Sriram, S., Yuan, C., Chakraborty, S. et al. Oxidative stress mediates depot-specific functional differences of human adipose-derived stem cells. Stem Cell Res Ther 10, 141 (2019). https://doi.org/10.1186/s13287-019-1240-y
Visceral (VS) fat depot is known to have defective adipogenic functions compared to subcutaneous (SC) fat, but its mechanism of origin is unclear.
We tested our hypothesis that the degree of oxidative stress in adipose-derived stem cells (ASCs) from these depots may account for this difference.
ASCs 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).
We 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.
This 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.
This work was supported by intramural funding from Biomedical Research Council of Agency for Science, Technology and Research (A*STAR) to Sh. Su, Singapore-China Joint Grant Project #1412424003 to Sh. Su and M.P, Developmental Programme Grant (#1334k00083) from A*STAR Joint Council Office to Sa.Sr and Sh.Su, and funding from the Singapore National Medical Research Council (NMRC) to S-A.T.