Cytokine production by bovine adipose tissue stromal vascular fraction cells upon Neospora caninum stimulation.

In bovines few studies addressed the contribution of adipose tissue to the host immune response to infection. Here we evaluated the in vitro response of bovine adipose tissue stromal vascular fraction (SVF) cells to the protozoan parasite Neospora caninum, using live and freeze-killed tachyzoites. Live N. caninum induced the production of IL-6, IL-1ß and IL-10 by SVF cells isolated from subcutaneous adipose tissue (SAT), while in mesenteric adipose tissue (MAT) SVF cell cultures only IL-1ß and IL-10 production was increased, showing slight distinct responses between adipose tissue depots. Whereas a clear IL-8 increase was detected in peripheral blood leucocytes (PBL) culture supernatants in response to live N. caninum, no such increase was observed in SAT or MAT SVF cell cultures. Nevertheless, in response to LPS, increased IL-8 levels were detected in all cell cultures. IL-10 levels were always increased in response to stimulation (live, freeze-killed N. caninum and LPS). Overall, our results show that bovine adipose tissue SVF cells produce cytokines in response to N. caninum and can therefore be putative contributors to the host immune response against this parasite.

A pedicled buccal periosteal flap for the closure of oro-antral fistula.

BACKGROUND: An oroantral fistula is a communication between the maxillary antrum and oral cavity. This pathological communication is formed mainly due to dental extraction of maxillary premolars and molars. Adequate management should include closing the oroantral fistula and eliminating sinus infections to prevent recurrence and sinusitis. PURPOSE: This study aimed to evaluate the effectiveness of using the pedicled buccal periosteal flap for closing an oroantral fistula without changing the native intraoral structure. PATIENTS & METHODS: Patients with oroantral fistulas were included in this study. The patients were examined clinically by Valsalva test and cheek-blowing test, the hole was probed, and the extent of the underlying bone defect was determined radiographically using computed tomography preoperatively. All patients underwent surgical closure of oroantral fistula using a pedicled buccal periosteal flap. RESULTS: All 10 patients obtained satisfactory results with marked improvement in the function of the maxillary sinus and complete healing of oroantral fistula with no recurrence except in Case No. 5, who had a recurrence of the oroantral fistula, also there was no statistically significant difference between the vestibular depth preoperatively and postoperatively. CONCLUSION: A pedicled buccal periosteal flap is a novel technique for oroantral fistula closure as it preserves vestibular depth with a tension-free closure flap and harbors the advantages of the regenerative potential of the periosteum. REGISTRATION DATE: 14/8/2023 REGISTRATION NUMBER: NCT05987943.

Do Muscle Mass and Body Fat Differ Between Elite and Amateur Natural Physique Athletes on Competition Day? A Preliminary, Cross-Sectional, Anthropometric Study.

ABSTRACT: González-Cano, H, Martín-Olmedo, JJ, Baz-Valle, E, Contreras, C, Schoenfeld, BJ, García-Ramos, A, Jiménez-Martínez, P, and Alix-Fages, C. Do muscle mass and body fat differ between elite and amateur natural physique athletes on competition day? A preliminary, cross-sectional, anthropometric study. J Strength Cond Res 38(5): 951-956, 2024-Natural physique athletes strive to achieve low body fat levels while promoting muscle mass hypertrophy for competition day. This study aimed to compare the anthropometric characteristics of natural amateur (AMA) and professional (PRO) World Natural Bodybuilding Federation (WNBF) competitors. Eleven male natural physique athletes (6 PRO and 5 AMA; age = 24.8 ± 2.3 years) underwent a comprehensive anthropometric evaluation following the International Society for the Advancement of Kinanthropometry protocol within a 24-hour time frame surrounding the competition. The 5-component fractionation method was used to obtain the body composition profile of the muscle, adipose, bone, skin, and residual tissues. Five physique athletes exceeded the 5.2 cutoff point of muscle-to-bone ratio (MBR) for natural athletes. Professional physique athletes were older than AMA physique athletes (p = 0.05), and they also presented larger thigh girths (p = 0.005) and bone mass (p = 0.019) compared with AMA physique athletes. Although no statistically significant between-group differences were observed in body mass, height, or body fat levels, PRO physique athletes exhibited a higher body mass index (BMI; AMA: 24.45 ± 0.12; PRO: 25.52 ± 1.01; p = 0.048), lean body mass (LBM; AMA: 64.49 ± 2.35; PRO: 69.80 ± 3.78; p = 0.024), fat-free mass (FFM; AMA: 71.23 ± 3.21; PRO: 76.52 ± 4.31; p = 0.05), LBM index (LBMI; AMA: 20.65 ± 0.52; PRO: 21.74 ± 0.85; p = 0.034), and fat-free mass index index (FFMI; AMA: 22.80 ± 0.22; PRO: 23.83 ± 0.90; p = 0.037) compared with AMA physique athletes. These findings highlight the unique characteristics and anthropometric differences between PRO and AMA natural physique athletes on competition day, emphasizing the significance of age, thigh girth, bone mass, BMI, LBM, FFM, and FFMI in distinguishing these 2 groups. Based on our findings, the established boundaries for muscle mass in natural physique athletes, based on FFMI and MBR, warrant reconsideration.

Evaluation of the effects of adding an adipose tissue-derived stromal vascular fraction to platelet-rich plasma injection in the treatment of androgenetic alopecia: A randomized clinical trial.

BACKGROUND: Stromal vascular fraction (SVF) cells derived from adipose tissue and platelet-rich plasma (PRP) are among novel treatments for androgenetic alopecia (AGA). We aimed to investigate the effect of adding SVF to PRP and compare it to administering PRP injection alone. METHODS: Eighteen patients were randomly divided into two groups of nine. The PRP group was treated with PRP at all three visits at 1-month intervals, while the SVF-PRP group received an SVF injection on the first visit and a PRP injection on the second and third visits. Each group was evaluated at baseline and 20 weeks after the therapy's initiation. RESULTS: Changes in mean hair diameter and hair count compared to baseline were significant in both groups. The PRP group experienced a greater increase in mean hair count than the SVF-PRP group, and the SVF-PRP group had a marginally greater increase in hair diameter than the PRP group. These differences were not statistically significant compared to each other. The patient and physician assessment scores exceeded the mean (on a scale from 0: poor to 3: excellent) in both groups. CONCLUSION: Adding one SVF injection to two PRP treatment sessions versus three PRP injections alone had no significant difference in evaluated variables. If additional research demonstrates the same results, we suggest that multiple SVF injection sessions may be required to produce a statistically significant difference compared to PRP injection alone. Moreover, considering lower cost and greater accessibility of PRP, it can be used before SVF in the treatment of AGA.

Elexacaftor/tezacaftor/ivacaftor influences body composition in adults with cystic fibrosis: a fully automated CT-based analysis.

A poor nutritional status is associated with worse pulmonary function and survival in people with cystic fibrosis (pwCF). CF transmembrane conductance regulator modulators can improve pulmonary function and body weight, but more data is needed to evaluate its effects on body composition. In this retrospective study, a pre-trained deep-learning network was used to perform a fully automated body composition analysis on chest CTs from 66 adult pwCF before and after receiving elexacaftor/tezacaftor/ivacaftor (ETI) therapy. Muscle and adipose tissues were quantified and divided by bone volume to obtain body size-adjusted ratios. After receiving ETI therapy, marked increases were observed in all adipose tissue ratios among pwCF, including the total adipose tissue ratio (+ 46.21%, p < 0.001). In contrast, only small, but statistically significant increases of the muscle ratio were measured in the overall study population (+ 1.63%, p = 0.008). Study participants who were initially categorized as underweight experienced more pronounced effects on total adipose tissue ratio (p = 0.002), while gains in muscle ratio were equally distributed across BMI categories (p = 0.832). Our findings suggest that ETI therapy primarily affects adipose tissues, not muscle tissue, in adults with CF. These effects are primarily observed among pwCF who were initially underweight. Our findings may have implications for the future nutritional management of pwCF.

Enhanced potent immunosuppression of intracellular adipose tissue-derived stem cell extract by priming with three-dimensional spheroid formation.

Immunomodulatory properties of mesenchymal stem cells are widely studied, supporting the use of MSCs as cell-based therapy in immunological diseases. This study aims to generate cell-free MSC extract and improves their immunomodulatory potential. Intracellular extracts were prepared from adipose-derived stem cells (ADSC) spheroid via a freeze-thawing method. The immunomodulatory capacities of ADSC spheroid extracts were investigated in vitro, including lymphocyte proliferation, T regulatory cell expansion, and macrophage assays. A comparative study was conducted with ADSC monolayer extract. The key immunomodulatory mediators presented in ADSC extract were identified. The results revealed that ADSC spheroid extract could suppress lymphocyte activation while enhancing T regulatory cell expansion. Immunomodulatory molecules such as COX-2, TSG-6, and TGF-ß1 were upregulated in ADSC priming via spheroid culture. Selective inhibition of COX-2 abrogates the effect of ADSC extract on inducing T regulatory cell expansion. Thus, ADSC spheroid extract gains high efficacy in regulating the immune responses which are associated in part by COX-2 generation. Furthermore, ADSC spheroid extract possessed a potent anti-inflammation by manipulation of TNF-α production from LPS-activated macrophage. Our current study has highlighted the opportunity of using cell-free extracts from adipose tissue-derived mesenchymal stem cells spheroid as novel immunomodulators for the treatment of immunological-associated diseases.

The extracts of osteoblast developed from adipose-derived stem cell and its role in osteogenesis.

Cell-based therapy has become an achievable choice in regenerative medicines, particularly for musculoskeletal disorders. Adipose-derived stem cells (ASCs) are an outstanding resource because of their ability and functions. Nevertheless, the use of cells for treatment comes with difficulties in operation and safety. The immunological barrier is also a major limitation of cell therapy, which can lead to unexpected results. Cell-derived products, such as cell extracts, have gained a lot of attention to overcome these limitations. The goal of this study was to optimize the production of ASC-osteoblast extracts as well as their involvement in osteogenesis. The extracts were prepared using a freeze-thaw method with varying temperatures and durations. Overall, osteogenic-associated proteins and osteoinductive potential of the extracts prepared from the osteogenic-induced ASCs were assessed. Our results demonstrated that the freeze-thaw approach is practicable for cell extracts production, with minor differences in temperature and duration having no effect on protein concentration. The ASC-osteoblast extracts contain a significant level of essential specialized proteins that promote osteogenicity. Hence, the freeze-thaw method is applicable for extract preparation and ASC-osteoblast extracts may be beneficial as an optional facilitating biologics in bone anabolic treatment and bone regeneration.

Exploring Anti-Fibrotic Effects of Adipose-Derived Stem Cells: Transcriptome Analysis upon Fibrotic, Inflammatory, and Hypoxic Conditioning.

Autologous fat transfers show promise in treating fibrotic skin diseases, reversing scarring and stiffness, and improving quality of life. Adipose-derived stem cells (ADSCs) within these grafts are believed to be crucial for this effect, particularly their secreted factors, though the specific mechanisms remain unclear. This study investigates transcriptomic changes in ADSCs after in vitro fibrotic, inflammatory, and hypoxic conditioning. High-throughput gene expression assays were conducted on ADSCs exposed to IL1-ß, TGF-ß1, and hypoxia and in media with fetal bovine serum (FBS). Flow cytometry characterized the ADSCs. RNA-Seq analysis revealed distinct gene expression patterns between the conditions. FBS upregulated pathways were related to the cell cycle, replication, wound healing, and ossification. IL1-ß induced immunomodulatory pathways, including granulocyte chemotaxis and cytokine production. TGF-ß1 treatment upregulated wound healing and muscle tissue development pathways. Hypoxia led to the downregulation of mitochondria and cellular activity.

The Efficacy of Fat Grafting on Treating Post-Mastectomy Pain with and without Breast Reconstruction: A Systematic Review and Meta-Analysis.

Post-mastectomy pain syndrome (PMPS), characterized by persistent pain lasting at least three months following mastectomy, affects 20-50% of breast surgery patients, lacking effective treatment options. A review was conducted utilizing EMBASE, MEDLINE, and all evidence-based medicine reviews to evaluate the effect of fat grafting as a treatment option for PMPS from database inception to 29 April 2023 (PROSPERO ID: CRD42023422627). Nine studies and 812 patients in total were included in the review. The overall mean change in visual analog scale (VAS) was -3.6 in 285 patients following fat grafting and 0.5 in 147 control group patients. There was a significant reduction in VAS from baseline in the fat grafting group compared to the control group, n = 395, mean difference = -2.17 (95% CI, -2.95 to -1.39). This significant improvement was also noted in patients who underwent mastectomy without reconstruction. Common complications related to fat grafting include capsular contracture, seroma, hematoma, and infection. Surgeons should consider fat grafting as a treatment option for PMPS. However, future research is needed to substantiate this evidence and to identify timing, volume of fat grafting, and which patient cohort will benefit the most.

Polyphenols: immunonutrients tipping the balance of immunometabolism in chronic diseases.

Mounting evidence progressively appreciates the vital interplay between immunity and metabolism in a wide array of immunometabolic chronic disorders, both autoimmune and non-autoimmune mediated. The immune system regulates the functioning of cellular metabolism within organs like the brain, pancreas and/or adipose tissue by sensing and adapting to fluctuations in the microenvironment's nutrients, thereby reshaping metabolic pathways that greatly impact a pro- or anti-inflammatory immunophenotype. While it is agreed that the immune system relies on an adequate nutritional status to function properly, we are only just starting to understand how the supply of single or combined nutrients, all of them termed immunonutrients, can steer immune cells towards a less inflamed, tolerogenic immunophenotype. Polyphenols, a class of secondary metabolites abundant in Mediterranean foods, are pharmacologically active natural products with outstanding immunomodulatory actions. Upon binding to a range of receptors highly expressed in immune cells (e.g. AhR, RAR, RLR), they act in immunometabolic pathways through a mitochondria-centered multi-modal approach. First, polyphenols activate nutrient sensing via stress-response pathways, essential for immune responses. Second, they regulate mammalian target of rapamycin (mTOR)/AMP-activated protein kinase (AMPK) balance in immune cells and are well-tolerated caloric restriction mimetics. Third, polyphenols interfere with the assembly of NLR family pyrin domain containing 3 (NLRP3) in endoplasmic reticulum-mitochondria contact sites, inhibiting its activation while improving mitochondrial biogenesis and autophagosome-lysosome fusion. Finally, polyphenols impact chromatin remodeling and coordinates both epigenetic and metabolic reprogramming. This work moves beyond the well-documented antioxidant properties of polyphenols, offering new insights into the multifaceted nature of these compounds. It proposes a mechanistical appraisal on the regulatory pathways through which polyphenols modulate the immune response, thereby alleviating chronic low-grade inflammation. Furthermore, it draws parallels between pharmacological interventions and polyphenol-based immunonutrition in their modes of immunomodulation across a wide spectrum of socioeconomically impactful immunometabolic diseases such as Multiple Sclerosis, Diabetes (type 1 and 2) or even Alzheimer's disease. Lastly, it discusses the existing challenges that thwart the translation of polyphenols-based immunonutritional interventions into long-term clinical studies. Overcoming these limitations will undoubtedly pave the way for improving precision nutrition protocols and provide personalized guidance on tailored polyphenol-based immunonutrition plans.

Association of seasonal changes in circulating cortisol concentrations with the expression of cortisol biosynthetic enzymes and a glucocorticoid receptor in the blubber of common bottlenose dolphin.

Cortisol is secreted from the adrenal cortex in response to stress, and its circulating levels are used as robust physiological indicators of stress intensity in various animals. Cortisol is also produced locally in adipose tissue by the conversion of steroid hormones such as cortisone, which is related to fat accumulation. Circulating cortisol levels, probably induced by cold stress, increase in cetaceans under cold conditions. However, whether cortisol production in subcutaneous adipose tissue is enhanced when fat accumulation is renewed during the cold season remains unclear. Therefore, in this study, we examine the effect of environmental temperature on the expression of cortisol synthesis-related enzymes and a glucocorticoid receptor in the subcutaneous fat (blubber) and explore the association between these expressions and fluctuations in circulating cortisol levels in common bottlenose dolphins (Tursiops truncatus). Skin biopsies were obtained seasonally from eight female dolphins, and seasonal differences in the expression of target genes in the blubber were analyzed. Blood samples were collected throughout the year, and cortisol levels were measured. We found that the expressions of cytochrome P450 family 21 subfamily A member 2 (CYP21A2) and nuclear receptor subfamily 3 group C member 1 (NR3C1), a glucocorticoid receptor, were increased in the cold season, and 11 beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) showed a similar trend. Blood cortisol levels increased when the water temperature decreased. These results suggest that the conversion of 17-hydroxyprogesterone to cortisol via 11-deoxycortisol and/or of cortisone to cortisol is enhanced under cold conditions, and the physiological effects of cortisol in subcutaneous adipose tissue may contribute to on-site lipid accumulation and increase the circulating cortisol concentrations. The results obtained in this study highlight the role of cortisol in the regulation of the blubber that has developed to adapt to aquatic life.

Clusters of adipose tissue dysfunction in adults with type 2 diabetes identify those with worse lipidomic profile despite similar glycaemic control.

AIMS: To investigate clusters of adipose tissue dysfunction, that is, with adipose tissue insulin resistance (ADIPO-IR) and large waist circumference (WC), identify a worse lipidomic profile characterised by a high proportion of lipids rich in saturated fatty acids (SFA). MATERIALS AND METHODS: Hierarchical clustering based on WC and ADIPO-IR (calculated as fasting plasma non-esterified fatty acids times fasting plasma insulin, FFA×INS), was performed in 192 adults with overweight/obesity and type 2 diabetes (T2D) treated with metformin (HbA1c = 7.8%). Free fatty acid composition and lipidomic profile were measured by mass spectrometry (GC-MS and LC-MSQTOF). Indexes of fatty acid desaturation (stearoyl-coA desaturase-1 activity, SCD116 = palmitoleic acid/palmitic acid and SCD118 = oleic acid/stearic acid) and of insulin resistance (HOMA-IR) were also calculated. RESULTS: Three clusters were identified: CL1 (ADIPO-IR = 4.9 ± 2.4 and WC = 96±7 cm, mean ± SD), CL2 (ADIPO-IR = 6.5 ± 2.5 and WC = 114 ± 7 cm), and CL3 (ADIPO-IR = 15.0 ± 4.7 and WC = 107 ± 8 cm). Insulin concentrations, ADIPO-IR, and HOMA-IR significantly increased from CL1 to CL3 (all p < 0.001), while fasting glucose concentrations, HbA1c, dietary lipids and caloric intake were similar. Moreover, CL3 showed significantly higher concentrations of monounsaturated free fatty acids, oleic and palmitoleic acids, triglycerides (TAG) rich in saturated FA and associated with de novo lipogenesis (i.e., TAG 46-50), higher SCD116, SCD118, ceramide (d18:0/18:0), and phosphatidylcholine aa(36:5) compared with CL1/CL2 (all p < 0.005). CONCLUSIONS: High ADIPO-IR and large WC identify a worse lipid profile in T2D characterised by complex lipids rich in SFA, likely due to de novo synthesis given higher plasma monounsaturated FFA and increased desaturase activity indexes. REGISTRATION NUMBER TRIAL: ID NCT00700856 https://clinicaltrials.gov.

Discordant gene expression in subcutaneous adipose and skeletal muscle tissues in response to exercise training.

Exercise has different effects on different tissues in the body, the sum of which may determine the response to exercise and the health benefits. In the present study, we aimed to investigate whether physical training regulates transcriptional network communites common to both skeletal muscle (SM) and subcutaneous adipose tissue (SAT). Eight such shared transcriptional communities were found in both tissues. Eighteen young overweight adults voluntarily participated in 7 weeks of combined strength and endurance training (five training sessions per week). Biopsies were taken from SM and SAT before and after training. Five of the network communities were regulated by training in SM but showed no change in SAT. One community involved in insulin- AMPK signaling and glucose utilization was upregulated in SM but downregulated in SAT. This diverging exercise regulation was confirmed in two independent studies and was also associated with BMI and diabetes in an independent cohort. Thus, the current finding is consistent with the differential responses of different tissues and suggests that body composition may influence the observed individual whole-body metabolic response to exercise training and help explain the observed attenuated whole-body insulin sensitivity after exercise training, even if it has significant effects on the exercising muscle.

Wound healing capacity of using mesenchymal stem cell-derived exosomes originated from human adipose tissue and cold atmospheric plasma.

Background: Recently, cold atmospheric plasma (CAP), as well as adipose mesenchymal stem cells derived exosomes (ADMSCs-EX), have been applied separately to wound healing treatment. However, no study has investigated the additive effect on the healing mechanism of these two methods in the same skin lesion treatment model. Aim: We conduct this study to describe the results of using CAP and human ADMSCs-EX on in vitro wound healing. Methods: Exosomes were isolated from donor adipose tissue samples by ultracentrifugation method, characterized by transmission electron microscopy (TEM) and Western blot. Assessment in vitro wound healing on proliferation and migration evaluation experiments on human fibroblasts with culture medium supplemented with 10µg total exosomal proteins/1 mL and irradiated with CAP with an intensity of 30 seconds/cm2. Results: Experimental results to evaluate the ability to stimulate fibroblast migration, showed that cell migration speed in the group supplemented with ADMSCs-EX was equivalent to the group with a combination of CAP and ADMSCs-EX and had the highest rate with 87.8 ± 4.2 % and 84.4 ± 5.3 % while in the control group it was the lowest with 61.9 ± 11.4% (p<0.05). The group supplemented with CAP gave fibroblast proliferation and migration results similar to the control group (p>0.05), showing the safety of CAP with the growth of the cells. Conclusions: Therefore, in animal models, we intend to use a combination of these two therapies by using ADMSCs-EX injection therapy into the dermis at the wound edge to avoid the impact of CAP affecting the cell proliferation.

Assessing Long-Term Volume Retention in Breast Fat Grafting: A Comparative Study of Lipoaspirate Processing Techniques.

INTRODUCTION: Autologous fat grafting is a method of improving aesthetic outcomes after both breast reconstruction and aesthetic surgery through volume enhancement and tissue contouring. Long-lasting effects are linked to greater patient satisfaction and more optimal augmentation results. Harvesting, processing, and injection techniques may all affect the longevity of deformity filling. Our objective is to evaluate the effect of lipoaspirate processing modality on longitudinal volume retention after surgery. METHODS: A prospective, single-institution, randomized control trial placed consented postmastectomy fat grafting patients into 1 of 3 treatment arms (active filtration, low-pressure decantation, and standard decantation) in a 1:1:1 ratio. A preoperative 3-dimensional scan of the upper torso was taken as baseline. At the 3-month postoperative visit, another 3D scan was taken. Audodesk Meshmixer was used to evaluate the volume change. RESULTS: The volume of fat injected during the initial procedure did not differ significantly between the treatment arms (P > 0.05). Both active filtration and low-pressure decantation resulted in higher percentage volume retention than traditional decantation (P < 0.05). Active filtration and low-pressure decantation exhibited comparable degrees of fat maintenance at 3 months (P > 0.05). DISCUSSION: Compared with using traditional decantation as the lipoaspirate purification technique, active filtration and low-pressure decantation may have led to higher levels of cell viability by way of reduced cellular debris and other inflammatory components that may contribute to tissue resorption and necrosis. Further immunohistochemistry studies are needed to examine whether active filtration and low-pressure decantation lead to lipoaspirates with more concentrated viable adipocytes, progenitor cells, and factors for angiogenesis.

Proliferation Patterns of MCF-7 Breast Cancer Cells in Lipoaspirate Conditioned Media.

INTRODUCTION: Autologous fat grafting (AFG) is a common technique used to enhance aesthetic outcomes in postmastectomy breast reconstruction patients. Adipokines are hormones secreted by adipose tissue that play a critical role in regulating metabolic processes and the immune system. However, dysregulated adipokine secretion and signaling can contribute to the development and progression of cancer by promoting angiogenesis, altering the immune response, and inducing the epithelial mesenchymal transition. We aimed to assess how breast cancer cells behave in conditioned media derived from fat grafting lipoaspirates and gain a better understanding of the potential interactions that may occur within the tumor microenvironment. METHODS: Patients who were undergoing AFG as a part of breast reconstruction at NY-Presbyterian/Weill Cornell Medical Center between March 2021 and July 2023 were consented and enrolled in the study. This study was approved by the Weill Cornell Medicine Institutional Review Board (#20-10022850-14). Conditioned media is created using 20% of patient lipoaspirate secretome and 80% starving media. The growth of MCF-7, a human ER/PR+ breast cancer cell line, in conditioned media is assessed using CyQUANT. RESULTS: The breast cancer cells incubated in conditioned media displayed similar growth trends as those in complete media, which is enriched for cell growth (P > 0.05). MCF-7 cell behavior in conditioned media differed significantly from their proliferation patterns when serum starved in 100% starving media (P < 0.05). DISCUSSION: Our results suggest that there may be inherent factors within the lipoaspirate that may promote MCF-7 proliferation. One potential implication is that AFG used for breast reconstruction should be delayed until local-regional disease control has been established. In addition, based on the in vitro proliferation patterns of breast cancer cells in conditioned media, the safety profile of AFG may be enhanced if the procedure is performed after attaining negative margins and the completion breast cancer treatment.

Subcutaneous injection of adipose stromal cell-secretome improves renal function and reduces inflammation in established acute kidney injury.

BACKGROUND: Adipose stromal cells (ASC) are a form of mesenchymal stromal cells that elicit effects primarily via secreted factors, which may have advantages for the treatment of injury or disease. Several previous studies have demonstrated a protective role for MSC/ASC on mitigating acute kidney injury but whether ASC derived factors could hasten recovery from established injury has not been evaluated. METHODS: We generated a concentrated secretome (CS) of human ASC under well-defined conditions and evaluated its ability to improve the recovery of renal function in a preclinical model of acute kidney injury (AKI) in rats. 24 h following bilateral ischemia/reperfusion (I/R), rats were randomized following determination of plasma creatinine into groups receiving vehicle -control or ASC-CS treatment by subcutaneous injection (2 mg protein/kg) and monitored for evaluation of renal function, structure and inflammation. RESULTS: Renal function, assessed by plasma creatinine levels, recovered faster in ASC-CS treated rats vs vehicle. The most prominent difference between the ASC-CS treated vs vehicle was observed in rats with the most severe degree of initial injury (Pcr > 3.0 mg/dl 24 h post I/R), whereas rats with less severe injury (Pcr < 2.9 mg/dl) recovered quickly regardless of treatment. The quicker recovery of ASC-treated rats with severe injury was associated with less tissue damage, inflammation, and lower plasma angiopoietin 2. In vitro, ASC-CS attenuated the activation of the Th17 phenotype in lymphocytes isolated from injured kidneys. CONCLUSIONS: Taken together, these data suggest that ASC-CS represents a potent therapeutic option to improve established AKI.

PPAR-γ regulates the polarization of M2 macrophages to improve the microenvironment for autologous fat grafting.

The unpredictable survival rate of autologous fat grafting (AFG) seriously affects its clinical application. Improving the survival rate of AFG has become an unresolved issue in plastic surgery. Peroxisome proliferator-activated receptor-γ (PPAR-γ) regulates the adipogenic differentiation of adipocytes, but the functional mechanism in AFG remains unclear. In this study, we established an animal model of AFG and demonstrated the superior therapeutic effect of PPAR-γ regulation in the process of AFG. From day 3 after fat grafting, the PPAR-γ agonist rosiglitazone group consistently showed better adipose integrity, fewer oil cysts, and fibrosis. Massive macrophage infiltration was observed after 7 days. At the same time, M2 macrophages begin to appear. At day 14, M2 macrophages gradually became the dominant cell population, which suppressed inflammation and promoted revascularization and fat regeneration. In addition, transcriptome sequencing showed that the differentially expressed genes in the Rosiglitazone group were associated with the pathways of adipose regeneration, differentiation, and angiogenesis; these results provide new ideas for clinical treatment.