Transplantation of purified autologous fat: a 3-year follow-up is disappointing.

The idea of autologous fat microtransplants has recently resurfaced because of interest by the press. Past experiments have shown that small amounts of fat may be transplanted with an expected survival rate between 10 and 50 percent without ectodermis. A great fund of knowledge exists showing that skin grafts will survive quite dependably if their thickness is up to about 0.0020 inch. For the first week or so, they live by diffusion and inosculation, and then neovascularization enables them to continue viability. I have developed a technique whereby fat is harvested through a blunt cannula with minimal vacuum to prevent explosion of the cellular fat globules. Fibrin and cellular debris are removed, and the fat globules are separated from the free fat, blood, and other constituents of the aspirate. Individual, free-floating 1- to 3-mm adipose fragments are then suspended in nutrient solution and injected through an 18-gauge needle. Multiple radial pathways, with each fat segment being separated from the other by host tissue, maximizes the host-prosthesis interface and the possibility for exchange of nutrients. I have attempted this procedure in more than 100 patients with widely varying results. In acne pits of the face, no significant improvement could be noted 6 weeks after injection. For the first few weeks, a near-perfect result was obtained, but none of these transplants in scarred areas of this kind have been of benefit. Injection of 10 to 50 cc in other areas has resulted in some cells (perhaps 10 percent) surviving over 2 years.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gynecomastia: suction lipectomy as a contemporary solution

Suction lipectomy is adapted for the correction of gynecomastia. Previous attempts using suction lipectomy for gynecomastia still required the use of sharp dissection for removal of the glandular breast tissue as well as excision of redundant skin. With this new technique, gynecomastia is corrected solely with the use of suction lipectomy. The technique is successful if the gynecomastia is due to excess fat or parenchymal hypertrophy. A 7-mm cannula is inserted first, to remove the adipose tissue. Then a 2.4-mm cannula is used to remove the glandular and ductal tissue. The 7-mm cannula is then reinserted to remove subareolar parenchyma and to make final contour adjustments. The surrounding subcutaneous tissue is easily undermined to avoid a saucer deformity and to allow for skin contraction. Patients return to full activities in 48 hours. A compressive garment is worn for 4 to 6 weeks. The results of 10 patients are discussed.     

Compensation for an increase in body fat caused by donor transplants into mice

Rodents tend to compensate for experimental obesity in which both adipocyte size and number are increased. In contrast, it was recently reported that Siberian hamsters do not compensate for dorsal subcutaneous transplants of fat, which increase body fat without changing the size of adipocytes. In the first experiment described here we tested whether mice changed the size of their endogenous fat stores 2 or 5 wk after donor fat was added as subcutaneous transplants. Each epididymal fat pad from donor mice was cut in half and placed ventrally in recipient mice, increasing body fat by approximately 10%. After 2 wk, there was no effect of the transplants on the size of endogenous fat depots or the size of adipocytes in epididymal fat depots. There was a substantial decrease in mass and adipocyte size in transplanted fat. Five weeks after surgery the endogenous epididymal and retroperitoneal fat depots of recipient mice were significantly decreased, serum leptin was reduced, and the size of adipocytes in endogenous epididymal fat was significantly reduced, although cell number had not changed. The size of transplanted cells was the same as at 2 wk. In a second experiment, epididymal fat was placed as either dorsal or ventral subcutaneous fat transplants. Five weeks after surgery the endogenous fat depots were decreased in all recipient mice but none of the differences reached statistical significance. These results suggest that mice have mechanisms to maintain total body fat mass that respond to an increase in the number of fat cells present.     

Buttock augmentation: case studies of fat injection monitored by magnetic resonance imaging

This article examines the injection of megavolumes of autologous fat cells as a means of buttock augmentation in 162 patients over a 7-year period. The author documents the use of magnetic resonance imaging in six patients to visualize the intramuscular location, integration, and duration of the injected fat. With the patient under epidural or general anesthesia, fat cells were harvested with a 5-mm blunt cannula and then stored in an empty sterile intravenous bag or bottle trap. Decantation was the only process used to separate the fat cells from the saline and serosanguineous components. Up to 1260 cc of fat cells were been injected into each buttock, the largest amount of fat grafting ever reported. Clinical assessment estimated a 20 percent loss of augmentation effect during the first 4 months. Patients were generally pleased with the final shape and volume of the buttock contour. In follow-up evaluation, magnetic resonance imaging supported the clinical indicators that the injection of large quantities of fat cells appears to be a safe and effective method for buttock enhancement. This process has inherent advantages; nevertheless, further research is required to clarify our understanding of the predictability and longevity of this technique.     

Subcutaneous pseudobursa secondary to suction and surgery

Suction lipectomy has been used throughout the regions of the body to remove vast amounts of subcutaneous fat. The blunt technique allows for a multiplicity of small (4 to 6 mm) channels to be created and the fat removed by suction with little disturbance of the overlying skin, the supporting septa, vessels, or nerves. Abdominolipectomy has been successfully performed for decades, in which large amounts of skin and subcutaneous fat are removed by sharp dissection. The undermining involved in an adbominolipectomy extending from the xiphoid to pubis and laterally to the level of the iliac crest and then supplemented by the suction technique has led to the formation, in some cases, of chronic seromas not relieved by multiple aspirations. Healing and contractions of these seromas causes a deformity of the overlying skin, because it is puckered and drawn upon itself. This results in the formation of a subcutaneous pseudobursa lined by collagen sheets but no epithelial cells. We present 9 patients who have demonstrated this phenomenon. We suggest that in the largest resections, safety is best served by waiting a period of at least 6 weeks between suction and subsequent resection.     

Adipose stromal/stem cells assist fat transplantation reducing necrosis and increasing graft performance

Autologous fat transfer (AFT) is a procedure for adipose tissue (AT) repair after trauma, burns, post-tumor resections and lipodystrophies still negatively impacted by the lack of graft persistence. The reasons behind this poor outcome are unclear and seem to involve damages in either harvested/transplanted mature adipocytes or on their mesenchymal progenitors, namely adipose stromal/stem cells (ASC), and due to post-transplant AT apoptosis and involution. A rabbit subcutaneous AT regeneration model was here developed to first evaluate graft quality at different times after implant focusing on related parameters, such as necrosis and vasculogenesis. Standard AFT was compared with a strategy where purified autologous ASC, combined with hyaluronic acid (HA), assisted AFT. Five million of autologous ex vivo isolated CD29+, CD90+, CD49e+ ASC, loaded into HA, enriched 1 ml of AT generating an early significant protective effect in reducing AFT necrosis and increasing vasculogenesis with a preservation of transplanted AT architecture. This beneficial impact of ASC assisted AFT was then confirmed at three months with a robust lipopreservation and no signs of cellular transformation. By a novel ASC assisted AFT approach we ensure a reduction in early cell death favoring an enduring graft performance possibly for a more stable benefit in patients.     

Development of an Arterio‐venous Difference Method to Study the Metabolic Physiology of the Femoral Adipose Tissue Depot

Gluteofemoral adipose tissue (AT) has interesting positive associations with metabolic health, yet little is known of its metabolic physiology. Here, we describe a technique for cannulation of a vein draining the femoral fat depot. Using ultrasound guidance, a cannula was introduced into a superficial branch of the great saphenous vein. We also obtained arterialized blood and, for comparison, blood representing drainage from forearm muscle and from subcutaneous abdominal AT. We measured appropriate biomarkers of skeletal muscle (creatinine) and AT (nonesterified fatty acids (NEFAs), glycerol, leptin) drainage. Blood obtained in this way from the saphenous vein did not show creatinine release (creatinine concentration 100.5 ± 0.4%, mean ± s.e.m., of that in arterialized blood), whereas creatinine concentrations in blood draining forearm muscle averaged 121 ± 1% of those in arterialized blood. Fatty acid release from the tissue drained was suppressed after feeding and increased during β‐adrenergic stimulation. We also demonstrated leptin secretion. These findings suggest that blood so obtained is representative of AT drainage with little apparent contribution of skeletal muscle. We believe this technique will facilitate physiological studies of a lower‐body fat depot in humans.     

Why change a good thing? Revisiting the fleur-de-lis reconstruction of the breast

Although the latissimus flap is known for its simplicity and reliability, use of the fleur-de-lis pattern was plagued by undesirable T-shaped donor sites and small breast volumes in thin patients. We report a modified technique for optimal shaping of the standard latissimus with the successful application of a modified fleur-de-lis pattern. Because a "wet" tumescent infiltration was utilized and large amounts of subcutaneous fat were harvested, these changes permitted application to a wide variety of patients, with generous breast volumes reducing the size of the implant placed and resulting in excellent donor-site scars.This is a retrospective cohort study of 53 delayed or immediate reconstructions performed consecutively by the principal author (M.E.A.) on 48 patients at a university-based, urban hospital. Each case was analyzed between April of 1995 and February of 1999, with a follow-up from 2.5 to 44 months. All patients underwent injection of tumescent solution into the subcutaneous plane and harvest of large amounts of subcutaneous fat with the neurologically intact latissimus muscle. The last 25 reconstructions utilized the modified fleur-de-lis skin pattern, an inferiorly based vertical limb and replacement of skin deficiency in both axes.Of 11 perioperatively irradiated patients, none required skin grafting, whereas 6 percent of all native mastectomy flaps were grafted. There was one instance of minor distal tip flap necrosis in a nonirradiated patient. No implants became infected or were extruded. Donor sites were without wound complications and unveiled a 16 percent overall seroma rate.Through selective addition of harvested tissue, this modified technique, particularly the fleur-de-lis pattern, permits improved volume and projection in the inferior pole. The T-shaped donor-site closure is not only acceptable, but is also desirable, with reduced wound tension and minimization of dog-ear formation. With a relative paucity of complications, this conceptually ideal modification is technically simple and aesthetically comparable to our transverse rectus abdominis muscle flap results.     

Evaluation of a modified surgical technique to correct urine pooling in cows

Various surgical techniques to correct urovagina in cows describe creating a mucosal extension from the urethral orifice to the labia; however, a fistula often forms in the mucosal extension. The objective of the present study was to determine if the incidence of fistula formation could be decreased by covering transposed submucosal tissue on the dorsal aspect of the urethral extension with a mucosal graft. Cows in both the control group (19) and the experimental group (19) received a modified McKinnon technique of urethral extension; cows in the experimental group also had a sheet of mucosa, obtained from the dorsal aspect of the vestibule, grafted to submucosa exposed during creation of the urethral extension. During histological examination of the biopsy of the graft and its recipient site (harvested 1 week after surgery), neither inosculation nor revascularization of the graft was evident in any sample. Fourteen of 19 (74%) cows in the control group and 10 of 19 (53%) cows in the experimental group developed a fistula in the extension (P=0.18). We concluded that application of a mucosal graft to the subcutaneous tissue exposed to the vestibule using the McKinnon technique of creating a urethral extension was of little or no benefit in preventing the formation of a fistula in the extension. Furthermore, during evaluation of the extensions, digital palpation alone was often insufficient for detection of a fistula.     

Root formation in ectopically transplanted teeth of the frog, Rana pipiens I. Tooth morphogenesis.

In order to determine the intrinsic (genetic) and extrinsic (functional) parts of the naturally ankylosed tooth, a qualitative study of the development and fate of tooth buds transplanted individually or within the premaxilla was carried out. These teeth were transplanted as autografts during crown formation. They were placed in either the anterior chamber of the eye or in a dorsal subcutaneous site. Most of the 163 transplants survived and were examined at intervals from 0 to 180 days by gross, histologic and microradiographic methods. Tooth buds transplanted with or without the premaxilla were capable of growth to normal size and shape. Lack of underlying bone with which to ankylose and lack of normal oral environment and function did not prevent formation of a normal-sized root area. The root area was composed of dentin and covered by a solid, undisrupted Hertwig's epithelial root sheath which appeared to mold the root. Calcified tissue formed on the outside surface of dentin only when the root sheath was accidentally torn during transplantation.     

Analysis of the effects of deep mechanical massage in the porcine model.

Deep mechanical massage has been advocated as an alternative or adjunctive therapy for the contouring of subcutaneous fat and as a treatment for cellulite. We evaluated the effects of deep mechanical massage using two pig models. Yucatan pigs were divided into three groups (n = 4). One side of each body received 4, 10, or 20 treatments and the other side served as a control. Full-thickness tissue sections, including the underlying muscle, were harvested from identical treated and untreated regions. Examination of these regionally matched samples revealed an accumulation of dense, longitudinal collagen bands in the middle dermal and deep subdermal regions, which progressively increased with the number of treatments. Distortion and disruption of adipocytes was noted. In Yorkshire pigs, force-transducing balloon catheters were surgically placed between the deep subcutaneous tissue and muscle fascia. Catheters were inserted into two regions with different skin and subcutaneous tissue characteristics, the midflank and the hip. Standardized maneuvers were performed at suction settings 3, 5, 7, and 9 to record baseline tissue forces. Each maneuver carried a unique force signature. The measurement of tissue forces was repeated on the opposite side after 10 standardized treatment sessions. Analysis showed a significant reduction of measured forces at the midflank after the treatments. The actual force measured with each particular maneuver varied between different operators but not with different suction settings, suggesting that the technique of administering the treatments is the primary factor in creating the force within the tissue. This leads to the conclusion that deep mechanical massage is highly dependent on the individual operator of the device.     

Location, location, location..

Intra-abdominal fat is an established risk factor for the metabolic syndrome. In this issue of Cell Metabolism, Tran et al. (2008) test the cell-autonomous and location-related properties of transplanted intra-abdominal and subcutaneous fat depots. While subcutaneous fat seems to confer metabolic benefits, species differences in adipose biology justify caution in interpreting the results.     

Age-associated adipose tissue inflammation promotes monocyte chemotaxis and enhances atherosclerosis

Although aging enhances atherosclerosis, we do not know if this occurs via alterations in circulating immune cells, lipid metabolism, vasculature, or adipose tissue. Here, we examined whether aging exerts a direct pro-atherogenic effect on adipose tissue in mice. After demonstrating that aging augmented the inflammatory profile of visceral but not subcutaneous adipose tissue, we transplanted visceral fat from young or aged mice onto the right carotid artery of Ldlr^−/− recipients. Aged fat transplants not only increased atherosclerotic plaque size with increased macrophage numbers in the adjacent carotid artery, but also in distal vascular territories, indicating that aging of the adipose tissue enhances atherosclerosis via secreted factors. By depleting macrophages from the visceral fat, we identified that adipose tissue macrophages are major contributors of the secreted factors. To identify these inflammatory factors, we found that aged fat transplants secreted increased levels of the inflammatory mediators TNFα, CXCL2, and CCL2, which synergized to promote monocyte chemotaxis. Importantly, the combined blockade of these inflammatory mediators impeded the ability of aged fat transplants to enhance atherosclerosis. In conclusion, our study reveals that aging enhances atherosclerosis via increased inflammation of visceral fat. Our study suggests that future therapies targeting the visceral fat may reduce atherosclerosis disease burden in the expanding older population.     

Autologous fat graft in nipple reconstruction

Reconstruction of the nipple is the penultimate step in breast reconstruction after mastectomy. A number of reconstructive techniques have been described for nipple reconstruction including skin grafts, composite grafts, and various local flaps. The authors' preferred reconstructive technique is the local C-V or modified star flap. This flap produces an excellent reconstruction, but it is dependent on underlying subcutaneous fat to provide bulk to the reconstructed nipple. In most instances, the subcutaneous tissue is adequate. However, under certain circumstances, the subcutaneous fat may be insufficient to produce a nipple of adequate projection. Two cases of bilateral nipple reconstruction after soft-tissue expansion and implant placement and subsequent nipple reconstruction with local flaps provided inadequate nipple projection. These instances, as well as a retrospective review of reconstructed nipples after mound restoration using a variety of techniques, led the authors to conclude that a more predictable alternative to sustain nipple projection was necessary. The authors identified two broad categories of breast reconstruction patients in whom this new technique would be beneficial. In the first category of patients, breast mounds are reconstructed with tissue expansion and implant insertion, and in the second category, breast mounds are reconstructed by any technique in which the nipple reconstruction subsequently flattens. This article describes the indications, techniques, and experience in 13 patients treated over a 10-month period with fat grafting for nipple reconstruction.     

Gender differences in tumor necrosis factor alpha and leptin secretion from subcutaneous and visceral fat tissue

Tumor necrosis factor alpha (TNFalpha) and leptin concentrations were determined in the abdominal subcutaneous and visceral (omental) adipose tissue of patients undergoing elective open-abdominal surgery and compared with their body mass index. The concentration of leptin did not differ significantly between women and men, being high in subcutaneous fat tissue and low in visceral fat tissue. TNFalpha concentration in subcutaneous fat tissue was approximately the same in both genders, but it was significantly lower in visceral fat tissue of women and unchanged in visceral fat tissue of men. A significant correlation between BMI and leptin was found in the two fat tissue compartments of both genders, but the correlation between BMI and TNFalpha was found only in subcutaneous fat tissue of women.     

Fetal intestinal transplants in syngeneic rats: a developmental model of intestinal immunity

We conducted a longitudinal study of the development of lymphoid tissue in fetal small intestine transplanted to a subcutaneous site in adult syngeneic Fischer strain rats. Fetal jejunoileal segments obtained between 18 and 21 days of gestation were transplanted to a dorsal subcutaneous site on syngeneic adult rats. Three weeks later, intestinal segments greater than 2.5 cm in length were found in 70% of recipients. Each week for 6 wk post-transplantation, a full-thickness biopsy was obtained for histologic and immunohistologic examination. At the time of transplantation, fetal rat intestine did not display Peyer's patches, intraepithelial lymphocytes, lymphoid follicles, or IgA-containing plasma cells. These lymphoid structures reached adult levels by 4 wk after transplantation, and the sequence of development of the lymphoid structures in the transplants appeared to match the postnatal development of normal small intestine. After immunizing the in situ intestine or the transplanted fetal intestine with cholera toxin, the number of cells producing specific antibodies to the immunogen increased significantly in intestinal transplants and in situ intestine. In contrast, few if any cells synthesizing antibodies to cholera toxin developed in the transplants after i.p. immunization. This study suggests that fetal intestinal transplants behave as part of the mucosal immune system. This model may provide useful approaches to studying the development of mucosal immunity.     

Higher Free Fatty Acid Uptake in Visceral Than in Abdominal Subcutaneous Fat Tissue in Men

Visceral adipose tissue has been shown to have high lipolytic activity. The aim of this study was to examine whether free fatty acid (FFA) uptake into visceral adipose tissue is enhanced compared to abdominal subcutaneous tissue in vivo. Abdominal adipose tissue FFA uptake was measured using positron emission tomography (PET) and [¹⁸F]‐labeled 6‐thia‐hepta‐decanoic acid ([¹⁸F]FTHA) and fat masses using magnetic resonance imaging (MRI) in 18 healthy young adult males. We found that FFA uptake was 30% higher in visceral compared to subcutaneous adipose tissue (0.0025 ± 0.0018 vs. 0.0020 ± 0.0016 µmol/g/min, P = 0.005). Visceral and subcutaneous adipose tissue FFA uptakes were strongly associated with each other (P < 0.001). When tissue FFA uptake per gram of fat was multiplied by the total tissue mass, total FFA uptake was almost 1.5 times higher in abdominal subcutaneous than in visceral adipose tissue. In conclusion, we observed enhanced FFA uptake in visceral compared to abdominal subcutaneous adipose tissue and, simultaneously, these metabolic rates were strongly associated with each other. The higher total tissue FFA uptake in subcutaneous than in visceral adipose tissue indicates that although visceral fat is active in extracting FFA, its overall contribution to systemic metabolism is limited in healthy lean males. Our results indicate that subcutaneous, rather than visceral fat storage plays a more direct role in systemic FFA availability. The recognized relationship between abdominal visceral fat mass and metabolic complications may be explained by direct effects of visceral fat on the liver.     

Depot-Specific Changes in Fat Metabolism with Aging in a Type 2 Diabetic Animal Model

Visceral fat accretion is a hallmark of aging and is associated with aging-induced metabolic dysfunction. PPARγ agonist was reported to improve insulin sensitivity by redistributing fat from visceral fat to subcutaneous fat. The purpose of this study was to investigate the underlying mechanisms by which aging affects adipose tissue remodeling in a type 2 diabetic animal model and through which PPARγ activation modulates aging-related fat tissue distribution. At the ages of 21, 31 and 43 weeks, OLETF rats as an animal model of type 2 diabetes were evaluated for aging-related effects on adipose tissue metabolism in subcutaneous and visceral fat depots. During aging, the ratio of visceral fat weight to subcutaneous fat weight (V/S ratio) increased. Aging significantly increased the mRNA expression of genes involved in lipogenesis such as lipoprotein lipase, fatty acid binding protein aP2, lipin 1, and diacylglycerol acyltransferase 1, which were more prominent in visceral fat than subcutaneous fat. The mRNA expression of adipose triglyceride lipase, which is involved in basal lipolysis and fatty acid recycling, was also increased, more in visceral fat compared to subcutaneous fat during aging. The mRNA levels of the genes associated with lipid oxidation were increased, whereas the mRNA levels of genes associated with energy expenditure showed no significant change during aging. PPARγ agonist treatment in OLETF rats resulted in fat redistribution with a decreasing V/S ratio and improved glucose intolerance. The genes involved in lipogenesis decreased in visceral fat of the PPARγ agonist-treated rats. During aging, fat distribution was changed by stimulating lipid uptake and esterification in visceral fat rather than subcutaneous fat, and by altering the lipid oxidation.     

Role of DHEA-S on body fat distribution: gender- and depot-specific stimulation of adipose tissue lipolysis

The objective of this work was to study the possible impact of DHEA-S on body fat distribution and the specific action of the hormone on lipolysis from visceral and subcutaneous human adipose tissue. First, a clinical evaluation was performed in 84 obese patients (29 men, 55 women), measuring serum DHEA-S, computed tomography (CT) anthropometric parameters of abdominal fat distribution. In a second experiment, subcutaneous and visceral adipose tissue samples were obtained from 20 obese patients (10 men, 10 women) and cultured in vitro under stimulation with DHEA-S to further assess a possible effect of this hormone on adipose tissue lipolysis. Serum DHEA-S was inversely and specifically associated with visceral fat area (VA) as assessed by CT in men and with waist-to-hip ratio in women. In vitro, DHEA-S increased lipolysis in women's subcutaneous adipose tissue at 2 h, while in men, the effect was evident in visceral tissue and after 24 h of treatment. In conclusion, DHEA-S contributes to gender-related differences in body fat distribution probably by a differential lipolytic action. We have demonstrated for the first time in vitro that DHEA-S stimulates lipolysis preferably in subcutaneous fat in women and in visceral fat in men.