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Enhancing High-Quality Fat Survival: A Novel Strategy Using Cell Free Fat Extract

ABSTRACT: High-quality fat (HQF) contains a higher proportion of stromal vascular fraction, adipose-derived stem cells, and extracellular matrix components, surpassing the effectiveness of the traditional Coleman fat grafting method and improving volumetric filling. However, this high-quality fat strategy inevitably leads to a significant amount of unused fat being wasted. CEFFE, a cell-free extract derived from autologous fat tissue, is enriched with bioactive molecules. In this study, we further process the remaining fat from preparing HQF into CEFFE to promote the survival of transplanted fat. Our study introduces CEFFE, from the remaining fat from preparing HQF, as a promising adjunct to HQF grafting, showcasing notable enhancements in graft survival, adipose tissue integrity, and angiogenesis. The observed positive effects on ADSCs, including augmented stemness and adipogenic differentiation potential, further contribute to the overall improvement in fat graft outcomes. While these findings present a novel strategy for addressing the limitations of traditional fat grafting, additional research and clinical studies are imperative to validate the long-term efficacy, safety, and broader applicability of CEFFE in enhancing fat graft survival and promoting tissue regeneration.

ORGANISM(S): Homo sapiens

PROVIDER: GSE253141 | GEO | 2024/01/16

REPOSITORIES: GEO

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Glutathione supplementation improves fat graft survival by inhibiting ferroptosis via the SLC7A11/GPX4 axis

Project description:Background: Autologous fat grafting is hampered by unpredictable graft survival, which is potentially regulated by ferroptosis. Glutathione (GSH), a powerful antioxidant used in tissue preservation, has ferroptosis-regulating activity; however, its effects on fat grafts are unclear. This study investigated the effects and mechanisms of GSH in fat graft survival. Methods: Human lipoaspirates were transplanted subcutaneously into the backs of normal saline-treated (control) or GSH-treated nude mice. Graft survival was evaluated by magnetic resonance imaging and histology. RNA sequencing was performed to identify differentially expressed genes and enriched pathways. GSH activity was evaluated in vitro using an oxygen and glucose deprivation (OGD) model of adipose-derived stem cells. Results: Compared with control group, GSH induced better outcomes, including superior graft retention, appearance, and histological structures. RNA sequencing suggested enhanced negative regulation of ferroptosis in the GSH-treated grafts, which showed reduced lipid peroxides, better mitochondrial ultrastructure, and SLC7A11/GPX4 axis activation. In vitro, OGD-induced ferroptosis was ameliorated by GSH, which restored cell proliferation, reduced oxidative stress, and upregulated ferroptosis defense factors. Conclusions: Our study confirms that ferroptosis participates in regulating fat graft survival and that GSH exerts a protective effect by inhibiting ferroptosis. GSH-assisted lipotransfer is a promising therapeutic strategy for future clinical application.

2023-05-08 | GSE231511 | GEO

Dll4 inhibition promotes angiogenesis and graft volume retention in cell-assisted lipotransfer

Project description:Purpose: Autologous fat grafting is one of the most effective and safest treatment for soft tissue restoration and augmentation, and many efforts has been done to improve its efficiency including adipose tissue derived stem cell (ASC) supplementation. Here, we evaluated the role of Notch ligand Delta-like ligand 4 (Dll4) in angiogenesis in grafted fat and the effect on graft survival using the murine fat graft model, and its impact on the ASC supplementation. Methods: We performed RNA-seq analysis of 3 mouse fat graft groups: 1) control fat grafts, 2) ASC added fat graft, and 3) ASC added fat graft with Dll4 inhibition. The fat grafts were harvested 8 weeks after grafting (n=4), and generated mRNA profiles by deep sequencing using Illumina NovaSeq 6000. Results: We found that when we treated Dll4 blocking antibody to inhibit Dll4, which was highly expressed in endothelial cells (ECs) of grafted fat, angiogenesis in the grafted fat was significantly induced, promoting fat graft retention. In addition, this effect was shown to synergistically improve the fat graft retention when ASCs were concomitantly supplemented. Transcriptome analysis further identified that the expression of the junctional proteins was increased in the ECs and inflammatory processes were downregulated in the grafted fat with ASC supplementation and Dll4 inhibition. Conclusions: This study serves as a basis for developing new potential therapeutic approaches to improve graft retention after cell-assisted transfer by Dll4 inhibition.

2023-12-05 | GSE190243 | GEO

RNA-seq Analysis of Fat Tissue Before and After Grafting in Mice

Project description:Purpose: To investigate the influence of grafting on adipose tissues, samples were collected from the inguinal fat tissues of mice before grafting and 1 week after grafting. Methods: The RNA-seq analysis was performed by Novogene (Beijing, China). Total RNA was drawn from the tissues with TRIzol reagent (Absin, Shanghai, China). Transcriptome sequencing were performed by using the Illumina HiSeq X Ten (Novogene Bioinformatics Technology Co., Ltd., Beijing, China). Mapping of 150-bp paired-end reads to the genes was undertaken. Result: In fat tissues one week after grafting, 28145 genes were detected. And 3271 genes were found to be upregulated, while 3745 genes were downregulated (padj < 0.05 and log2(FC) > 1), when compared with that in the natural fat tissues. Conclusions: Our study firstly reported the differentially expressed genes in adipose tissues after grafting, providind a valuable reference for fat grafting studies.

2022-02-25 | GSE197183 | GEO

RNA sequencing of RAW264.7 with or without Sal-B and LPS addition

Project description:Autologous fat grafting (AFG), although an appealing approach to repair soft tissue defects, has various complications. Excessive inflammation at the transplant site is one of the main reasons for the poor effect of fat transplantation and occurrence of complications. Our previous study proved that Salvia miltiorrhiza can enhance fat graft survival. Salvianolic acid B (Sal-B) is the most abundant and bioactive water-soluble compound in Salvia miltiorrhiza and has anti-inflammatory effects on other diseases. Therefore, we hypothesized that salvianolic acid B could improve the effect of fat grafts by inhibiting inflammation.

2023-09-14 | GSE186886 | GEO

Paracrine Signaling in Visceral Fat

Project description:Accumulation of visceral (VIS) as opposed to subcutaneous (SUB) fat is a predictor of metabolic disorders, insulin resistance, and cardiovascular disease. This is due in part to the limited capacity of VIS fat to buffer lipids allowing them to deposit in insulin-sensitive tissues, thus impairing insulin action. In addition, VIS adipose tissue is more prone to fibrosis and inflammation, which in turn contributes to the pathogenesis of metabolic disease. Mechanisms underlying selective hypertrophic growth and tissue remodeling properties of VIS fat are not well understood. We and others identified subsets of adipose progenitors (APs) unique to VIS fat with differential adipogenic capacity. We named these CD34+ APs VIS low and VIS high based on low or high CD34 expression respectively. Despite sharing the same developmental origin, VIS low APs are adipogenic whereas VIS high APs are not. Furthermore, VIS high APs inhibit adipogenic differentiation of SUB and VIS low APs in vitro through the secretion of soluble inhibitory factor(s) including insulin-like growth factor binding protein 2 (Igfbp2). The number of VIS high APs increased with VIS adipose tissue expansion and their abundance in vivo causes hypertrophic growth, fibrosis, inflammation and impaired glucose and insulin tolerance. This study unveil the presence of APs unique to VIS fat involved in the paracrine regulation of adipogenesis and tissue remodeling.

2024-05-21 | PXD014672 | Pride

Graft junction transcriptome between tomato and pepper over time

Project description:We report transcripts from tomato:tomato and pepper:pepper self-grafts, and tomato:pepper and pepper:tomato hetergrafts over 4 time points: 24 hours after grafting, 3 days after grafting, 5 day after grafting, and 2 weeks after grafting Examination of 4 graft combinations over 4 time points

2021-08-02 | GSE131700 | GEO

Effect of autologous fat grafting on Localized Scleroderma (morphea)

Project description:Localized scleroderma (LoS), or morphea, refers to a group of rare autoimmune connective tissue diseases. Autologous fat grafting was able to correct volume loss in patients with LoS to improve facial disfigurement.However, whether it could exert a positive effect on reversing skin sclerosis remains unclear.

2023-11-20 | GSE247804 | GEO

Transcriptional analysis for cell-cell communication during graft union development in Arabidopsis

Project description:Grafting is an ancient cloning method that has been used widely for thousands of years in agricultural practices. However, the molecular mechanisms for graft union development are still largely unknown. The developmental stage of graft union was characterized based on micrografting method. Microarray data revealed a signal exchange process between cells of scion and stock at 1dag, which reestablished the communication network in graft union. This process was concomitant with the cleaning of cell debris, and both of the processes were initiated by a wound-induced program. The results demonstrate the feasibility and potential power of investigating various plant developmental processes by this method and represent a primary and significant step in interpretation of the molecular mechanisms underlying graft union development. WT/WT seedling grafts of 22-26 hours after grafting were collected for microarray, intact WT seedlings and ungrafted scions and stocks were as control. All three types of sample, grafts (marked as A: whole graft), ungrafted scions and stocks (marked as B: mixture of ungrafted scions and stocks) and intact seedlings (marked as C: whole seedling), were collected at the same time of 22-26 hours after grafting. For sample B, scions and stocks were cut at the same time during grafting. For sample C, intact seedlings were also reserved during grafting. Data were firstly compared between sample A and C, differential expressed probe sets were than tested based on A and B to obtain graft-specific probes.

2012-05-02 | E-GEOD-36447 | biostudies-arrayexpress

Identification of Hipk2 as a central regulator of white fat development

Project description:Homeodomain interacting protein kinase 2 (Hipk2) has previously been implicated in control of several transcription factors involved in embryonic development, apoptosis, cell proliferation and tumour development1–3. Analysis of gene expression in tissues from genetically heterogeneous mouse or human populations can reveal motifs associated with the structural or functional components of the tissue, and may predict roles for genes of unknown function4,5. Here we have applied this network strategy to uncover a novel role for the Hipk2 gene in the transcriptional system controlling adipogenesis. Both in vitro and in vivo models were used to show that knockdown or loss of Hipk2 specifically inhibits white adipose cell differentiation and tissue development. In addition, loss of Hipk2 leads to induction of pockets of multilocular brown fat-like cells in remaining white adipose depots. These cells express markers of brown and beige fat such as uncoupling protein 1 (Ucp1) and transmembrane protein 26 (Tmem26), and thermogenic genes including PPAR-γ coactivator 1a (Ppargc1a), and cell death-inducing DFFA-like effector a (Cidea). These changes are accompanied by increased insulin sensitivity in Hipk2 knock-out mice and reduced high fat diet-induced weight gain, highlighting a potential role for this kinase in diseases such as diabetes and obesity. Our study underscores the versatility and power of a readily available tissue, such as skin, for network modelling of systemic transcriptional programs involved in multiple pathways, including lipid metabolism and adipogenesis. Mammary fat pads from 115 distinct untreated 8 week old [FVB/N x Spret/Ei] x FVB/N Backcross mice

2014-01-01 | E-GEOD-46077 | biostudies-arrayexpress

Proteomics analysis of insulin sensitive tissues in high fat diet fed mice

Project description:The popularity of high fat foods in modern society has been associated with epidemic of various metabolic diseases characterized by insulin resistance, the pathology of which involves complex interactions between multiple tissues such as liver, skeletal muscle and white adipose tissue (WAT). To uncover the mechanism by which excessive fat impairs insulin sensitivity, we conducted a multi- tissue study by using TMT-based quantitative proteomics. 3-week-old ICR mice were fed with high fat diet (HFD) for 19 weeks to induce insulin resistance. Liver, skeletal muscle and epididymal fat were collected for proteomics screening. Additionally, PRM was used for validating adipose differential proteins. By comparing tissue-specific protein profiles of HFD mice, multi-tissue regulation of glucose and lipid homeostasis and corresponding underlying mechanisms was systematically investigated and characterized. NC: normal birth weight + chow diet; NH: normal birth weight + high fat diet; LC: low birth weight + chow diet; LH: low birth weight + high fat diet.

2022-01-26 | PXD021046 | Pride

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