediates depot-specific functional differences of human adipose-derived stem cells

Stem Cell Research & Therapy

Sue-Anne Toh¹  Min Park²  Asim Shabbir³  Chengxiang Yuan⁴  Sandhya Sriram⁴  Shigeki Sugii⁵  Winson Tay⁶  Smarajit Chakraborty⁶  Weiping Han⁷ 

[1] 0000 0001 2180 6431, grid.4280.e, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, 117599, Singapore, Singapore;0000 0004 0385 0924, grid.428397.3, Duke-NUS Medical School, 8 College Road, 169857, Singapore, Singapore;0000 0004 0621 9599, grid.412106.0, Department of Surgery, National University Hospital, 5 Lower Kent Ridge Road, 119074, Singapore, Singapore;0000 0004 0637 0221, grid.185448.4, Fat Metabolism and Stem Cell Group, Singapore Bioimaging Consortium (SBIC), Agency for Science, Technology and Research (A*STAR), 11 Biopolis Way #02-02, 138667, Singapore, Singapore;0000 0004 0637 0221, grid.185448.4, Fat Metabolism and Stem Cell Group, Singapore Bioimaging Consortium (SBIC), Agency for Science, Technology and Research (A*STAR), 11 Biopolis Way #02-02, 138667, Singapore, Singapore;0000 0004 0385 0924, grid.428397.3, Duke-NUS Medical School, 8 College Road, 169857, Singapore, Singapore;0000 0004 0637 0221, grid.185448.4, Present address: Institute of Bioengineering and Nanotechnology (IBN), Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way #07-01, 138669, Singapore, Singapore;0000 0004 0637 0221, grid.185448.4, Fat Metabolism and Stem Cell Group, Singapore Bioimaging Consortium (SBIC), Agency for Science, Technology and Research (A*STAR), 11 Biopolis Way #02-02, 138667, Singapore, Singapore;0000 0004 0637 0221, grid.185448.4, Present address: Institute of Bioengineering and Nanotechnology (IBN), Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way #07-01, 138669, Singapore, Singapore;0000 0004 0637 0221, grid.185448.4, Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium (SBIC), Agency for Science, Technology and Research (A*STAR), 11 Biopolis Way, 138667, Singapore, Singapore;

关键词: Subcutaneous fat;    Intra-abdominal fat;    Mesenchymal stromal cells;    Oxidative stress;    Reactive oxygen species;    Ascorbic acid;   

DOI  :  10.1186/s13287-019-1240-y

来源: publisher

【 摘 要 】

BackgroundVisceral (VS) fat depot is known to have defective adipogenic functions compared to subcutaneous (SC) fat, but its mechanism of origin is unclear.ObjectiveWe tested our hypothesis that the degree of oxidative stress in adipose-derived stem cells (ASCs) from these depots may account for this difference.MethodsASCs were isolated from VS (omental region) and SC (abdominal region) fat depots of human subjects undergoing bariatric surgery. ASCs from VS and SC fat were investigated for their cellular characteristics in reactive oxygen species (ROS), metabolism, gene expression, proliferation, senescence, migration, and adipocyte differentiation. ASCs were also treated with antioxidant ascorbic acid (vitamin C).ResultsWe found that human VS-derived ASCs exhibit excessive oxidative stress characterized by high reactive oxygen species (ROS), compared to SC-derived ASCs. Gene expression analyses indicate that the VS-ASCs exhibit higher levels of genes involved in pro-oxidant and pro-inflammatory pathways and lower levels of genes in antioxidant and anti-inflammatory pathways. VS-ASCs have impaired cellular functions compared to SC-ASCs, such as slower proliferation, early senescence, less migratory activity, and poor adipogenic capability in vitro. Treatment with ascorbic acid decreased ROS levels drastically in VS-ASCs. Ascorbic acid treatment substantially improved proliferation, senescence, migration, and adipogenic capacities of compromised ASCs caused by high ROS.ConclusionsThis finding suggests the fat depot-specific differences of cellular defects originating from stem cell population. Considering clinical potentials of human ASCs for cell therapies, this also offers a possible strategy for improving their therapeutic qualities through antioxidants.

【 授权许可】

CC BY