BackgroundIncreased apoptosis in adipose tissue-derived stem cells (ADSCs) limits their application in treating diabetes complications. Autophagy is a molecular process that allows cells to degrade and recover damaged macromolecules, and closely interacts with apoptosis. The aim of the present study was to investigate the potential role of autophagy in ADSC apoptosis induced by high glucose.MethodsHuman ADSCs were cultured in normal or high-glucose medium for 6 h, 12 h, or 24 h. The effects of high glucose on ADSC autophagy, reactive oxygen species (ROS) production, and apoptosis were evaluated. The impact of autophagy on ROS production and apoptosis was explored by treatment with rapamycin or 3-methyladenine (3-MA). The c-jun kinase (JNK) signaling pathway was investigated by pharmacological disruption of SP600125.ResultsADSCs subjected to high glucose stress showed an obvious induction of autophagy and apoptosis and a significant increase in intracellular ROS levels. The JNK signaling pathway was confirmed to be involved in high glucose-induced autophagy. Pre-treatment with SP600125 or N-acetylcysteine reversed the effects of high glucose on the JNK signaling pathway and autophagy-related proteins. Pretreatment of ADSCs with 3-MA under high glucose stress induced a further increase in ROS levels compared to those of high glucose-treated cells. Furthermore, ADSCs pretreated with 3-MA under high glucose stress showed a marked increase in apoptosis compared with that of the cells treated with high glucose. Conversely, pre-treatment with rapamycin inhibited the apoptosis of ADSCs.ConclusionsTaken together, our data suggest that autophagy may play a protective role in high glucose-induced apoptosis in ADSCs. ROS/JNK signaling is essential in upregulating high glucose-induced autophagy. This study provides new insights into the molecular mechanism of autophagy involved in high glucose-induced apoptosis in ADSCs.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-1029-4) contains supplementary material, which is available to authorized users.

Background: Cell-assisted lipotransfer (CAL) promotes the survival of fat grafts with high vascular density and improves skin quality by increasing collagen content. However, no study has quantified the changes on the skin surface, and rigorous methodological evaluations are still lacking. Design: Fifty patients were recruited and randomly divided into two groups: an experimental group (n = 25) that underwent a stromal vascular fraction (SVF)-assisted fat graft and a control group (n = 25) that underwent fat graft only. Methods: The SVF cells were counted, tested in terms of viability, and characterized. The volumes of whole faces were determined by using a 3D scanner and Geomagic software preoperation, immediately after surgery, and 6 months postoperation. Facial skin qualities, including spots, wrinkles, texture, pores, UV spots, brown spots, red areas, and porphyrins, were detected by a VISIA skin detector preoperation and 6 months postoperation. A visual analog scale was used for clinical evaluation. Results: The cell pellet contained 1-3 × 10 7 /mL of fresh SVF cells. The cell viability exceeded 98%. The immunophenotyping characteristics and stemness were consistent with the features of adipose-derived stem cells (ADSCs). The survival rate of SVF-enriched fat grafts was significantly higher than that of control grafts: 77.6% ±11.6% versus 56.2% ±9.5% (p < 0.001). The VISIA values of wrinkles (19.3 ± 6.6 versus 10.9 ± 5.5, p < 0.001) and texture (15.8 ± 7.0 versus 10.3 ± 5.0, p < 0.01) were significantly higher in SVF-enriched group than in control group at 6 months postoperation. During long-term follow-up, the majority of patients in both groups were satisfied with the final facial esthetic results.

Advanced glycation end products/advanced glycation end products receptor (AGEs/AGER) interaction triggers reactive oxygen species (ROS) generation and activates downstream signal pathways and induces apoptosis in endothelial progenitor cells. A number of studies have revealed the involvement of microRNAs (miRNAs) in regulating intracellular ROS production and apoptosis. However, few studies explore the role of miRNAs in regulating the effect of adipose tissue-derived stem cells (ADSCs) in repairing diabetic wound and the associated cellular mechanisms remain unclear. In this study, ADSCs were exposed to AGEs, then siRNA for AGER was transfected into ADSCs. We found that AGEs/AGER axis induced ROS generation and apoptosis in ADSCs. AGEs treatment downregulated miR-5591-5p in ADSCs, which directly targeted AGER. miR-5591-5p suppressed AGEs/AGER axis-mediated ROS generation and apoptosis in ADSCs in vitro. In addition, miR-5591-5p promoted cell survival and enhanced the ability of ADSCs for repairing cutaneous wound in vivo. Furthermore, we confirmed that c-jun kinase (JNK) signal was involved in the inhibitory effect of miR-5591-5p on AGEs/AGER axis-induced ROS generation and apoptosis in ADSCs. Thus, these results indicated that miR-5591-5p targeting AGEs/AGER/JNK signaling axis possibly regulates the effect of ADSCs in repairing diabetic wound.

AURKA regulates apoptosis and autophagy in a diverse range of diseases and exhibits promising clinical efficacy; however, the role of AURKA in regulating adipose-derived stem cells (ADSCs) and repairing diabetic wound remains unclear. Here, we showed that ADSCs subjected to high glucose stress displayed an obvious induction of AURKA and FOXO3a, and a significant increase in autophagy and apoptosis. AURKA was confirmed to regulate autophagy through FOXO3a. AURKA-mediated autophagy inhibited high-glucosee induced apoptosis of ADSCs. Furthermore, co-immunoprecipitation and chromatin immunoprecipitation assays were employed to investigate the interaction of AURKA and FOXO3a. FOXO3a bound to its own promoter and transactivated its own expression. AURKA was found to interact with FOXO3a to regulate FOXO3a activity. In diabetic mice, ADSCs overexpressing AURKA led to a decrease of apoptosis of ADSCs and promoted wound healing in the skin. Taken together, our data suggest that transcriptional regulation of FOXO3a by highglucoseemediated AURKA is necessary for ADSCs autophagy. Our data reveal a potential therapeutic strategy for targeting AURKA involved in high-glucoseeinduced anti-apoptotic autophagy in ADSCs.

Background Nowadays, the use of cryopreserved fat tissue for soft tissue augmentation is common, except for its unpredictable fat graft absorption, and the toxicity of the cryoprotective agent remains a limitation. In this study, the effects of freezing stored fat tissue without a cryoprotector, and the addition of the stromal vascular fraction (SVF) on the survival of cryopreserved transplants was studied. Methods Lipoaspirates from six donors were processed and cryopreserved at − 20 °C, − 80 °C and − 196 °C, respectively. The authors evaluated the lipoaspirates in vitro, on the basis of fat tissue and SVF viability after cryopreservation. In vivo fat grafting was performed in nude mice. Six trenches were injected on the backs of mice. Cryopreserved tissues (− 20 °C, − 80 °C and − 196 °C) were injected on the right side, and the other side received the SVF combination. At 4 and 8 weeks after transplantation, the authors examined the weight, volume and morphology of the tissue and analyzed histochemical staining and immunohistochemistry (i.e., DIL, CD31 and VWF) to evaluate the survival of the fat grafts. Results After cryopreservation without the cryoprotective agent, adipose tissue maintained its morphology better in − 80 °C than − 20 °C and − 196 °C. SVF cells can retain their adhesive and proliferative properties after cryopreservation. Although cryopreservation caused damage to fat tissue, all explants showed intact adipocytes and vascular ingrowth. Most of all, the − 80 °C group had less graft resorption and fibrosis than the other temperature groups. There was increased survival of fat grafts in the SVF group compared with the control group. Conclusion In this study, the authors demonstrated that the storage temperature of − 80 °C was promising for 3 months of adipose tissue cryopreservation without a cryoprotective agent, and SVF could increase the survival rate of cryopreserved fat tissue. No Level Assigned This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .