DOSE-DEPENDENT EFFECTS OF ADIPOSE TISSUE-DERIVED STROMAL VASCULAR FRACTION CELLS ON ANGIOGENESIS AND FIBROSIS IN HUMAN FAT GRAFTS

2014 ◽  
Vol 26 (03) ◽  
pp. 1450045
Author(s):  
Shou-Cheng Teng ◽  
Li-Ting Li ◽  
Shyi-Gen Chen ◽  
Tien-Mu Chen ◽  
Cheng-Hao Liao ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Stromal Vascular Fraction ◽  
Cyst Formation ◽  
Fat Graft ◽  
Fat Tissue ◽  
Fat Grafts ◽  
Regenerative Cells ◽  
Liposuction Surgery ◽  
Dose Dependent ◽  
Anti Inflammation

Adipose tissue is not only an ideal material for soft tissue filling and augmentation, but also a plentiful source of regenerative cells in adipose-derived stromal vascular fraction. Enriched fat tissue with adipose-derived stromal vascular fraction cells (ADSVFCs) can improve the fat graft survival, as shown in previous studies. The objective of this study is to estimate the effects of various dosages of ADSVFCs on fat grafts. We hypothesized that the improvement of ADSVFCs on fat transplantation quality would be dose dependent. Fat tissues were obtained by liposuction surgery. ADSVFCs were mixed into fat tissue, and the ADSVFC-enriched fat tissues were implanted subcutaneously into nude mice. The histological findings showed that the neoangiogenesis and integrity of grafted fat cells significantly increased with increasing dosages of ADSVFCs. Higher dosages of ADSVFCs also significantly reduced the side effects of the fat grafts, including reducing inflammation, cell infiltration, fibrosis and cyst formation. In conclusion, ADSVFC supplemented fat implants can improve angiogenesis and anti-inflammation. However, these effects of ADSVFCs on fat graft quality are dose dependent.

scholarly journals Effects of increased proliferation of human adipose tissue-derived mesenchymal stem cells by sphingosylphosphorylcholine on the survival of cryopreserved fat grafts

2018 ◽  
Vol 70 (3) ◽  
pp. 543-549
Author(s):  
Yong Bae ◽  
Ji Song ◽  
Kyeong Nam ◽  
Joo Kim ◽  
Su Nam
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Nude Mice ◽  
Soft Tissue Augmentation ◽  
Fat Graft ◽  
Saline Control ◽  
Control Group ◽  
Fat Tissue ◽  
Lipid Molecule ◽  
Fat Grafts

The use of cryopreserved adipose tissue for soft-tissue augmentation is common, but the unpredictability of fat graft viability remains a limitation. Human adipose-derived stem cells (hADSC) have been introduced to enhance viability and improve the survival of transplanted fat tissue. Sphingosylphosphorylcholine (SPC) is a bioactive lipid molecule involved in various cellular responses. SPC stimulates the proliferation of various cell types such as hADSC. We demonstrated the effects of hADSC and SPC on the survival of cryopreserved fat grafts in nude mice. The cryopreserved fat grafts were treated with hADSC or hADSC+SPC, and a normal saline (control) mixture in BALB/c male nude mice. We examined the weight and volume of the mice in each group (n=11) at 8 weeks after transplantation to evaluate the survival of the fat tissue. The hADSC group showed increased weight and volume compared with the control group. The hADSC+SPC group showed a higher survival rate in terms of weight and volume than the control or hADSC group. In addition, the hADSC+SPC treatment significantly increased the expression of angiogenic factors. These results suggest the potential clinical utility of hADSC+SPC.

scholarly journals Engineered Fat Graft Enhanced with Adipose-Derived Stromal Vascular Fraction Cells for Regenerative Medicine: Clinical, Histological and Instrumental Evaluation in Breast Reconstruction

2019 ◽  
Vol 8 (4) ◽  
pp. 504 ◽  
Author(s):  
Pietro Gentile ◽  
Donato Casella ◽  
Enza Palma ◽  
Claudio Calabrese
Keyword(s):  
Breast Reconstruction ◽  
Preoperative Evaluation ◽  
Three Dimensional ◽  
Stromal Vascular Fraction ◽  
Fat Graft ◽  
Control Group ◽  
Study Group ◽  
Fat Tissue ◽  
Calvarial Defects

The areas in which Stromal Vascular Fraction cells (SVFs) have been used include radiotherapy based tissue damage after mastectomy, breast augmentation, calvarial defects, Crohn’s fistulas, and damaged skeletal muscle. Currently, the authors present their experience using regenerative cell therapy in breast reconstruction. The goal of this study was to evaluate the safety and efficacy of the use of Engineered Fat Graft Enhanced with Adipose-derived Stromal Vascular Fraction cells (EF-e-A) in breast reconstruction. 121 patients that were affected by the outcomes of breast oncoplastic surgery were treated with EF-e-A, comparing the results with the control group (n = 50) treated with not enhanced fat graft (EF-ne-A). The preoperative evaluation included a complete clinical examination, a photographic assessment, biopsy, magnetic resonance (MRI) of the soft tissue, and ultrasound (US). Postoperative follow-up took place at two, seven, 15, 21, 36 weeks, and then annually. In 72.8% (n = 88) of breast reconstruction treated with EF-e-A, we observed a restoration of the breast contour and an increase of 12.8 mm in the three-dimensional volume after 12 weeks, which was only observed in 27.3% (n = 33) of patients in the control group that was treated with EF-ne-A. Transplanted fat tissue reabsorption was analyzed with instrumental MRI and US. Volumetric persistence in the study group was higher (70.8%) than that in the control group (41.4%) (p < 0.0001 vs. control group). The use of EF-e-A was safe and effective in this series of treated cases.

scholarly journals New Mechanical Fat Separation Technique: Adjustable Regenerative Adipose-tissue Transfer (ARAT) and Mechanical Stromal Cell Transfer (MEST)

2020 ◽  
Vol 2 (4) ◽  
Author(s):  
H Eray Copcu ◽  
Sule Oztan
Keyword(s):  
Adipose Tissue ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Retention Rate ◽  
High Rate ◽  
Cell Transfer ◽  
Fat Tissue ◽  
Cell Counts ◽  
Tissue Transfer ◽  
Regenerative Cells

Abstract Background Adipose tissue is not only a very important source of filler but also the body’s greatest source of regenerative cells. Objectives In this study, adipose tissue was cut to the desired dimensions using ultra-sharp blade systems to avoid excessive blunt pressure and applied to various anatomical areas—a procedure known as adjustable regenerative adipose-tissue transfer (ARAT). Mechanical stromal cell transfer (MEST) of regenerative cells from fat tissue was also examined. Methods ARAT, MEST, or a combination of these was applied in the facial area of a total of 24 patients who were followed for at least 24 months. The integrity of the fat tissue cut with different diameter blades is shown histopathologically. The number and viability of the stromal cells obtained were evaluated and secretome analyses were performed. Patient and surgeon satisfaction were assessed with a visual analog scale. Results With the ARAT technique, the desired size fat grafts were obtained between 4000- and 200-micron diameters and applied at varying depths to different aesthetic units of the face, and a guide was developed. In MEST, stromal cells were obtained from 100 mL of condensed fat using different indication-based protocols with 93% mean viability and cell counts of 28.66 to 88.88 × 106. Conclusions There are 2 main complications in fat grafting: visibility in thin skin and a low retention rate. The ARAT technique can be used to prevent these 2 complications. MEST, on the other hand, obtains a high rate of fat and viable stromal cells without applying excessive blunt pressure. Level of Evidence: 4

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

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 282 ◽  
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.

Abstract WP147: Cell-Free Fat Extract Promotes Angiogenesis in a Mouse Model of Cerebral Ischemia

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Hui Shen ◽  
Guo-Yuan Yang ◽  
Yaohui Tang ◽  
Zhijun Zhang ◽  
Ziyou Yu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Ischemic Stroke ◽  
Growth Factors ◽  
Brain Atrophy ◽  
Therapeutic Agent ◽  
Stromal Vascular Fraction ◽  
Focal Ischemia ◽  
Fat Tissue ◽  
Cell Based Therapy ◽  
Neurobehavioral Outcomes

Background: Adipose tissue and its derivatives including adipose-derived stem cells and stromal vascular fraction (SVF) showed effective in the treatment of ischemic stroke. However, cell-based therapy for clinical application has been hindered by limitations such as safety, immunogenicity issues, and difficulties in cell preservation, transportation, and phenotype control. Here, we aimed to produce a cell-free extract directly from human fat tissue and evaluate its potential therapeutic efficacy for treating ischemic stroke. Methods: Cell-free aqueous extract from human fat tissue was obtained using mechanical emulsification method. Twenty adult CD-1 mice were subjected to 60-minute middle cerebral artery occlusion. Immediately after ischemia, 0.1 ml fat extract was intravenously injected into ischemic mice through tail vein every other day for 14 days. Brain atrophy volume and neurobehavioral outcomes were examined at 14 days after focal ischemia. The occurrence of angiogenesis was evaluated by immunostaining and ELISA, and growth factors contained in the fat extract was analyzed to explore the molecular mechanism of fat extract treatment. Results: Our results showed that brain atrophy volume reduced and neurobehavioral outcomes improved at 3 ,7 and 14 days of focal ischemia in the fat extract treated mice compared to the controls ( p <0.05). Furthermore, fat extract treatment increased microvessel density at 14 days after focal ischemia (p<0.05). ELISA showed that fat extract contained high levels of several growth factors such as HGF, VEGF, bFGF, BDNF, and GDNF. Conclusions: We developed a novel cell-free therapeutic agent, fat extract, produced from human adipose tissue. The fat extract contained high level of growth factors such as HGF, VEGF, bFGF, BDNF, and GDNF, which plays important role of promoting angiogenesis and reduced ischemic brain injury in the mouse brain, suggesting that the fat extract is a novel cell-free therapeutic agent in the treatment of ischemic stroke.

scholarly journals Improvement of the Survival of Human Autologous Fat Transplantation by Adipose-Derived Stem-Cells-Assisted Lipotransfer Combined with bFGF

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Aimei Jiang ◽  
Ming Li ◽  
Wenjing Duan ◽  
Yilong Dong ◽  
Yanmei Wang
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Histological Analysis ◽  
Angiogenic Factors ◽  
Fat Graft ◽  
Adipose Derived Stem Cells ◽  
Fat Transplantation ◽  
Autologous Fat ◽  
Fat Grafts ◽  
Autologous Fat Transplantation

Adipose-derived stem cells (ASCs) transplanted along with autologous adipose tissue may improve fat graft survival; however, the efficacy of ASCs has been diluted by low vascularization. This study was designed to test the hypothesis that basic fibroblast growth factor (bFGF) may improve the effects of ASCs because it owns the property to boost angiogenesis. In the present study, human fat tissues were mixed with ASCs, ASCs plus 100 U bFGF, or medium as the control and then injected subcutaneously into immunologically compromised nude mice for 12 weeks. Our findings demonstrated that mixture with the ASCs significantly increased the weight and volume of the fat grafts compared to control grafts, and histological analysis revealed that both ASCs and ASCs plus bFGF grafts consisted predominantly of adipose tissue and had significantly less fibrosis but greater microvascular density compared with control and also grafts mixed with ASCs had a high expression of angiogenic factors. More importantly, the bFGF treated fat grafts shown elevate in survival, vascularization, and angiogenic factors expression when compared with the grafts that received ASCs alone. These results indicated that bFGF together with ASCs can enhance the efficacy of autologous fat transplantation and increase blood vessel generation involved in the benefits from bFGF.

scholarly journals A Prospective and Controlled Clinical Trial on Stromal Vascular Fraction Enriched Fat Grafts in Secondary Breast Reconstruction

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
L. A. L. Tissiani ◽  
N. Alonso
Keyword(s):  
Breast Reconstruction ◽  
Controlled Trial ◽  
Statistical Significance ◽  
Stromal Vascular Fraction ◽  
Cell Counting ◽  
Fat Graft ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Fat Grafts ◽  
Significant Difference

Background.Fat grafting is a tremendous tool in secondary breast reconstruction. Stromal vascular fraction (SVF) enriched fat grafts have been presenting promising results regarding volume maintenance.Methods.We developed a method that produces a superior SVF enrichment rate (2 : 1) in the operating theatre. This prospective and controlled trial analyzed quantitatively and qualitatively fat grafts with (stem cells group, SG) and without (control group, CG) SVF enrichment in secondary breast reconstruction, through MRI-based volumetry, immunophenotyping, and cell counting. Also, patient satisfaction, aesthetic outcomes, and complications were analyzed.Results.Volumetric persistence in the SG was 78,9% and 51,4% in the CG; however it did not reach statistical significant difference. CD90 was the only marker highly expressed in the SG and showed a positive correlation with volumetric persistence (r=0.651,p=0.03). Fat necrosis occurred in 4 patients in the SG and in none in the CG. Patients in the CG showed a trend to be more satisfied. Considering aesthetics, both groups presented improvements. No locoregional recurrences were observed.Conclusions.Results are encouraging despite the fact that SVF enrichment in a higher supplementation rate did not improve, with statistical significance, fat graft volumetric persistence. Enriched fat grafts have proven to be safe in a 3-year follow-up.

scholarly journals Necroptosis in Macrophage Foam Cells Promotes Fat Graft Fibrosis in Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Xihang Chen ◽  
Zilong Deng ◽  
Jingwei Feng ◽  
Qiang Chang ◽  
Feng Lu ◽  
...  
Keyword(s):  
Collagen Synthesis ◽  
Foam Cells ◽  
Fat Graft ◽  
Raw 264.7 ◽  
Fat Tissue ◽  
Raw 264.7 Macrophages ◽  
Tissue Fibrosis ◽  
Fat Grafts ◽  
Macrophage Foam Cells

Background: Fibrosis is a major grafting-related complication that leads to fat tissue dysfunction. Macrophage-induced inflammation is related to the development of fat tissue fibrosis. Necroptosis is a recently discovered pathway of programmed cell necrosis that results in severe inflammation and subsequent tissue fibrosis. Thus, in this study, we investigated the role of macrophage necroptosis in fat graft fibrosis and the underlying mechanisms.Methods: Fibrosis and necroptosis were investigated in mouse fat tissue before and after grafting. An in vitro “crown-like” structure (CLS) cell culture model was developed by co-culturing RAW 264.7 macrophages with apoptotic adipocytes to reproduce in vivo CLS macrophage-adipocyte interactions. Lipid uptake and necroptosis in CLS macrophages were analyzed using Oil-Red-O staining, western blotting, and immunofluorescence. RAW264.7 macrophages were cultured alone or with apoptotic adipocytes and treated with a necroptosis inhibitor (Nec-1 or GSK872) to explore the paracrine effect of necroptotic CLS macrophages on collagen synthesis in fibroblasts in vitro. Mice were treated with Nec-1 to analyze the effect of blocking necroptosis on fat graft fibrosis.Results: Fibrosis was increased after grafting in fat grafts of mice. Macrophages clustered around apoptotic adipocytes or large oil droplets to form a typical CLS in fibrotic depots. This was accompanied by formation and necroptosis of macrophage foam cells (MFCs) in CLSs. RAW 264.7 macrophages co-cultured with apoptotic adipocytes induced CLS formation in vitro, and lipid accumulation in CLS macrophages resulted in the formation and necroptosis of MFCs. Necroptosis of MFCs altered the expression of collagen I and VI in fibroblasts via a paracrine mechanism involving inflammatory cytokines/chemokines, which was reversed by GSK872 or Nec-1 treatment. Furthermore, treatment with Nec-1 ameliorated fat graft fibrosis in mice.Conclusion: Apoptotic adipocytes induced necroptosis of MFCs, and necroptosis of these cells activated collagen synthesis in fibroblasts via a paracrine mechanism. Inhibition of necroptosis in macrophages is a potential approach to prevent fibrosis in fat grafts.

scholarly journals Sphenoid Sinus Fat Packing in Transsphenoidal Surgery: Long-Term Fate Assessment Using Magnetic Resonance Imaging

2020 ◽  
Vol 27 (1) ◽  
pp. 28-33
Author(s):  
Chi Sang Hwang ◽  
Kum Whang ◽  
Hee Sung Chae ◽  
Hyun Su Lee ◽  
Chung Seok Lee ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Sphenoid Sinus ◽  
Fat Graft ◽  
Cerebrospinal Fluid Leakage ◽  
Fat Tissue ◽  
Resonance Imaging ◽  
Fat Grafts ◽  
Mri Scans

Background and Objectives: Following the transsphenoidal approach (TSA), appropriate sphenoid sinus fat packing has been preferred to prevent postoperative cerebrospinal fluid leakage; however, studies on the behavior of fat tissue transplanted in the sphenoid sinus are lacking. This study aimed to determine the long-term fate of these fat grafts using magnetic resonance imaging (MRI).Subjects and Method: A total of 139 postoperative MRI scans of 41 patients who underwent sphenoid sinus fat packing using the standard TSA were evaluated. Additionally, MRI time series indicating the vital fat volumes were assessed postoperatively.Results: In 82.9% of cases, the fat volumes measured in the final MRI scans declined to <20% of the initial volumes; only 4.9% of cases exhibited declines to >60% of the initial volume. The fat tissue volume decreased significantly with time, with a median half-life of 18 months. Typically, the sphenoid sinus was eventually almost filled with air rather than transplanted fat. In the subgroup analysis, the fat clearance rate was significantly lower in patients with residual tumors than in those without such remnants (p=0.013).Conclusion: Long-term MRI surveillance of fat grafts in the sphenoid sinus revealed that the transplanted fat graft had degraded and was gradually eliminated.

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