Exosomes from adipose-derived mesenchymal stem cells promote survival of fat grafts by regulating macrophage polarization via let-7c

2021 ◽  
Vol 53 (4) ◽  
pp. 501-510
Author(s):  
Xiaoyan Hao ◽  
Yuan Guo ◽  
Rui Wang ◽  
Xueyuan Yu ◽  
Lin He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Graft Survival ◽  
Macrophage Polarization ◽  
Fat Grafting ◽  
Fat Graft ◽  
Fat Grafts ◽  
Enhancer Binding Protein ◽  
Key Factor ◽  
Anti Inflammatory

Abstract The rate of fat graft survival is a critical aspect of successful surgery and has been a matter of concern for over 20 years. Owing to their anti-inflammatory effects and regenerative property, adipose-derived mesenchymal stem cells (AD-MSCs) have been adapted for clinical application in fat grafting, although the mechanism underlying their action remains unclear. Recently, exosomes derived from MSCs were suggested as a better alternative, and these exosomes have also been applied in diverse clinical therapies. Accumulating evidence suggests that MSCs modulate macrophage differentiation via exosome secretion, and the connection between macrophage regulation and the rate of fat graft survival has been established. Here, we identified that let-7c, the key factor in the regulatory process, is shuttled by AD-MSC-derived exosomes to downregulate the transcription factor CCAAT/enhancer-binding protein (C/EBP)-δ. The downregulation of C/EBP-δ resulted in the attenuation of pro-inflammatory M1 macrophages and elevation of anti-inflammatory M2 macrophages. These results suggest that AD-MSC-derived exosomes promote the survival of fat grafts by regulating macrophage polarization via let-7c. This is the first study to elucidate the mechanism underlying the promotion of the fat graft survival rate by AD-MSCs and to evaluate the immunotherapeutic potential of AD-MSC-derived exosomes in fat grafting.

scholarly journals The angiogenic potential of CD271+ human adipose tissue-derived mesenchymal stem cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Richard J. P. Smith ◽  
Alessandro Faroni ◽  
James R. Barrow ◽  
Jamie Soul ◽  
Adam J. Reid
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Graft Survival ◽  
Ex Vivo ◽  
Fat Grafting ◽  
Surface Marker ◽  
Fat Graft ◽  
Angiogenic Potential ◽  
Gene And Protein Expression

Abstract Background Autologous fat grafting is often a crucial aspect of reconstructive and aesthetic surgeries, yet poor graft retention is a major issue with this technique. Enriching fat grafts with adipose tissue-derived mesenchymal stem cells (AD-MSCs) improves graft survival—however, AD-MSCs represent a heterogeneous population. Selection of subpopulations of AD-MSCs would allow the targeting of specific AD-MSCs that may benefit fat graft survival more than the general AD-MSC population. Methods Human AD-MSCs were selected for the surface marker CD271 using magnetic-activated cell sorting and compared to the CD271 negative phenotype.  These subpopulations were analysed for gene expression using Real-Time qPCR and RNA sequencing; surface marker characteristics using immunostaining; ability to form tubules when cultured with endothelial cells; and gene and protein expression of key angiogenic mediators when cultured with ex-vivo adipose tissue. Results Human AD-MSCs with the surface marker CD271 express angiogenic genes at higher levels, and inflammatory genes at lower levels, than the CD271− AD-MSC population. A greater proportion of CD271+ AD-MSCs also possess the typical complement of stem cell surface markers and are more likely to promote effective neoangiogenesis, compared to CD271− AD-MSCs. Conclusion Enriching grafts with the CD271+ AD-MSC subpopulation holds potential for the improvement of reconstructive and aesthetic surgeries involving adipose tissue.

scholarly journals CXCL16/CXCR6 Axis in Adipocytes Differentiated from Human Adipose Derived Mesenchymal Stem Cells Regulates Macrophage Polarization

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3410
Author(s):  
Seung-Cheol Lee ◽  
Yoo-Jung Lee ◽  
Inho Choi ◽  
Min Kim ◽  
Jung-Suk Sung
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Macrophage Polarization ◽  
Inflammatory Factors ◽  
M2 Macrophage ◽  
M2 Polarization ◽  
Chemokine Ligand ◽  
Anti Inflammatory ◽  
Underlying Mechanisms

Adipocytes interact with adipose tissue macrophages (ATMs) that exist as a form of M2 macrophage in healthy adipose tissue and are polarized into M1 macrophages upon cellular stress. ATMs regulate adipose tissue inflammation by secreting cytokines, adipokines, and chemokines. CXC-motif receptor 6 (CXCR6) is the chemokine receptor and interactions with its specific ligand CXC-motif chemokine ligand 16 (CXCL16) modulate the migratory capacities of human adipose-derived mesenchymal stem cells (hADMSCs). CXCR6 is highly expressed on differentiated adipocytes that are non-migratory cells. To evaluate the underlying mechanisms of CXCR6 in adipocytes, THP-1 human monocytes that can be polarized into M1 or M2 macrophages were co-cultured with adipocytes. As results, expression levels of the M1 polarization-inducing factor were decreased, while those of the M2 polarization-inducing factor were significantly increased in differentiated adipocytes in a co-cultured environment with additional CXCL16 treatment. After CXCL16 treatment, the anti-inflammatory factors, including p38 MAPK ad ERK1/2, were upregulated, while the pro-inflammatory pathway mediated by Akt and NF-κB was downregulated in adipocytes in a co-cultured environment. These results revealed that the CXCL16/CXCR6 axis in adipocytes regulates M1 or M2 polarization and displays an immunosuppressive effect by modulating pro-inflammatory or anti-inflammatory pathways. Our results may provide an insight into a potential target as a regulator of the immune response via the CXCL16/CXCR6 axis in adipocytes.

scholarly journals Salvianolic acid-B improves fat graft survival by promoting proliferation and adipogenesis

2021 ◽  
Author(s):  
Jia-Ming Sun ◽  
Chia-Kang Ho ◽  
Ya Gao ◽  
Chio-Hou Chong ◽  
Dan-Ning Zheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Graft Survival ◽  
Salvia Miltiorrhiza ◽  
Salvianolic Acid B ◽  
Fat Graft ◽  
Fat Transplantation ◽  
Salvianolic Acid ◽  
Fat Grafts

Abstract Background: Our previous study proved that Salvia miltiorrhiza could enhance fat graft survival by promoting adipogenesis. However, the effect of salvianolic acid B (Sal-B), the most abundant and bioactive water-soluble compound in Salvia miltiorrhiza, on fat graft survival has not yet been investigated.Objective: This study aims to investigate whether salvianolic acid B could improve fat graft survival and promote preadipocyte differentiation. The underlying mechanism has also been studied.Methods: In vivo, 0.2 ml of Coleman fat was transplanted into nude mice with salvianolic acid B. The grafts were evaluated by HE and IF at 2 and 4 weeks posttransplantation and by micro-CT at 4 weeks posttransplantation. In vitro, the adipogenesis and proliferative activities of salvianolic acid B were analyzed in cultured human adipose-derived stem cells (h-ADSCs) and 3T3-L1 cells to detect the mechanism by which salvianolic acid B affects graft survival.Results: In vivo, the weights and volumes of the fat grafts in the Sal-B-treated groups were significantly higher than those of the fat grafts in the control group. In addition, higher fat integrity and more viable adipocytes were observed in the Sal-B-treated groups. In vitro, salvianolic acid B showed the ability to promote 3T3-L1 and h-ADSC proliferation and adipogenesis.Conclusions: Our in vitro experiments demonstrated that salvianolic acid B can promote the proliferation of adipose stem cells and enhance the differentiation of adipose stem cells. Simultaneously, in vivo experiments showed that salvianolic acid B can improve the survival rate of fat transplantation. Therefore, our research shed light on the potential therapeutic usage of salvianolic acid B in improving the survival rate of fat transplantation.

The Effect of Minocycline on Fat Graft Survival and Apoptotic Pathway

2019 ◽  
Vol 35 (01) ◽  
pp. 096-102 ◽  
Author(s):  
Kırdar Güney ◽  
Bora Özel ◽  
Cemile Seymen ◽  
Çiğdem Elmas ◽  
Serhan Tuncer ◽  
...  
Keyword(s):  
Graft Survival ◽  
Study Groups ◽  
Fat Grafting ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Fat Graft ◽  
Albino Rats ◽  
Apoptotic Pathway ◽  
Fat Grafts ◽  
Dorsal Area ◽  
Wistar Albino Rats

AbstractVariable absorption rate is one of the biggest problems of fat grafting and one of the most important causes of fat graft volume loss is apoptosis. Minocycline is a tetracycline derivative and besides its antibacterial capacity, it has been widely using for anti-apoptotic effects. This study was designed to investigate the effect of minocycline on fat graft survival and adipocyte apoptosis. A total of two main and eight subgroups were designed and a total of 48 experimental animals, 6 in each group, were used. Fat grafts are obtained from Wistar albino rats and implanted to dorsal area of rats. Local and systemic minocycline was applied in the study groups. On the 9th day, apoptotic cells were detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling method and on the 90th day morphologic characteristics and viability of adipocytes were evaluated using histologic and immunohistochemical methods and statistically compared. This study revealed that the fat grafts were bigger, and they kept their structures better and they were more vascular in the minocycline groups and apoptosis was significantly lower in the minocycline groups. The authors demonstrated that minocycline increases fat graft survival and statistical improvement in apoptosis inhibition via using minocycline therapy has been shown.

scholarly journals Nanofat 2.0: Experimental Evidence for a Fat Grafting Rich in Mesenchymal Stem Cells

2017 ◽  
pp. 663-671 ◽  
Author(s):  
D. LO FURNO ◽  
S. TAMBURINO ◽  
G. MANNINO ◽  
E. GILIA ◽  
G. LOMBARDO ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Experimental Evidence ◽  
Tissue Repair ◽  
Fat Grafting ◽  
Proliferation Rate ◽  
Fat Grafts ◽  
Liquid Suspension ◽  
Adipose Mesenchymal Stem Cells ◽  
Marked Proliferation

Different strategies have been developed in the last decade to obtain fat grafts as rich as possible of mesenchymal stem cells, so exploiting their regenerative potential. Recently, a new kind of fat grafting, called “nanofat”, has been obtained after several steps of fat emulsification and filtration. The final liquid suspension, virtually devoid of mature adipocytes, would improve tissue repair because of the presence of adipose mesenchymal stem cells (ASCs). However, since it is probable that many ASCs may be lost in the numerous phases of this procedure, we describe here a novel version of fat grafting, which we call “nanofat 2.0”, likely richer in ASCs, obtained avoiding the final phases of the nanofat protocol. The viability, the density and proliferation rate of ASCs in nanofat 2.0 sample were compared with samples of nanofat and simple lipoaspirate. Although the density of ASCs was initially higher in lipoaspirate sample, the higher proliferation rate of cells in nanofat 2.0 virtually filled the gap within 8 days. By contrast, the density of ASCs in nanofat sample was the poorest at any time. Results show that nanofat 2.0 emulsion is considerably rich in stem cells, featuring a marked proliferation capability.

scholarly journals Do mesenchymal stem cells play a role in vocal fold fat graft survival?

2008 ◽  
Vol 41 (3) ◽  
pp. 460-473 ◽  
Author(s):  
V. Lo Cicero ◽  
E. Montelatici ◽  
G. Cantarella ◽  
R. Mazzola ◽  
G. Sambataro ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Graft Survival ◽  
Vocal Fold ◽  
Fat Graft
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