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

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.

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

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmab018 ◽

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.

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Preenrichment with Adipose Tissue-Derived Stem Cells Improves Fat Graft Retention in Patients with Contour Deformities of the Face

Stem Cells International ◽

10.1155/2019/5146594 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Muhammad M. Bashir ◽

Muhammad Sohail ◽

Fridoon J. Ahmad ◽

Mahmood S. Choudhery

Keyword(s):

Stem Cells ◽

Adipose Tissue ◽

Stem Cell ◽

Patient Satisfaction ◽

Fat Grafting ◽

Fat Graft ◽

Cell Group ◽

Patient Satisfaction Scores ◽

The Face ◽

Tissue Grafts

Quick absorption of adipose tissue grafts makes the outcomes less satisfactory for clinical applications. In the current study, adipose tissue grafts were mixed with adipose tissue-derived stem cells (ASCs) to improve retention of adipose tissue grafts and to make the clinical outcomes of fat grafting more reliable. Adipose tissue was either injected alone (conventional group) or mixed with ASCs (stem cell group) before injection. In both groups, adipose tissue was injected at the site of contour throughout layers of tissues till visual clinical symmetry with the opposite side was achieved. The volume of injected fat graft was measured after 72 hours and 6 months using a B-mode ultrasound device connected with a 12 MH frequency probe. The percentage reduction in the volume of injected fat, physician satisfaction scores (Ph-SCs), and patient satisfaction scores (P-SCs) were also recorded. After 6 months, there was significantly lower fat absorption in the stem cell group as compared to the conventional group. Mean physician and patient satisfaction scores were significantly improved in the stem cell group. No significant adverse effects were noted in any patient. Significantly lower absorption of graft due to the use of ASCs improves the clinical outcomes of conventional fat grafting for contour deformities of the face. The current preenrichment strategy is noninvasive, safe and can be applied to other diseases that require major tissue augmentation such as breast surgery. This trial is registered with NCT02494752.

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Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival: a randomised placebo-controlled trial

The Lancet ◽

10.1016/s0140-6736(13)61410-5 ◽

2013 ◽

Vol 382 (9898) ◽

pp. 1113-1120 ◽

Cited By ~ 305

Author(s):

Stig-Frederik Trojahn Kølle ◽

Anne Fischer-Nielsen ◽

Anders Bruun Mathiasen ◽

Jens Jørgen Elberg ◽

Roberto S Oliveri ◽

...

Keyword(s):

Stem Cells ◽

Adipose Tissue ◽

Graft Survival ◽

Ex Vivo ◽

Controlled Trial ◽

Autologous Fat ◽

Fat Grafts

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Supplementation with Extracellular Vesicles Derived from Adipose-Derived Stem Cells Increases Fat Graft Survival and Browning in Mice: A Cell-Free Approach to Construct Beige Fat from White Fat Grafting

Plastic & Reconstructive Surgery ◽

10.1097/prs.0000000000007819 ◽

2021 ◽

Vol 147 (5) ◽

pp. 882e-883e

Author(s):

Zhongyang Sun ◽

Hongyi Zhao

Keyword(s):

Stem Cells ◽

Graft Survival ◽

Extracellular Vesicles ◽

Fat Grafting ◽

Fat Graft ◽

Adipose Derived Stem Cells ◽

Beige Fat ◽

A Cell ◽

White Fat

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Characteristics and Potentiality of Human Adipose-Derived Stem Cells (hASCs) Obtained from Enzymatic Digestion of Fat Graft

Cells ◽

10.3390/cells8030282 ◽

2019 ◽

Vol 8 (3) ◽

pp. 282 ◽

Cited By ~ 28

Author(s):

Pietro Gentile ◽

Maria Piccinno ◽

Claudio Calabrese

Keyword(s):

Stem Cells ◽

Adipose Tissue ◽

Ex Vivo ◽

Stromal Vascular Fraction ◽

Enzymatic Digestion ◽

Histological Evaluation ◽

Fat Graft ◽

Adipose Derived Stem Cells ◽

Differentiation Potential ◽

New Therapeutic Approaches

Human adipose-derived stem cells localize in the stromal-vascular portion, and can be ex vivo isolated using a combination of washing steps and enzymatic digestion. For this study, we undertook a histological evaluation of traditional fat graft compared with fat graft enriched with stromal vascular fraction cells isolated by the Celution™ system to assess the interactions between cells and adipose tissue before the breast injection. In addition, we reported on histological analyses of biopsies derived from fat grafted (traditional or enriched with SVFs) in the breast in order to assess the quality of the adipose tissue, fibrosis and vessels. The hASCs derived from enzymatic digestion were systematically characterized for growth features, phenotype and multi-potent differentiation potential. They fulfill the definition of mesenchymal stem cells, albeit with a higher neural phenotype profile. These cells also express genes that constitute the core circuitry of self-renewal such as OCT4, SOX2, NANOG and neurogenic lineage genes such as NEUROD1, PAX6 and SOX3. Such findings support the hypothesis that hASCs may have a potential usefulness in neurodegenerative conditions. These data can be helpful for the development of new therapeutic approaches in personalized medicine to assess safety and efficacy of the breast reconstruction.

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Histone Deacetylase Inhibitor (Trapoxin A) Enhances Stemness Properties in Adipose Tissue Derived Mesenchymal Stem Cells

Drug Research ◽

10.1055/s-0044-102007 ◽

2018 ◽

Vol 68 (08) ◽

pp. 450-456 ◽

Cited By ~ 1

Author(s):

Leila Mousazadeh ◽

Effat Alizadeh ◽

Nosratollah Zarghami ◽

Shahryar Hashemzadeh ◽

Sedigheh Aval ◽

...

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Histone Deacetylase ◽

Histone Deacetylase Inhibitor ◽

Ex Vivo ◽

Osteogenic Potential ◽

Differentiation Potential ◽

Deacetylase Inhibitor

Abstract Back ground Adipose tissue derived mesenchymal stem cells (ASCs) have unique potential for regenerative cell therapies. However, during ex-vivo cultivation, they undergo considerable quality loss regarding their phenotypic properties, stemness genes expression and differentiation potential. Recent studies reported that the loss of stemness properties of MSCs is a result of chromatin histone deacetylations through in-vitro cultivation. The present work aimed to study the effect of Trapoxin A (TPX) as a histone deacetylase inhibitor (HDACi) on overall stemness properties of ASCs. Methods First, the effects of TPX treatments on ASCs viability and proliferation were evaluated using MTT assay. Second, the desired doses of TPX supporting ASCs proliferation were determined and the lack of their negative effects was confirmed by DAPI staining. In addition, the influence of TPX on cell cycle of ASCs and the mRNA levels of stemness genes were measured by flowcytometry and qPCR, respectively. Finally, the effect of TPX treatment on osteogenic potential of ASCs was studied. Results The results indicated that short time TPX treatment (nM concentrations) caused stimulation of proliferation and considerable percentage of ASCs entered to S-phase of cell cycle (p<0.05). Moreover, the findings demonstrated significant up-regulation of stemness markers genes (Oct-4, Sox-2, Nanog, TERT, Klf-4, Rex-1) (p<0.05) and enhanced osteogenic differentiation potential of ASC after TPX treatment. Conclusion The addition of low dose of TPX to the expansion medium could possibly enhance the stemness properties and prevent the quality decline of ex-vivo cultured ASCs.

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