Objective: To investigate the possibility of adipose tissue mesenchymal stem cell-derived microvesicles (ADSC-MVs) to improve the retention volume of fat transplantation. Methods: Human adipose tissue was obtained from 5 healthy female patients aged from 20 to 30 years, who came to the hospital for abdominal liposuction. Adipose tissue mesenchymal stem cells (ADSCs) were acquired by collagenase enzymatic hydrolysis. ADSC-MVs were isolated from the supernatant of cultured ADSCs through ultra-centrifugation, and characterized by transmission electron microscope and PKH26 staining. Sixteen BALB/c-nu nude mice were randomly divided into 2 groups (n=8, mice/group) by random number table method. In EV group, the mice were subcutaneously injected 0.35 ml human fat, with 7 μg ADSC-EVs (final concentration is 20 μg/ml), while 0.35 ml human fat were in blank group. The mice were sacrificed and the grafts were harvested at 1 month and 3 months after transplantation. Weight and volume of transplanted fat were tested. Morphology of adipocytes, fibrosis and necrosis of fat tissue were confirmed by HE staining. Blood vessel density were accessed by CD31 staining.SPSS 13.0 was used for statistical analysis and Student-t test was applied to compare the data from two groups. Results: One month after fat transplantation, the volume of fat grafts in blank group was lower than that in MV group. Besides, lipoliquefaction can be observed in fat grafts of blank group. Fat grafts in MV group had a higher volume and littler necrosis and lipolique faction. Three months after grafting, the volume of fat grafts in blank group [(0.057±0.009) ml] was significantly lower than that in MV group [(0.103±0.015) ml], t=8.117, P<0.001. MV group had an increased number of vessels (29.6±4.0/field) compared with grafts from the Blank group (23.0±2.4/field), t=2.825, P=0.022. Histological analysis revealed that the fat grafts in MV group consisted less fat necrosis and fibrosis than control group. Conclusions ADSC-MVs can improve the retention volume of fat transplantation.

Depressive disorder ranks as a major bur-den of disease worldwide,yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects.The lateral septum(LS)is thought to control of depression,however,the cellular and circuit substrates are largely unknown.Here,we identified a subpopulation of LS GABAergic adenosine A2A receptors(A2AR)-positive neurons mediating depres-sive symptoms via direct projects to the lateral habenula(LHb)and the dorsomedial hypothalamus(DMH).Activa-tion of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipula-tion of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive pheno-types.Thus,the optogenetic modulation(stimulation or inhibition)of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH,phenocopied depressive behaviors.Moreover,A2AR are upregulated in the LS in two male mouse mod-els of repeated stress-induced depression.This identifica-tion that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant poten-tial of A2AR antagonists,prompting their clinical transla-tion.