Fat Transplantation Research Articles

Autologous fat transplantation prior to permanent expander implant breast reconstruction enhances the outcome after two years: a randomized controlled trial.

Radiotherapy is important in breast cancer treatment. A side effect of the treatment is fibrosis that decreases the possibility for a successful breast reconstruction with expanders and with high patient satisfaction with the result. The most common option for mastectomized, irradiated women wishing for a breast reconstruction is autologous tissue transplantation. However, some patients are not suitable for flap surgery. Fifty mastectomized and irradiated women were included in a randomized controlled trial. They underwent breast reconstruction with expanders and were allocated 1:1 to either receive pre-treatment with autologous fat transplantation (AFT) or not. Primary outcomes were frequency of reoperations and complications. Secondary outcomes were number of days in hospital, number of outpatient visits to surgeon or nurse and patient reported outcome as reported with Breast Q. Follow-up time was 2 years. Fifty-two per cent of the intervention group and 68% of the controls underwent reoperations (p = 0.611). Thirty-two per cent of the intervention group and 52% of the controls had complications (p = 0.347). The median number of consultations with the nurse was four in the intervention group and six in the control group (p = 0.002). The AFT patients were significantly more satisfied with their breasts and psychosocial well-being after 2 years. They also had higher increase in satisfaction with breasts, psychosocial well-being, and sexual well-being when comparing baseline with 2 years postoperatively. This randomized controlled trial indicates benefits of AFT prior to breast reconstruction with expanders, especially on patient reported outcome even if the study sample is small.

Illuminating the shadows: an insight into periorbital hyperpigmentation

Periorbital hyperpigmentation (POH), also referred to as periorbital melanosis or dark eye circles, is a common dermatological concern characterized by darkening of the skin around the eyes. This review article aims to comprehensively analyze the current understanding of POH, encompassing its epidemiology, etiopathogenesis, clinical manifestations, diagnosis and available treatment modalities, and focusing on patients’ skin color. The review also consolidates a grading system for POH and emphasizes the importance of accurate diagnosis using clinical examination, assessment scores, Wood’s lamp, ultrasonography, and dermoscopy. Treatment modalities range from non-pharmacological measures to topical agents, including kojic acid, alpha-arbutin, vitamin C, vitamin E, niacinamide, retinoids, and hydrating agents. The manuscript explores the efficacy of various skin-lightening agents, such as hydroquinone, and introduces emerging treatments like caffeine, carotenoids, lactic acid, curcumin, and vitamin K. Additionally, it delves into procedural treatments like chemical peels, lasers, blepharopigmentation, mesotherapy, platelet-rich plasma therapy, fillers, autologous fat transplantation, and surgical interventions. The comprehensive approach to understanding and managing POH presented in this review aims to provide clinicians with valuable insights into the diverse therapeutic options available for this challenging cosmetic concern.

Correction of severe upper-eyelid sunken deformity in Asians by double-eyelid procedure and combination of orbital fat pad repositioning and autologous fat transplantation: a one-year follow-up study of 79 cases.

Nowadays, people's pace of life continues to rapid up, and many bad habits will accelerate the aging of the eye periphery, and patients with sunken upper eyelids are to be found in younger people. In young Asians, single eyelids are often accompanied by upper eyelid depression, so correcting the upper eyelid depression during blepharoplasty becomes a higher challenge for plastic surgeons. Current surgical methods for upper eyelid depression include three major categories: tissue repositioning, injection and filling, and combined use. According to grades 1 and 2 are mild or moderate upper eyelid sunken. The sunken can be well corrected only by repositioning the orbital fat pad, while the correction effect for severe upper eyelid sunken in grades 3 and 4 is Poor, need to be used in combination to achieve the desired effect. The authors sought to determine whether, for patients with single eyelids and severe upper eyelid depression of grades 3 and 4, combined with orbital fat pad repositioning and autologous fat transplantation during blepharoplasty, an aesthetic and youthful blepharoplasty can be achieved. This study included 79 patients with single eyelids and severe upper eyelid depression of grades 3 and 4 who received treatment between June 2020 and July 2022. All patients underwent double eyelid surgery plus orbital fat repositioning and autologous fat grafting. After a minimum follow-up period of 1 year, overall patient satisfaction was 92%. The recurrence rate within the first year was 6% and the complication rate was 5%. This combined surgery may be an option for young Asians with single eyelids and severe upper eyelid depression. In this study, the surgery resulted in natural-looking double eyelids and younger-looking eye sockets in most patients. A combination of different surgical methods based on the patient's preoperative condition is critical to achieving long-term correction.

Application of High-Frequency Ultrasound to Evaluate Forehead Filling Materials.

In recent years, soft tissue materials have been applied as forehead fillers. Some filling materials need to be removed or refilled in a timely manner in certain situations; therefore, it is important to develop a method to identify the location and type of filling materials. This study summarizes the imaging findings of different filling materials under high-frequency ultrasound, providing a reference for clinical treatment. We screened facial ultrasound images performed at the Plastic Surgery Hospital of the Chinese Academy of Medical Sciences from April 2015 to July 2023 and classified and summarized the types of frontal filling materials and their imaging results. This study included ultrasound imaging results from 114 patients, including 39 with hyaluronic acid (HA) filling, 45 with polyacrylamide hydrogel (PAG) filling, 14 who received autologous fat transplantation, 2 who received prosthesis implantation, 2 who received both HA and PAG filling, and 12 who received silicone oil filling. HA mainly manifests as an anechoic zone on ultrasonography, with images divisible into four types. PAG primarily presents as fine punctate echoes, divisible into five types. Fat transplantation presents as a low-echo area with uneven density, divisible into five types. Finally, the silicone oil-filling material appears as a cloud-like high echo on the forehead, visible throughout the entire skin layer, and unclear imaging in deep tissues. High-frequency ultrasound is a safe and reliable method to evaluate the type and position of forehead filling materials, which can be easily applied in clinical practice. This journal requires that authors assign a level of evidence to each article. 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 .

Transcutaneous lower eyelid blepharoplasty with micro-autologous fat transplantation harvested from orbital fat pads for lower eyelid aging treatment

The aging process of lower eyelids results in lower eyelid wrinkles, tear troughs, and eye bags. Many therapies have been described for treatment of lower eyelid aging, and transcutaneous blepharoplasty is often used for treating cases with eyebags and dermatochalasis. However, it may cause depression near the medial orbit resulting in a hollowed look. In the present study, we developed an innovative method transferring the herniated fatty tissue to volume loss area during the surgical procedure of transcutaneous lower eyelid blepharoplasty by means of micro-autologous fat transplantation harvested from resected orbital fat pads. Besides, we also analyze it efficacy and safety compared with traditional methods of transcutaneous lower eyelid blepharoplasty. We reviewed the records of the patients who underwent transcutaneous lower eyelid blepharoplasty with and without micro-autologous fat transplantation, for lower eyelid aging improvement. We used global aesthetic improvement scale, Hirmand's classification system, and Wrinkle Severity Rating Scale to evaluate the cosmetic outcome at 1week, 1month, and 3months after operation by two independent investigators. We found patients received transcutaneous lower eyelid blepharoplasty with autologous fat graft had significantly higher global aesthetic improvement scale and Wrinkle Severity Rating Scale improvement than those underwent transcutaneous lower eyelid blepharoplasty only in each evaluation timepoints. There was no significant difference of adverse effects between both surgical methods. The present study demonstrated the efficacy and safety of the lower eyelid blepharoplasty with micro-autologous fat transplantation harvesting from resected orbital fat pads.

Tracking Fat Grafts by Magnetic Resonance Imaging: A Comparative Study of Adolescent and Adult Patients with Stable Localized Scleroderma.

The optimal timing of reconstruction for patients with facial localized scleroderma is uncertain. The purpose of this study was to compare the outcomes of autologous fat transplantation in adolescent and adult patients with stable localized scleroderma. Adolescent (age 10-19 years) and adult (age >19 years) patients with no previous surgery were enrolled (n = 10, each group). Preoperative magnetic resonance imaging (MRI), blood tests and dermatological assessments were used for disease activity assessment. All patients underwent autologous fat transplantation for anatomic facial fat restoration with preoperative MRI planning. Preoperative, immediate and one-year postoperative 3D Dixon MRI scans with image registration and fusion techniques were used for fat graft tracking. Patient satisfaction was assessed with a 5-point Likert scale. There was no significant difference in sex, body mass index, disease severity, or volume of injected fat between the two groups (p > 0.05), except for age (p < 0.05). The one-year postoperative fat graft retention rate was not significantly different, with 36.6 ± 2.4% (ranging from 25.3 to 49.3%) in the adolescent group and 32.9 ± 1.7% (ranging from 27.3 to 40.1%) in the adult group (p > 0.05). Surgical outcomes were favorable in all patients, with satisfaction scores of 3.8 ± 0.2 points in the adolescent group and 3.6 ± 0.2 points in the adult group (p > 0.05). In stable localized scleroderma, the initial autologous fat transplantation was equally effective for facial contour deformity improvement, with no significant difference in fat graft retention or satisfaction.

Evaluation of autologous fat grafting in the treatment of juvenile localized scleroderma with facial involvement

Objectives: The objective of this study was to evaluate the effect of autologous fat grafting in patients with juvenile localized scleroderma with facial involvement. Methods: We retrospectively studied patients with juvenile localized scleroderma who were followed at the Hamburg Center for Pediatric and Adolescent Rheumatology at least 6 months post-operative follow-up and received at least one autologous fat transplantation for a facial lesion. Autologous fat grafting was conducted independent of disease-modifying treatment and/or disease activity. The effectiveness of the intervention was evaluated by assessing the immediate volume enhancement after injection of fat tissue compared with volume retained after 6 months. The volume enhancement was calculated from three-dimensional photo images analyzed in Mirror Medical Imaging Software, Canfield Scientific (New Jersey, USA). Results: Data of 22 juvenile patients were assessed from March 2006 to September 2021. In six patients, the photos could not be evaluated for the study. The median age of the remaining 16 patients at the beginning of the first fat graft was 8 years (range = 2.5–22 years). Patients underwent mean three interventions (range = 1–9). Evaluation of three-dimensional images showed that the volume retention at 6 months post autologous fat grafting is approximately 50%. The Modified Localized Scleroderma Skin Severity Index value did not correlate to volume changes at 6 months. In 4 of 16 patients, a decrease of the Localized Scleroderma Damage Index occurred. In all seven patients with cheek involvement, mean tragus-nose distance difference decreased (mean decrease 1.09 cm). We did not observe any significant clinical side effects. Conclusion: In this first bigger pediatric case series, the mean facial lesion volume increased around 50% after a mean of three interventions at 25 months of follow-up. No flares of the underlying disease were noted. Autologous fat grafting is a promising method to improve the cosmetic appearance of those patients.

Enhancing Fat Transplantation Efficiency in a Mouse Model through Pretreatment of Adipose-Derived Stem Cells with RIP3 Inhibitors.

Autologous fat transplantation, widely used in cosmetic and reparative surgery for volumetric enhancements, faces challenges with its inconsistent long-term survival rates. The technique's efficacy, crucial for its development, is hindered by unpredictable outcomes. Enriching fat grafts with adipose-derived stem cells (ADSCs) shows promise in improving survival efficiency. This study aimed to explore the potential of receptor-interacting protein kinase 3 (RIP3) kinase inhibitors as a pretreatment for ADSCs in enhancing autologous fat graft retention over a long term. ADSCs were isolated, cultured under normal or oxygen-glucose deprivation conditions, and mixed with particulate fat grafts to form distinct experimental groups in female nude mice. Fat graft mass and volume, along with underlying mechanisms, were evaluated using quantitative reverse transcription polymerase chain reaction (RT-qPCR), immunohistochemistry, and Western blot analysis. The experimental group, pretreated with RIP3 kinase inhibitors, had higher graft mass and volume, greater adipocyte integrity, and increased peroxisome proliferator-activated receptor gamma (PPARγ) mRNA levels than control groups. Furthermore, the experimental group demonstrated lower expression of necroptosis pathway proteins in the short term and an ameliorated inflammatory response as indicated by interleukin-1 beta (IL-1β), interleukin-10 (IL-10) mRNA levels, and histological analyses. Notably, enhanced neovascularization was evident in the experimental group. These findings suggest that RIP3 kinase inhibitor pretreatment of ADSCs can improve fat graft survival, promote adipocyte integrity, potentially decrease inflammation, and enhance neovascularization. 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 .

Identification and verification of AK4 as a protective immune-related biomarker in adipose-derived stem cells and breast cancer

BackgroundBreast cancer (BC) remains the most common cancer among women, and novel post-surgical reconstruction techniques, including autologous fat transplantation, have emerged. While Adipose-derived stem cells (ADSCs) are known to impact the viability of fat grafts, their influence on breast cancer progression remains unclear. This study aims to elucidate the genetic interplay between ADSCs and breast cancer, focusing on potential therapeutic targets. MethodsUsing the GEO and TCGA databases, we pinpointed differentially expressed (DE) mRNAs, miRNAs, lncRNAs, and pseudogenes of ADSCs and BC. We performed functional enrichment analysis and constructed protein-protein interaction (PPI), RNA binding protein (RBP)-pseudogene-mRNA, and lncRNA-miRNA-transcription factor (TF)-gene networks. Our study delved into the correlation of AK4 expression with 33 different malignancies and examined its impact on prognostic outcomes across a pan-cancer cohort. Additionally, we scrutinized immune infiltration, microsatellite instability, and tumor mutational burden, and conducted single-cell analysis to further understand the implications of AK4 expression. We identified novel sample subtypes based on hub genes using the ConsensusClusterPlus package and examined their association with immune infiltration. The random forest algorithm was used to screen DE mRNAs between subtypes to validate the powerful prognostic prediction ability of the artificial neural network. ResultsOur analysis identified 395 DE mRNAs, 3 DE miRNAs, 84 DE lncRNAs, and 26 DE pseudogenes associated with ADSCs and BC. Of these, 173 mRNAs were commonly regulated in both ADSCs and breast cancer, and 222 exhibited differential regulation. The PPI, RBP-pseudogene-mRNA, and lncRNA-miRNA-TF-gene networks suggested AK4 as a key regulator. Our findings support AK4 as a promising immune-related therapeutic target for a wide range of malignancies. We identified 14 characteristic genes based on the AK4-related cluster using the random forest algorithm. Our artificial neural network yielded excellent diagnostic performance in the testing cohort with AUC values of 0.994, 0.973, and 0.995, indicating its ability to distinguish between breast cancer and non-breast cancer cases. ConclusionsOur research sheds light on the dual role of ADSCs in BC at the genetic level and identifies AK4 as a key protective mRNA in breast cancer. We found that AK4 significantly predicts cancer prognosis and immunotherapy, indicating its potential as a therapeutic target.

Effect of high-density fat combined with adipose stem cell glue on the success rate of facial filling and its clinical value.

Facial fat grafting is a popular cosmetic procedure, and experts are increasingly endorsing the use of high-density fat with adipose stem cell glue for better results. This study aims to explore the effect of high-density fat combined with adipose stem cell glue on the success rate of facial filling and its clinical value. We conducted a randomized trial with 100 patients who underwent facial fat transplantation between August 2020 and August 2022. They were divided into two groups: a control group receiving traditional Coleman fat transplantation and an observation group receiving high-density fat with adipose stem cells. In the observation and control groups, the excellent and good rate was 98.00 and 80.00%. After 3 months of treatment, the thickness of frontal subcutaneous fat and temporal subcutaneous fat in the observation group was higher (P < 0.05). Observation group retention of fat transplantation was noticeably higher 3 months after treatment (P < 0.05). Three months after treatment, the VISIA (facial imaging system) scores of facial color spots, facial pores and facial wrinkles in the observation group were lower (P < 0.05). After treatment, both groups indicated noticeable improvements in physiological functions, health status, social function, mental health, and somatic diseases compared to before treatment. Notably, the observation group had higher scores (P < 0.05). The observation group had a lower complication rate (4.00% vs. 22.00%) and higher satisfaction rate (98.00% vs. 86.00%) than the control group. Using high-density fat combined with adipose stem cell glue for facial fat grafting yields superior results, reduces complications, and boosts patient satisfaction compared to traditional methods. We have complied with all relevant ethical regulations with regard to the use of stem cells.

Autologous Fat Transfer in Craniofacial Surgery

Over the past two decades, autologous fat transfer has garnered significant recognition and widespread adoption within esthetic and reconstructive surgical domains. In craniofacial surgery, fat transplantation is frequently employed to address soft tissue volumetric deficiencies and asymmetries that influence facial contours. While adipose tissue (AT) is widely regarded as an optimal choice for augmentation due to its abundant availability and biocompatibility, the unpredictability and heightened resorption rates observed with traditional lipofilling techniques present a challenge for clinicians. Adipose-derived stem cells (ASCs) housed within the grafted tissue play a pivotal role in graft survival and offer avenues for tissue repair due to their angiogenic, anti-inflammatory, and immunosuppressive properties. Micro Fragmentation of Adipose Tissue (MFAT), utilized in several FDA-approved processing devices, has demonstrated promising outcomes in treating osteoarthritic joints, with success primarily attributed to enhanced paracrine function of ASCs via preservation of the perivascular niche. Currently, its application for treating bone or articular defects in the craniofacial region, including abnormalities of the temporomandibular joint, remains limited. This scarcity underscores the need for further investigation prior to its widespread integration into clinical practice.

Abstract B091: Mechanisms underlying the omental support of ovarian cancer peritoneal metastasis

Abstract More than 80% of ovarian cancer (OC) cases have metastasized to the peritoneal cavity at diagnosis. The five-year survival rate for these patients is 25%. Within the peritoneal cavity, the most common and early site of metastasis is the omentum, a well-vascularized, specialized adipose tissue that arises off the greater curvature of the stomach. Because OC homes to the omentum, it is removed as a standard of care for patients with peritoneal metastases. In mouse models, the omentum is also an early metastatic site, and omentectomy reduces tumor expansion. The mechanism by which the omentum promotes OC growth is unknown, perhaps due to the complex omental microenvironment. The omentum contains many features that could impact OC seeding. It is covered by a mesothelial lining that extends in a sheet anchoring the omentum to surrounding tissues and is highly perfused by blood vessels. It contains lymphoid aggregates or milky spots that may contribute to pro- and anti-tumor immunity. This study explores the association of OC metastases with specific omentum features. We intraperitoneally injected luciferase-expressing ID8 OC cells to mimic high-grade serous OC metastasis. Using high-resolution, spatial ex vivo bioluminescence imaging (BLI), we found that tumor nodules preferentially formed in adipocyte-rich regions of the omentum and the mesentery, another peritoneal tissue favorable for OC seeding. To determine whether adipocytes, the most abundant omental cell type, are the primary support of OC, we crossed Adiponectin Cre+ and DTA mice to generate mice lacking white and brown adipocytes from birth. To overcome the metabolic syndrome the fatless mice develop, they receive subcutaneous fat transplants dorsally, referred to as distal adipocyte rescue of lipodystrophy (DARL) mice. Littermate controls receive sham surgeries. The blood triglyceride, glucose, and insulin levels are normalized post-transplant. Thus, the peritoneal cavity lacks mature adipocytes, but the mice have typical metabolic profiles, allowing us to study the role of omental adipocytes in peritoneal metastasis. Once the mice recovered from surgery, they were intraperitoneally injected with luciferase-expressing ID8s. While it was hypothesized that OC metastatic seeding within the adipocyte-free omentum and associated peritoneum would be impaired without local mature adipocytes, BLI revealed that the tumor burden was not decreased in DARL mice. Notably, specific regions of OC seeding, where mature adipocytes would have localized if present, such as the omentum and mesentery, retained tumor nodules in DARL mice. This conserved OC localization suggests that other cells in this specific microenvironment might be responsible for metastatic spread. To identify these cells, studies are ongoing to profile these regions in the DARL and control mice via flow cytometry and single-cell RNA sequencing. By unraveling the support for OC cells in the omentum, therapeutic strategies can be identified to repolarize the metastatic milieu and halt further spread to improve patient outcomes. Citation Format: Rachel Mintz, Alexandre Gallerand, Jichang Han, Sarah Ning, Wei Zou, Mary Wohltmann, Bernd Zinselmeyer, Gwendalyn Randolph. Mechanisms underlying the omental support of ovarian cancer peritoneal metastasis [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B091.

Lipolysis inhibition improves the survival of fat grafts through ameliorating lipotoxicity and inflammation.

Fat grafting is a promising technique for correcting soft tissue abnormalities, but oil cyst formation and graft fibrosis frequently impede the therapeutic benefit of fat grafting. The lipolysis of released oil droplets after grafting may make the inflammation and fibrosis in the grafts worse; therefore, by regulating adipose triglyceride lipase (ATGL) via Atglistatin (ATG) and Forskolin (FSK), we investigated the impact of lipolysis on fat grafts in this study. After being removed from the mice and chopped into small pieces, the subcutaneous fat from wild-type C57BL/6J mice was placed in three different solutions for two hours: serum-free cell culture medium, culture medium+FSK (50 μM), and culture medium+ATG (100 μM). Following centrifugation to remove water and free oil droplets, 0.3 mL of the fat particles per mouse was subcutaneously injected into the back of mice. Additionally, the subcutaneous fat grafting area was immediately injected with PBS (control group), ATG (30 mg/kg), and FSK (15 mg/kg) following fat transplantation. Detailed cellular events after grafting were investigated by histological staining, real-time polymerase chain reaction, immunohistochemistry/immunofluorescent staining, and quantification. Two weeks after grafting, grafts treated with ATG showed lower expression of ATGL and decreased mRNA levels of TNFα and IL-6. In contrast, grafts treated with ATG showed elevated expression levels of IL-4 and IL-13 compared to the control grafts. In addition, fewer apoptotic cells and oil cysts were observed in ATG grafts. Meanwhile, a higher CD206+/CD68+ ratio of macrophages and more CD31+ vascular endothelial cells existed in the 2-month ATG grafts. In comparison to the control, ATG treatment improved the volume retention of grafts, and decreased graft fibrosis and oil cyst formation. By preventing oil droplet lipolysis, pharmacological suppression of ATGL shielded adipocytes from lipotoxicity following grafting. Additionally, ATG ameliorated the apoptosis and inflammation brought on by adipocyte death and oil droplet lipolysis in grafted fat. These all indicate that lipolysis inhibition improved transplanted fat survival and decreased the development of oil cysts and graft fibrosis, offering a potential postoperative pharmacological intervention for bettering fat grafting.

Progress of Degradable Synthetic Polymers in Adipose Tissue Engineering-A Review

Breast cancer stands as the foremost prevalent malignancy affecting women worldwide. The restoration of soft tissue volume is often necessary in cases of soft tissue loss, such as burn defects, surgical area defects, or posttumor resection defects, particularly in breast cancers. Conventional surgeries interventions, such as flap transplantation, can result in various complications and malformations, while prosthesis implantation may not be suitable due to skin weakness caused by radiation therapy. Autologous fat transplantation to the breast exhibits limited efficacy due to the unpredictable of resorption and low graft survival rates. Tissue engineering has emerged as a promising field offering novel therapeutic possibilities in regenerative medicine over the past two decades. Extensive exploration has been conducted on synthetic materials for adipose tissue engineering applications. This review delineates the current advancements and future directions in adipose tissue engineering strategies, cell applications, adipogenesismechanisms, and key factors, while focusing on the utilization of degradable synthetic polymers and the integration of 3D printing technologies.

Exploring Preclinical Experiments with Different Fat Types for Autologous Fat Grafting.

Autologous fat transplantation has been a cornerstone of tissue regeneration for decades. However, there is no standardized selection system or criteria for fat graft selection, often relying heavily on the surgeon's experience. This study aimed to investigate various types of fat derivatives, both in vitro and in vivo at the same condition. We collected traditional fat granules of different sizes and SVF-gel, evaluating the viability of ADSCs isolated from them and their performance after grafting into mice. Large fat granules exhibited more complete adipocyte structures, and the isolated ADSCs demonstrated superior differentiation, proliferation, and secretion capacities. They also showed excellent volume retention after 12 weeks. In contrast, ADSCs isolated from SVF-gel displayed lower vitality. However, grafts from SVF-gel exhibited the highest volume maintenance rate among the four groups after 12 weeks, closely resembling normal adipose tissue and displaying significant vascularization. Compared to large fat granule and SVF-gel group, medium and small fat granule grafts exhibited lower volume retention and less angiogenesis. Through preclinical studies, the flexible clinical use of different fat grafts can be tailored to their unique characteristics. This journal requires that authors assign a level of evidence to each article. 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 Evolving Function of Vasculature and Pro-angiogenic Therapy in Fat Grafting.

Autologous fat grating is a widely-accepted method to correct soft tissue deficiency. Although fat transplantation shows excellent biocompatibility and simple applicability, the relatively low retention rate caused by fat necrosis is still a challenge. The vasculature is integral after fat grafting, serving multiple crucial functions. Rapid and effective angiogenesis within grafts is essential for supplying oxygen necessary for adipocytes' survival. It facilitates the influx of inflammatory cells to remove necrotic adipocytes and aids in the delivery of regenerative cells for adipose tissue regeneration in fat grafts. The vasculature also provides a niche for interaction between adipose progenitor cells and vascular progenitor cells, enhancing angiogenesis and adipogenesis in grafts. Various methods, such as enriching grafts with diverse pro-angiogenic cells or utilizing cell-free approaches, have been employed to enhance angiogenesis. Beige and dedifferentiated adipocytes in grafts could increase vessel density. This review aims to outline the function of vasculature in fat grafting and discuss different cell or cell-free approaches that can enhance angiogenesis following fat grafting.

Exploring Superselective Intraarterial Thrombolysis for Autologous Fat Injection-Induced Vision Loss.

Intravascular injection represents the most severe complication in fat transplantation procedures. Currently, the prognosis for patients who suffer from blindness due to fat transplantation-induced ocular vascular occlusion is far from optimistic. The aim of this study was to explore and evaluate the efficacy and safety of arterial thrombolysis in the treatment of ocular vascular occlusion caused by fat transplantation. We analyzed the data of 12 patients who underwent intraarterial thrombolysis and conservative treatments for facial autologous fat grafting-associated ocular vascular occlusion. Among the cases, there were 6 instances of ophthalmic artery embolism and 6 cases of central retinal artery occlusion. All patients suffered with sudden blindness, sometimes accompanied by eye pain, ptosis, strabismus, skin necrosis at the injection site, or cerebral microinfarction. They received symptomatic conservative treatments and intraarterial thrombolysis, encompassing mechanical vessel recanalization, vessel dilation, and dissolution of thrombus constituents. Following intraarterial thrombolysis, a noteworthy improvement in the blood flow of both the main trunk and peripheral branches of the ophthalmic artery was observed in the majority of patients when contrasted with their pretreatment status. One patient experienced a headache intraoperatively, while no significant discomfort was reported by the remaining patients. After conservative treatments and intraarterial thrombolysis, all patients experienced improvement in ocular symptoms, skin necrosis, and cerebral infarction. Three patients demonstrated improvement in visual acuity. These patients had surpassed the recommended time window for treatment, yet the occlusion of the ophthalmic artery was not complete. Intraarterial thrombolysis combined with conservative treatments achieves early perfusion and is expected to promote visual recovery. Hospitals that possess the necessary treatment capabilities are encouraged to establish this therapeutic pathway.

Adipose-derived stem cell exosomes promote tumor characterization and immunosuppressive microenvironment in breast cancer

Adipose-derived stem cells (ASC) or autologous fat transplantation could be used to ameliorate breast cancer postoperative deformities. This study aims to explore the action of ASC and ASC-exosomes (ASC-exos) in breast cancer characterization and tumor microenvironment immunity, which provided a new method into the application of ASC-exos. ASC were extracted from human adipose tissue for the isolation and verification of ASC-exos. ASC-exos were co-cultured with CD4+T cells, CD14+ monocytes and MCF-7 cells, respectively. The tumor formation of nude mice was also constructed. Cell characterization was determined by CCK8, scratch assay, and Transwell. Hematoxylin–eosin (HE), immunohistochemistry (IHC) and immunofluorescence (IF) staining were used to observe the histopathology and protein expression. CD4+T cell and CD14+ monocytes differentiation was detected by flow cytometry. Western blot, qRT-PCR and RNAseq were used to detect the action of ASC-exos on gene and protein expression. CD4+T cells could take up ASC-exos. ASC-exos inhibited Th1 and Th17 differentiation and promoted Treg differentiation of CD4+T cells. ASC-exos inhibited M1 differentiation and promoted M2 differentiation of CD14+ monocytes. ASC-exos promoted the migration, proliferation, and invasion, while inhibited apoptosis of MCF-7 cells. ASC-exos promoted the tumor formation of breast cancer. The effect of ASC-exos on tumor microenvironment immunity was in accordance with the above in vitro results. TOX, CD4 and LYZ1 genes were upregulated, while Mettl7b and Serpinb2 genes were downregulated in ASC-exos group. Human T-cell leukemia virus 1 infection pathway was significantly enriched in ASC-exos. Thus, ASC-exos promoted breast cancer characterization and tumor microenvironment immunosuppression by regulating macrophage and T cell differentiation.

P029 Loss of adipose tissue protects mice from intestinal inflammation

Abstract Background Crohn’s disease (CD) is associated with creeping fat, characterized by hyperplasia of mesenteric adipocytes and increased secretion of various adipokines, including leptin. Leptin can promote intestinal inflammation by inducing pro-inflammatory cytokines such as TNFα in murine and human lymphocytes. Recent meta-analyses have shown that increased body mass index (BMI) increases the risk of developing CD. However, whether the surgical removal of mesenteric fat could improve the outcome of CD patients and the impact of fat-derived signals on intestinal autoimmunity remain elusive. Methods To decipher the role of adipose tissue in the regulation of intestinal autoimmunity, we investigated here how the absence of adipose tissue affects epithelial barrier functions and immune cell homeostasis. Therefore, we studied lipoatrophic Ppargfl/fl-Adipoq-Cre mice, that completely lack adipose tissue, under steady-state conditions and after induction of chronic dextran sodium sulfate (DSS)-mediated inflammation, as well as in allogeneic fat transplantation models. We characterized our models using flow cytometry, RNA sequencing, immunohistochemistry, western blot analyses, ELISA and calcium measurements. Results At steady state, lipoatrophic mice showed a decrease in CD4 IL-17+ T cells in the ileum, and lower frequencies of CD8 T cells and CD4 FoxP3+ cells in the colon, suggesting that fat-derived signals are required for proper T cell homeostasis in mice. To understand how the absence of adipose tissue affects the severity of intestinal inflammation, we challenged lipoatrophic or WT littermates with 3 cycles of 1.5% DSS, which induced weight loss in both WT and lipoatrophic mice. However, only fat-proficient WT mice developed severe colitis, whereas lipoatrophic animals had significantly reduced intestinal inflammation and displayed disturbances in the differentiation and function of pro-inflammatory T cells including Th1 and Th17 cells. Importantly, these defects in T cell function could be rescued by allogeneic transplantation of adipose tissue from lean wild-type mice but not by adipose tissue from leptin-deficient ob/ob mice, highlighting that the role of the adiopokine leptin as an important pro-inflammatory factor in IBD. Conclusion Taken together, our data demonstrate that adipose tissue acts as an important regulator of intestinal autoimmunity by controlling the differentiation and function of pro-inflammatory T cells through the secretion of adipokines including leptin. We believe that these observations may help explain why obese individuals with higher BMI may be at a higher risk of developing intestinal inflammation and Crohn’s disease.

Dual Network Hydrogels Based on PRP and SA Promote the Retention Rate and Vascularization of Transplanted Fat.

Autologous adipose tissue often experiences ischemia and hypoxia after transplantation, leading to low retention rates and unstable operative impacts due to necrotic absorption. Platelet-rich plasma (PRP) can enhance fat regeneration and increase the fat retention rate after transplantation. However, the quick release of growth factors (GFs) in PRP decreases therapeutic efficiency. This study aimed to achieve a slow release of PRP to promote fat retention. We prepared a dual-network hydrogel (DN gel) based on FDA-approved PRP and sodium alginate (SA) through a simple "one-step" activation process. In vivo study, adipose tissue with saline (control group), SA gel (SA gel group), PRP gel (PRP gel group), and DN gel (DN gel group) was injected subcutaneously into the dorsum of nude mice. At 4 and 12 weeks after injection, tissues were assessed for volume and weight. Hematoxylin and eosin staining (HE) and immunofluorescence staining were performed for histological assessment. DN gel exhibits long-lasting growth factor effects, surpassing conventional clinical PRP gel regarding vascularization potential. In fat transplantation experiments, DN gel demonstrated improved vascularization of transplanted fat and increased retention rates, showing promise for clinical applications. DN gel-assisted lipofilling can significantly improve the retention rate and quality of transplanted fat. DN gel-assisted lipofilling, which is considered convenient, is a promising technique to improve neovascularization and fat survival. 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.