Autologous Fat Graft Survival Research Articles

Delivery of microRNA-423-5p by exosome from adipose-derived stem/stromal cells inhibits DVL3 to potentiate autologous fat graft survival through adipogenesis and inflammatory response.

Autologous fat grafting represents a reconstructive technique but is limited by unstable graft retention. Based on existing reports and bioinformatics prediction, we hypothesized that delivering exosomes from human adipose-derived stem/stromal cells (hADSC-Exo) would increase fat graft survival and further explore the mechanism. hADSC-Exo were extracted and identified. An autologous fat grafting model was established using donor and recipient mice, followed by hADSC-Exo treatment. hADSC-Exo promoted the retention of autologous fat grafts in mice, along with increased adipocyte activity, angiogenesis, and decreased inflammation in grafts. Moreover, hADSC-Exo potentiated the adipose differentiation of 3T3-L1 cells, enhanced the angiogenic and migratory capacity of human umbilical vein endothelial cells, and inhibited the inflammation and viability of RAW 264.7 cells. The therapeutic effect of hADSC-Exo on fat grafting was associated with the delivery of microRNA (miR)-423-5p. Deletion of miR-423-5p in Exo impaired the function of hADSC-Exo on fat retention. miR-423-5p bound to DVL3 to suppress DVL3 expression, and DVL3 deletion promoted adipose differentiation of 3T3-L1 cells. In conclusion, our findings further widen the theoretical basis of the clinical application of hADSC-Exo in autologous fat grafts.

Pluronic F-127 Hydrogel Loaded with Human Adipose-Derived Stem Cell-Derived Exosomes Improve Fat Graft Survival via HIF-1α-Mediated Enhancement of Angiogenesis.

Autologous fat grafting is playing an increasingly important role in plastic surgery. However, high absorption and low survival of autologous fat grafts limit their clinical application. This study aimed to investigate whether human adipose-derived stem cell-derived exosomes (hASC-Exos) encapsulated in a PF-127 hydrogel can improve the survival of autologous fat grafts and to elucidate the underlying mechanisms. Exosomes were isolated from hASCs and identified using transmission electron microscopy, nanoparticle tracking analysis and Western blotting. We performed functional assays in vitro to assess the effect of hASC-Exos on proliferation, migration, and tube formation as well as their regulatory role in the HIF-1α/VEGF signaling pathway. hASC-Exos encapsulated in the PF-127 hydrogel were used as an in vivo autologous fat graft model. The effects of the PF-127 hydrogel/hASC-Exos and the role of the HIF-1α/VEGF signaling pathway in promoting angiogenesis in an autologous fat grafting model were assessed. hASC-Exos were taken up by human umbilical vein endothelial cells and enhanced their proliferation, migration, and tubule formation in vitro. The effects of hASC-Exos on promoting angiogenesis were mediated by the HIF-1α/VEGF signaling pathway. Moreover, we fabricated a PF-127 hydrogel for the sustained release of hASC-Exos, and in vivo results showed that hASC-Exos encapsulated in PF-127 hydrogel improved the survival of autologous fat grafts. Our findings indicated that hASC-Exos encapsulated in PF-127 hydrogel serve as a key regulator of angiogenesis by activating the HIF-1α/VEGF signaling pathway and provide a promising strategy for autologous fat grafting treatment.

The Effect of Human Umbilical Cord-Derived Lyophilized Stem Cells on Fat Graft Viability: An Experimental Study.

The extended use of autologous adipose tissue has increased the importance of the viability of fat graft cells. This experimental animal study assesses the effects of lyophilized mesenchymal stem cells on the viability and survival of autologous fat grafts. For this prospective treatment control study, 27 male Wistar albino rats were divided into three groups, each containing nine animals. In Group 1 (control), an incision was made in the right inguinal region, and the skin was closed with 4/0 prolene sutures. In Groups 2 and 3, fat pads collected from the right groin of the rats were lipoaspirated and placed on the sternum as a subcutaneous fat graft. The skin was then closed with 4/0 prolene sutures. Saline was added to the fat grafts of the Group 2 (sham) rats, and placenta-derived mesenchymal stem cell lyophilizate (MSC-L) was administered to the fat graft in the Group 3 (treatment) rats. After three months of treatment, the adipose tissue harvested from Group 1 and the fat grafts taken from Groups 2 and 3 were assessed histopathologically, stereologically and biochemically. Adipose tissue volume was lower in Group 2 than in Groups 1 and 3, and the adipose tissue treated with MSC-L in Group 3 was better preserved than that in Group 1. Connective tissue and vascular volumes were greater in Group 3 than those in the other groups. The normal structures of adipocytes, fibrous tissues and vessels were better preserved in Group 3 than in Group 2, and a large number of new blood vessels were noted to have formed in Group 3. Damaged cystic cells, areas of calcification and degenerated adipocytes were noted in Group 2, while the G3PDH levels increased significantly more in Group 3 than in Group 2. It was shown that MSC-L treatment plays an active role in maintaining the volume and survival of fat grafts by promoting neovascularization in this animal experimental study. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Liquid Phase Concentrated Growth Factor Improves Autologous Fat Graft Survival In Vivo in Nude Mice.

The present study aimed to explore the efficacy and safety profile of liquid phase concentrated growth factor (LPCGF) in promoting autologous fat graft survival. LPCGF/PRP was mixed with human fat tissues at different proportions and transplanted into nude mice. Three months after transplantation, the implanted fat tissues were retrieved for analysis. H&E staining was used to quantify the neovascularization. Immunohistochemical staining was applied to quantify the CD34-positive stem cells and the fluorescence intensity of VEGF and TGF-β. Addition of LPCGF to autologous fat reduced the fat absorption by 5-15%, especially at the early stage, and no complications were observed. In addition, the effect was improved with increased CGF. Liquid phase concentrated growth factor improves autologous fat graft survival, and the most suitable ratio of LPCGF/fat is 1:8. LPCGF is rich in VEGF, TGF-β and CD34-positive stem cells, which can improve the fat transplantation effect, but the specific influence of a single component requires future evaluation. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Effect of Hyaluronidase on the Fat Graft.

Fat grafting has been widely used for facial rejuvenation and soft tissue reconstruction. However, it is associated with a lower retention rate than expected and complications such as fat necrosis or calcification. Several techniques that may increase the survival rate of fat grafts have been proposed. The techniques that promote the recipient sites vascularity to increase the survival rate of fat grafts include administration of growth factors, platelet- rich plasma, and adipose derived-stem cells or preconditioning of the recipient fat graft site. In this study, the authors evaluated the effect of hyaluronidase on autologous fat graft survival by pretreatment with hyaluronidase at the recipient site by using an animal model. In the experimental group, the recipient site of the fat graft was pretreated with hyaluronidase before fat grafting, whereas the control group was pretreated with normal saline. After 8 weeks of fat grafting, the average volume retention was 78.2% in the experimental group and 68.6% in control group. Considerable fibrosis between the fat globules in the control group was confirmed with Masson trichrome staining. CD31 immunofluorescence staining was performed and stained vessels were counted. Counted vessel number was significantly greater in the experimental group than in the control group. Pretreatment of hyaluronidase on the fat graft recipient site is a good option to enhance the outcome of the fat graft in the clinical setting.

Selected adipose-stem cell supplementation for promoting autologous fat graft survival in plastic surgery

Selected adipose-stem cell supplementation for promoting autologous fat graft survival in plastic surgery

Effects of Erythropoietin on Adipose Tissue

Background: The increased resorption and the difficulty of the fat graft take following autologous fat transplantation procedure are associated with reduced fat tissue revascularization and increased apoptosis of adipose cells. We suppose that the lipofilling procedure induces an inflammatory environment within the fat graft mass, whose evolution influences the efficacy of autologous fat graft survival. Erythropoietin (EPO) is a glycoprotein hormone known to exert angiogenetic and anti-inflammatory effects; therefore, our purpose was to investigate its reaction with adipose tissue used in lipofilling. Methods: Fat masses were harvested using manual suction lipectomy and then seeded on dishes in appropriate culture and treated for 3 weeks with 3 doses of EPO. CD31 and CD68 immunohistochemistry was used to identify microvessels and several infiltrating leukocyte cells. Results: Following EPO administration, we have detected an increase in the number of CD31-positive microvessel endothelium cells and CD31-positive small leukocytes and a reduction of CD68-positive cells. These effects were more conspicuous following higher EPO dose. Conclusions: Our findings evidence EPO treatment as a useful strategy to sustain the revascularization of grafted tissue and to reduce its inflammatory state.

Effects of erythropoietin on adipose tissue: a possible strategy in refilling.

Background:The increased resorption and the difficulty of the fat graft take following autologous fat transplantation procedure are associated with reduced fat tissue revascularization and increased apoptosis of adipose cells. We suppose that the lipofilling procedure induces an inflammatory environment within the fat graft mass, whose evolution influences the efficacy of autologous fat graft survival. Erythropoietin (EPO) is a glycoprotein hormone known to exert angiogenetic and anti-inflammatory effects; therefore, our purpose was to investigate its reaction with adipose tissue used in lipofilling.Methods:Fat masses were harvested using manual suction lipectomy and then seeded on dishes in appropriate culture and treated for 3 weeks with 3 doses of EPO. CD31 and CD68 immunohistochemistry was used to identify microvessels and several infiltrating leukocyte cells.Results:Following EPO administration, we have detected an increase in the number of CD31-positive microvessel endothelium cells and CD31-positive small leukocytes and a reduction of CD68-positive cells. These effects were more conspicuous following higher EPO dose.Conclusions:Our findings evidence EPO treatment as a useful strategy to sustain the revascularization of grafted tissue and to reduce its inflammatory state.

Alternatively activated M2 macrophages improve autologous Fat Graft survival in a mouse model through induction of angiogenesis.

Variability in graft retention with subsequent undercorrection remains a significant limitation of autologous fat grafting. The authors evaluated whether graft retention in a mouse model could be improved via graft supplementation with alternatively activated M2 macrophages, cells known to play a critical role in tissue repair. Grafts from C57BL/6 mouse inguinal fat pads were supplemented with M2 macrophages generated by intraperitoneal Brewer's thioglycollate injection and in vitro culture. Grafts with saline or M2 macrophages were injected under recipient mouse scalps and assessed by serial micro-computed tomographic analysis. Explanted grafts underwent immunohistochemical and flow cytometric analyses. M2 culture supernatants were added to stromal vascular fraction adipose-derived stem cells to assess adipogenic gene expression induction. One month after graft injection, no significant difference was noted between M2 macrophage-supplemented (105 ± 7.0 mm) and control graft volumes (72 ± 22 mm). By 3 months after injection, M2 macrophage-supplemented grafts remained stable, whereas controls experienced further volume loss (103 ± 8 mm versus 39.4 ± 15 mm; p = 0.015). Presence of macrophages in supplemented grafts was confirmed by flow cytometry. M2 macrophage-supplemented grafts exhibited a 157 percent increase in vascular density compared with controls (p < 0.05). Induction of adipogenic C/EBPα gene expression was observed with M2 supernatants addition to stromal vascular fraction adipose-derived stem cells. M2 macrophages improve autologous fat graft volume retention by stimulating angiogenesis. These findings provide proof-of-principle for development of fat grafting techniques that harness reparative properties of M2 macrophages.

Long‐term Survival of Autologous Fat Grafts into the Vocal Folds

Objectives: Determine whether long-term survival of fat implanted into the vocal folds is possible. Methods: Nine patients of those treated between 1992 and 2005 by means of bilateral fat injection into the vocal folds responded the call to assess long term results. Initial diagnosis was unilateral vocal fold palsy (6) and superficial sulcus (3). The graft was obtained by means of dissection of fat from the abdominal wall, and injected with an 18 G needle into the body of the vocal folds until 50% over correction was achieved. In palsy cases a higher fat volume was required on the paralyzed side. All patients underwent laryngostroboscopic examination preoperatively and postoperatively, along with postoperative magnetic resonance imaging (MRI) of the larynx, 4 to 14 years after surgery. As far as MRI is concerned, spine echo and fat-suppressed sequences in axial coronal and sagittal planes were obtained, looking for high intensity areas in T1-weighted images at the level of the vocal folds. Results: Laryngostroboscopy demonstrated permanent augmentation of the vocal folds with glottic closure improvement. MRI images in all cases showed the presence of enough fat in the body of the vocal folds, acting as support for good size and shape of the structure. Conclusions: Autologous fat cells injected into the vocal folds can survive years after surgery, acting as a permanent filler. Those conditions are in favor of fat grafts to be used as an inexpensive, easy to use, and long-lasting implant for selected cases of glottic incompetence.

Transplantation of rat adipose-derived stem cells (ASCs) to improve the survival of autologous aspirated fat grafts

Although autologous lipoaspirated fat grafting is now the most commonly used technique for soft tissue augmentation, problems, such as, unpredictability and a low rate of graft survival remain. The purpose of this study was to compare the long-term viabilities of aspirated fat grafts mixed with adipose-derived stem cells (ASCs; the experimental group) and aspirated fat grafts alone (the control group). Autologous aspirated fats were taken from the interscapular area and transplanted under scalp skin with or without ASCs. Remaining fat volumes were measured at 8 and 12 weeks after transplantation. Numbers of fat cells were randomly measured by hematoxylin and eosin staining. Mean autologous fat volumes in the experimental and control groups at week 8 were 0.410±0.040 ml and 0.418±0.043 ml, respectively, and at week 12 were 0.227±0.025 ml and 0.363±0.047 ml, respectively. Adding ASCs increased the survival rate of transplanted autologous fats at week 12 (p=0.006), and many new blood vessels formed in the outer layer of transplanted tissues by gross examination. H&E staining showed that the density of adipocytes in the experimental group was significantly higher than in the control group (p=0.033). The present study suggest that ASCs improve the survival of autologous fat grafts at 12 weeks after transplantation, which supports the notion that adding ASCs at time of lipotransfer helps maintain soft tissue augmentation.

An integrated approach for increasing the survival of autologous fat grafts in the treatment of contour defects: Har-Shai Y, Lindenbaum ES, Gamliel-La zarovich A, et al. Plast Reconstr Surg 104:945, 1999

An integrated approach for increasing the survival of autologous fat grafts in the treatment of contour defects: Har-Shai Y, Lindenbaum ES, Gamliel-La zarovich A, et al. Plast Reconstr Surg 104:945, 1999

An Integrated Approach for Increasing the Survival of Autologous Fat Grafts in the Treatment of Contour Defects

Autologous fat grafting as a technique to correct softtissue defects is a controversial subject. The high percentage of fat resorption and the resulting need for additional grafting considerably reduce the value of this method. The purpose of this study was to evaluate the clinical application of tissue-culturing methodology in the handling of the lipocyte aspirate in an endeavor to improve the survival rate and therefore the take of the grafted lipocytes. The method consists of syringe aspiration of the lipocytes from the donor site, isolation of intact lipocytes by gentle centrifugation, suspension of the aspirate in an enriched cell culture medium, and injection of the cell suspension into preformed subdermal tunnels. A number of media were tested and shown to prolong the survival of lipocytes ex vivo using fluorescent acridine orange stain. Implementing the integrated cell culture techniques increased the lipocytes' viability, as indicated in clinical evaluation in which the amount of graft take ranged between 50 and 90 percent. The results of 15 patients with varied types of cases who were operated on using this new methodology show that the tissue defect was filled and remained so in postoperative follow-ups of 6 to 24 months. A three-dimensional CAT scan-aided evaluation method was developed and used in one of four case histories presented herein. (Plast. Reconstr. Surg. 104: 945, 1999.)

Survival of autologous fat grafts in humans and in mice.

Autologous fat grafts have been used in a number of surgical procedures, yet properties of fat as a transplant material have remained unclear. This study was designed to compare experimental observations of subcutaneous fat grafts in mice with clinical observations of autologous fat grafts placed over the dura following laminectomy in humans. Subcutaneous fat grafts were observed daily in 75 CFl mice with the use of modified Algire back chambers. Grafts were examined histologically and histochemically at intervals up to 60 days after transplantation. Gross and microscopic observations suggest that fat grafts went through a period of initial breakdown of fat cells which was followed by revascularization. This resulted in normal appearing fat, although a smaller volume than the original graft. Three samples of autologous fat grafts from humans were removed during reoperation in the lumbar region up to 22 months after the original procedure. Histological examination revealed revascularized grafts reduced in size: the fat was normal and never replaced by scar tissue.