Three-dimensional spheroid formation of adipose-derived stem cells
improves the survival of fat transplantation by enhance their
therapeutic effect
Abstract
Adipose-derived stem cells (ADSCs) have important applications in basic
research, especially in fat transplantation. Some studies have found
that three-dimensional (3D) spheroids formed by mesenchymal stem cells
have enhanced therapeutic potential. However, the fundamental basics of
this effect are still being discussed. In this study, ADSCs were
harvested from subcutaneous adipose tissues and 3D spheroids were formed
by the automatic aggregation of ADSCs in a non-adhesive 6-well plate.
Oxygen glucose deprivation (OGD) was used to simulate the
transplantation microenvironment. We found that 3D culture of ADSCs
triggered cell autophagy. After inhibiting autophagy by Chloroquine, the
rates of apoptosis were increased. When the 3D ADSC-spheroids were
re-planked, the number of senescent ADSCs decreased, and the
proliferation ability was promoted. In addition, there were more
cytokines secreted by 3D ADSC-spheroids including VEGF, IGF-1 and TGF-β.
After adding the conditioned medium with human umbilical vein
endothelial cells (HUVECs), 3D ADSC-spheroids were more likely to
promote migration, and tube formation, stimulating the formation of new
blood vessels. Fat grafting experiments in nude mice also showed that 3D
ADSC-spheroids enhanced survival and neovascularization of fat grafts.
These results suggested that 3D spheroids culturing of ADSCs can
increase the therapeutic potential in fat transplantation.