Adipose Tissue Transplantation Research Articles

Clinically Relevant and Precisely Printable Live Adipose Tissue-Based Bio-Ink for Volumetric Soft Tissue Reconstruction.

Autologous fat is widely used in soft tissue reconstruction; however, significant volume reduction owing to necrosis and degradation of the transplanted adipose tissue (AT) remains a major challenge. To address this issue, a novel live AT micro-fragment-based bio-ink (ATmf bio-ink) compatible with precision 3D printing, is developed. Live AT micro-fragments of ≈280µm in size are prepared using a custom tissue micronizer and they are incorporated into a fibrinogen/gelatin mixture to create the ATmf bio-ink. AT micro-fragments exhibit high viability and preserve the heterogeneous cell population and extracellular matrix of the native AT. The developed bio-ink enables precise micropatterning and provides an excellent adipo-inductive microenvironment. AT grafts produced by co-printing the bio-ink with polycaprolactone demonstrate a 500% improvement in volume retention and a 300% increase in blood vessel infiltration in vivo compared with conventional microfat grafts. In vivo engraftment of AT grafts is further enhanced by using a stem cell-laden ATmf bio-ink. Last, it is successfully demonstrated that the bio-ink is enabled for the creation of clinically relevant and patient-specific AT grafts for patients undergoing partial mastectomy. This novel ATmf bio-ink for volumetric soft tissue reconstruction offers a pioneering solution for addressing the limitations of existing clinical techniques.

The effect of exogenous mitochondria in enhancing the survival and volume retention of transplanted fat tissue in a nude mice model

BackgroundDespite the pivotal role of fat grafting in plastic, reconstructive, and aesthetic surgery, inconsistent survival rates of transplanted adipose tissue, primarily due to early ischemic and hypoxic insults, remain a significant challenge. The infusion of healthy mitochondria has emerged as a promising intervention to support tissue recovery from ischemic, hypoxic, and other types of damages across various organ systems.ObjectivesThis study aims to evaluate the impact of supplementing human adipose tissue grafts with healthy exogenous mitochondria on their volume and mass retention rates when transplanted into the subcutaneous layers of nude mice. This approach seeks to improve and optimize fat grafting techniques.MethodsHuman adipose tissues were preconditioned with exogenous mitochondria (10 µg/mL), a combination of exogenous mitochondria and the inhibitor Dyngo-4a, Dyngo-4a alone, or PBS, and then transplanted into the subcutaneous tissue of 24 nude mice. Samples were harvested at 1 and 3 months post-transplantation for analysis of mass and volume retention. The structural morphology and integrity of the adipose tissues were assessed using Hematoxylin and Eosin (H&E) staining.ResultsMitochondrial preconditioning significantly enhanced the retention of mass and volume in fat grafts, demonstrating superior structural morphology and integrity compared to the control group.ConclusionsThis study highlights the potential of exogenous mitochondrial augmentation in fat transplantation to significantly improve fat graft survival, thereby optimizing the success of fat grafting procedures.

Autologous Cryopreserved Adipose Tissue Using an Innovative Technique: An In Vitro Biological Characterization

Abstract Background Utilization of autologous adipose tissue transplantation in plastic and orthopedic surgery such as breast reconstruction and intra-articular injection has become an attractive surgical treatment with satisfactory clinical outcomes. Nevertheless, repeated liposuctions necessary to harvest fatty tissue, normally performed with sedation or general anesthesia, may represent a noteworthy concern. Objectives The aim of this study was to demonstrate through an in vitro characterization the validity of the surgical option of cryopreserved autologous adipose tissue harvested in a single shot for repeated graft transfer in breast reconstruction without impairment of cell viability and sterility. Methods Adipose tissue was collected by standard liposuction from patients who needed numerous fat grafting procedures for breast reconstruction. According to an innovative and patented cryopreservation method, autologous adipose tissue was subsequently fractioned in a sterile bag system and frozen at the RER Tissue Bank of the Emilia Romagna Region. Each graft was evaluated for sterility and cell viability immediately after harvesting, and 1, 3, 6, 12, and preliminarily 18 months after cryopreservation and thawing. Results In vitro results showed that after processing, middle-term and long-term cryopreservation, and subsequent thawing, autologous cryopreserved adipose tissue retained absence of bacterial contamination, high cellular viability, and unmodified histomorphological properties, thereby ensuring maintenance of the stromal vascular niche and the filling properties in different multistep surgical procedures. Conclusions In vitro study and sterility assessment showed that autologous cryopreserved adipose tissue grafting is a safe procedure, making it possible to avoid multiple liposuction surgery. No impairment of sterility, cell viability, or morphology was observed over time.

PAQR4 regulates adipocyte function and systemic metabolic health by mediating ceramide levels.

PAQR4 is an orphan receptor in the PAQR family with an unknown function in metabolism. Here, we identify a critical role of PAQR4 in maintaining adipose tissue function and whole-body metabolic health. We demonstrate that expression of Paqr4 specifically in adipocytes, in an inducible and reversible fashion, leads to partial lipodystrophy, hyperglycaemia and hyperinsulinaemia, which is ameliorated by wild-type adipose tissue transplants or leptin treatment. By contrast, deletion of Paqr4 in adipocytes improves healthy adipose remodelling and glucose homoeostasis in diet-induced obesity. Mechanistically, PAQR4 regulates ceramide levels by mediating the stability of ceramide synthases (CERS2 and CERS5) and, thus, their activities. Overactivation of the PQAR4-CERS axis causes ceramide accumulation and impairs adipose tissue function through suppressing adipogenesis and triggering adipocyte de-differentiation. Blocking de novo ceramide biosynthesis rescues PAQR4-induced metabolic defects. Collectively, our findings suggest a critical function of PAQR4 in regulating cellular ceramide homoeostasis and targeting PAQR4 offers an approach for the treatment of metabolic disorders.

M2 Macrophage Polarization and Tissue Remodeling in Autologous Fat Grafting for Diabetic Skin Defects.

Autologous adipose tissue was recognized as a promising therapeutic option for soft tissue defects owing to its regenerative potential and ability to facilitate tissue reconstruction. However, the mechanisms by which autologous fat grafting (AFG) promotes healing remain unclear, hindering its potential applications. This study aimed to investigate the distribution and phenotypic transition of infiltrating macrophages in transplanted adipose tissue, as well as their correlation with diabetic skin defect remodeling. Streptozotocin-induced diabetic rats with full-thickness dorsal skin defects were included in this study. The transplanted adipose tissue at the skin defects was collected and analyzed using flow cytometry to determine macrophage proportion and phenotype. The healing of skin defects was evaluated, and treatment was continued until day 14 as the designated endpoint of healing, followed by histopathologic examinations. Immunostaining with CD31 and lymphatic vessel endothelial receptor-1 was performed on wound tissues to analyze angiogenesis and lymphangiogenesis, respectively. Western blot and quantitative polymerase chain reaction analyses were used to assess the expression of the representative genes involved in the healing process. The results showed early polarization of M2 macrophages in the transplanted adipose tissue, concomitant with the upregulation of growth factors and downregulation of inflammatory factors. In vivo experiments revealed that AFG significantly promoted macrophage infiltration and M2 transformation in diabetic skin defects compared to the control groups, thereby promoting tissue extracellular matrix remodeling and lymphatic and vascular regeneration. However, the beneficial effects of AFG were inhibited by macrophage depletion. This study further demonstrated the potential of AFG for treating diabetic skin defects.

Abstract PO4-27-11: Fat grafting is oncologically safe during implant-based breast reconstruction and mastectomy after radiotherapy for breast cancer or Hodgkin Lymphoma: results of a multicentric study

Abstract Background. Fat grafting during or after mastectomy could promote the regeneration of irradiated tissues, thus improving tissue softness, increasing patient comfort and ameliorating quality of life. However, there are no conclusive data about the oncological safety of fat grafting, especially in terms of risk of tumor recurrences. The most appropriate timing of adipose tissue transplant is also debated, especially in patients with locoregional breast cancer (BC) recurrence undergoing salvage mastectomy and implant-based breast reconstruction after breast conserving surgery and radiotherapy. Methods. We conducted a prospective, multicentric Italian study to investigate the oncological safety of fat grafting between June 2007 and March 2022. One hundred sixty-three patients who had previously received radiotherapy, either as adjuvant treatment after breast conservative surgery (N=154), or as a treatment of Hodgkin Lymphoma (N=9), underwent mastectomy (simple mastectomy, NAC-sparing and skin-sparing mastectomy) and implant-based, two-stage breast reconstruction. Inclusion criteria were: age between 25 and 75 years, absence of concomitant malignancies, grade 2 or 3 of Breast post Radiotherapy Reconstruction with ExpAnder Score Test (B.R.R.E.A.S.T. score) (Tab 1). Patient BMI, hypertension, smoking history, diabetes and having received neoadjuvant chemotherapy were not considered as exclusion criteria. Contextual mastectomy and expander positioning were performed during first stage (stage I), while substitution of the expander with definitive implant occurred during second stage (stage II). Fat grafting could be performed during stage I, between stage I and II surgery, or during stage II. Results. One hundred sixty-nine mastectomy procedures (six bilateral) and first-stage implant-based reconstructions with expander were performed either as prophylactic surgery (N=23) or for the treatment of primary or recurrent BC (N=146). Thirty-four patients had ductal carcinoma in situ, whereas 112 patients had invasive disease, including: 17 patients with Luminal A BC, 67 patients with Luminal B HER2-negative BC, 3 patients with Luminal B HER-2 positive BC, 7 patients with HER-2 positive BC and 18 patients had triple-negative BC. One hundred thirty-six (80.5%) patients received at least one fat grafting. Eighty-six patients (52.8%) have received second-stage definitive implant. With a median time of observation of 25.1 months, we observed four locoregional cancer recurrences (2.4%), one of which in axillary lymph nodes. All tumor recurrences occurred in patients who had received fat grafting. Eight patients (4.9%) developed distant metastases (liver, lung, lymph nodes, and bone metastases); of these, four patients (50%) had received fat grafting. No death events occurred. Conclusion. Fat grafting after radiotherapy of the breast is associated with a low incidence of locoregional tumor recurrences and distant metastases. Although our findings need to be confirmed in larger, multicentric clinical studies, fat grafting is a safe and useful technique that can be proposed for breast reconstruction after irradiation. Table. Breast post Radiotherapy Reconstruction with ExpAnder Score Test, B.R.R.E.A.S.T score. Based on our experience, we thought to include two tissue characteristics (Pinch test ≥ 0.5 cm and presence/absence of skin teleangectasia or severe dyscromia) in a pre-operative, clinically useful, and ready-to-use score to assess soft tissue adequacy as recommended by NCCN guidelines, that we called Breast post Radiotherapy Reconstruction with ExpAnder Score Test (B.R.R.E.A.S.T. score). In our study, two-stage implant-based breast reconstruction and adipose tissue transplant with regenerative intent were performed in patients with Pinch test ≥ 0.5 cm but moderate skin teleangectasia or dyscromia (B.R.R.E.A.S.T. score 2) and in patients with Pinch test ≥ 0.5 cm and absence of skin teleangectasia or severe dyscromia (B.R.R.E.A.S.T. score 3). Patients with skin teleangectasia or dyscromia and Pinch test < 0.5 cm (B.R.R.E.A.S.T. score 1) were not enrolled in our study as they did not undergo alloplastic breast reconstruction but they underwent autologous reconstruction (data not shown). Citation Format: Chiara Listorti, Claudio Vernieri, Francesco Barretta, Chiara Osio, Ilaria Maugeri, Federica Pilotta, Cristina Ferraris, Massimiliano Gennaro, Gabriele Martelli, Marco Visaggio, Giulia Valeria Bianchi, Serena Di Cosimo, Gianfranco Scaperrotta, Maria Carmen De Santis, Daniela Tognali, Antonino Romeo, Matteo Mingozzi, Francesco Marongiu, Annalisa Curcio, Secondo Folli. Fat grafting is oncologically safe during implant-based breast reconstruction and mastectomy after radiotherapy for breast cancer or Hodgkin Lymphoma: results of a multicentric study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-27-11.

Transplantation of Cold-Stimulated Subcutaneous Adipose Tissue Improves Fat Retention and Recipient Metabolism.

Induction of beige fat for grafting is an emerging transplantation strategy. However, safety concerns associated with pharmaceutical interventions limit its wider application. Moreover, because beige fat is a special type of fat with strong metabolic functions, its effect on the metabolism of recipients after grafting has not been explored in the plastic surgery domain. The aim of this study was to explore whether cold-induced inguinal white adipose tissue (iWAT) transplantation has a higher retention rate and beneficial effects on recipient metabolism. C57/BL6 mice were subjected to cold stimulation for 48 hours to induce the browning of iWAT and harvested immediately. Subsequently, each mouse received a transplant of 0.2 mL cold-induced iWAT or normal iWAT. Fat grafts and recipients' iWAT, epididymal adipose tissue, and brown adipose tissue were harvested at 8 weeks after operation. Immunofluorescence staining, real-time polymerase chain reaction, and western blot were used for histological and molecular analysis. Cold-induced iWAT grafting had a higher mean [standard error of the mean] retention rate (67.33% [1.74%] vs 55.83% [2.94%], P < .01) and more satisfactory structural integrity than normal iWAT. Histological changes identified improved adipose tissue homeostasis after cold challenge, including abundant smaller adipocytes, higher levels of adipogenesis, angiogenesis, and proliferation, but lower levels of fibrosis. More importantly, cold-induced iWAT grafting suppressed the inflammation of epididymal adipose tissue caused by conventional fat grafting, and activated the glucose metabolism and thermogenic activity of recipients' adipose tissues. Cold-induced iWAT grafting is an effective nonpharmacological intervention strategy to improve the retention rate and homeostasis of grafts. Furthermore, it improves the adverse effects caused by traditional fat grafting, while also conferring metabolic benefits.

Arachidonic acid inhibit granulosa cell function by affecting metabolic function of liver in brown adipose transplantation rats

BackgroundPolycystic ovary syndrome (PCOS) is a gynecological endocrine disease and could be considered a metabolic disease because it is often accompanied by obesity and insulin resistance. Brown adipose tissue (BAT) transplantation has been shown to be effective in treating PCOS rats.ResultsThe study demonstrated that BAT successfully recovered the reproductive and metabolic phenotype of PCOS rats. The disorder estrous cycle, abnormal hyperglycemia and the expression of liver factors were improved. Differentially expressed metabolites were analyzed, among them, arachidonic acid may play a role in inhibiting cell proliferation, enhancing oxidative stress reaction, promoting estrogen expression, and reducing progesterone level in KGN cells.ConclusionOur findings suggest that BAT transplantation may be a therapeutic strategy for PCOS by changing the expression of some cytokines and metabolites. Differentially expressed metabolites might be crucially important for the pathogenesis of PCOS.

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.

Activated Human Adipose Tissue Transplantation Promotes Sensorimotor Recovery after Acute Spinal Cord Contusion in Rats.

Traumatic spinal cord injuries (SCIs) often result in sensory, motor, and vegetative function loss below the injury site. Although preclinical results have been promising, significant solutions for SCI patients have not been achieved through translating repair strategies to clinical trials. In this study, we investigated the effective potential of mechanically activated lipoaspirated adipose tissue when transplanted into the epicenter of a thoracic spinal contusion. Male Sprague Dawley rats were divided into three experimental groups: SHAM (uninjured and untreated), NaCl (spinal cord contusion with NaCl application), and AF (spinal cord contusion with transplanted activated human fat). Pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) were measured to assess endogenous inflammation levels 14 days after injury. Sensorimotor recovery was monitored weekly for 12 weeks, and gait and electrophysiological analyses were performed at the end of this observational period. The results indicated that AF reduced endogenous inflammation post-SCI and there was a significant improvement in sensorimotor recovery. Moreover, activated adipose tissue also reinstated the segmental sensorimotor loop and the communication between supra- and sub-lesional spinal cord regions. This investigation highlights the efficacy of activated adipose tissue grafting in acute SCI, suggesting it is a promising therapeutic approach for spinal cord repair after traumatic contusion in humans.

Transplantation of beige adipose organoids fabricated using adipose acellular matrix hydrogel improves metabolic dysfunction in high-fat diet-induced obesity and type 2 diabetes mice.

Transplantation of brown adipose tissue (BAT) is a promising approach for treating obesity and metabolic disorders. However, obtaining sufficient amounts of functional BAT or brown adipocytes for transplantation remains a major challenge. In this study, we developed a hydrogel that combining adipose acellular matrix (AAM) and GelMA and HAMA that can be adjusted for stiffness by modulating the duration of light-crosslinking. We used human white adipose tissue-derived microvascular fragments to create beige adipose organoids (BAO) that were encapsulated in either a soft or stiff AAM hydrogel. We found that BAOs cultivated in AAM hydrogels with high stiffness demonstrated increased metabolic activity and upregulation of thermogenesis-related genes. When transplanted into obese and type 2 diabetes mice, the HFD + BAO group showed sustained improvements in metabolic rate, resulting in significant weight loss and decreased blood glucose levels. Furthermore, the mice showed a marked reduction in nonalcoholic liver steatosis, indicating improved liver function. In contrast, transplantation of 2D-cultured beige adipocytes failed to produce these beneficial effects. Our findings demonstrate the feasibility of fabricating beige adipose organoids in vitro and administering them by injection, which may represent a promising therapeutic approach for obesity and diabetes.

Subcutaneous white adipose tissue independently regulates burn-induced hypermetabolism via immune-adipose crosstalk

Severe burns induce a chronic hypermetabolic state that persists well past wound closure, indicating that additional internal mechanisms must be involved. Adipose tissue is suggested to be a central regulator in perpetuating hypermetabolism, although this has not been directly tested. Here, we show that thermogenic adipose tissues are activated in parallel to increases in hypermetabolism independent of cold stress. Using an adipose tissue transplantation model, we discover that burn-derived subcutaneous white adipose tissue alone is sufficient to invoke a hypermetabolic response in a healthy recipient mouse. Concomitantly, transplantation of healthy adipose tissue alleviates metabolic dysfunction in a burn recipient. We further show that the nicotinic acetylcholine receptor signaling pathway may mediate an immune-adipose crosstalk to regulate adipose tissue remodeling post-injury. Targeting this pathway could lead to innovative therapeutic interventions to counteract hypermetabolic pathologies.

Use of brown adipose tissue transplantation and engineering as a thermogenic therapy in obesity and metabolic disease.

The induction of thermogenesis in brown adipose tissue is emerging as an attractive therapy for obesity and metabolic syndrome. However, the long-term efficacy and safety of clinical pharmaceutical agents have yet to be fully characterized. The transplantation of brown adipose tissue represents an alternative approach that might have a therapeutic effect by inducing a long-term increase in energy expenditure. However, limited tissue resources hinder the development of transplantation. Stem cell-based therapy and brown adipose tissue engineering, in addition to transplantation, represent alternative approaches that might resolve this problem. In this article, we discuss recent advances in understanding the mechanisms and applications of brown adipose tissue transplantation in the treatment of obesity and related metabolic disorders. Specifically, the induction of brown adipocytes and the fabrication of engineered brown adipose tissue as novel transplantation resources have long-term effects on ameliorating metabolic defects in rodent models. Additionally, we explore future prospects regarding the development of three-dimensional engineered brown adipose tissue and the associated challenges.

Fat transplant: Amazing growth and regeneration of cells and rebirth with the miracle of fat cells.

During fat transplantation, adipose tissue is removed from the body and injected into different areas under the skin. The goal of this review article is to look into the efficacy and applicability of fat transplantation in regenerative medicine and rejuvenation, including Nanofat, Microfat, and Millifat. As a search strategy and study selection, we searched the PubMed and Medline databases until 2023 using related keywords (e.g., Nanofat, Microfat and Millifat, Regenerative Medicine, and Rejuvenation). Autologous fat transplantation has no risk of an allergic reaction or rejection of the transplant by the individual. Autologous adipose tissue is considered an ideal filler for facial rejuvenation and is suggested as the most biocompatible and non-immunogenic skin filler. Adipose tissue transplant may have semi-permanent to permanent effects. According to recent reports, adipose tissues possess a high percentage of mature stem cells. The effect of regenerating adipose tissue and its intrinsic cells can be described as an obvious process. Variations in the sizes of adipose tissues can result in different results depending on the surgical site. Based on topographic assessment, graft fats are assigned depending on the anatomical locations and the size such as Millifat (2-2.5 mm), Microfat (1 mm), and Nanofat (500 μm or less). Some characteristics of fat tissue increase its effectiveness, such as increasing stem cells, growth factors, cytokines, and compounds effective in repair, regeneration, and rejuvenation.

Brown adipose tissue transplantation improves skin fibrosis in localized scleroderma.

Adipose tissue transplantation shows great therapeutic potential in reversing localized scleroderma-associated skin fibrosis. Brown adipose tissue (BAT) can specifically secrete various cytokines against fibrosis, but its therapeutic potential in improving skin fibrosis has not yet been demonstrated. In this study, we have demonstrated the superior therapeutic efficacy of BAT transplantation for sclerotic skin by transplanting two distinct types of adipose tissue. In comparison to the white adipose tissue (WAT) group, mice treated with BAT transplantation exhibited a significant reduction in dermal thickness. BAT transplantation effectively reverses skin sclerosis through mechanisms involving inflammation reduction, promotion of angiogenesis, inhibition of myofibroblast accumulation, and collagen deposition. This therapeutic effect can be attributed to its unique paracrine effects. Furthermore, transcriptome sequencing (RNA-Seq) revealed upregulation of pathways associated with lipogenesis and fatty acid metabolism in BAT while downregulating pathways are related to transforming growth factor β(TGF-β), epithelial-mesenchymal transition (EMT), and inflammatory response. These findings suggest that BAT transplantation holds great promise as a novel approach for localized scleroderma treatment.

Physical Expansion Preconditioning Promotes Host-Derived Adipocyte Dedifferentiation and Migration into Fat Grafts in a Murine Model.

The unstable recipient conditions after fat grafting remain an obstacle for tissue volumization. The interaction between fat grafts and recipient sites is not fully understood. The authors hypothesize that recipient-derived adipocytes undergo dedifferentiation and migrate into fat grafts in tissue regeneration. To observe the participation from recipient fat pad, the authors established a recipient adipocyte-tracing model where 0.2 mL of inguinal fat from 10 8-week-old C57BL/6 mice was grafted to 10 tamoxifen-treated AdipoqCre;mT/mG mice. Next, to evaluate the impact of physical force on recipient fat and fat graft, a murine internal expansion model was established by implanting a 1-mL internal expander on the inguinal fat pad of the lineage tracing mice that received fat graft from C57BL/6 mice. Transplanted adipose tissue was collected and analyzed by immunostaining of green fluorescent protein (GFP), tdTomato, perilipin, and CD31. In the observing model, immunostaining revealed that both GFP+ and tdTomato + cells from the recipient fat pad presented in fat grafts. Among the GFP + cells, most of them were perilipin + adipocytes and other perilipin - cells co-expressed octamer-binding transcription factor 4, indicating dedifferentiated adipocytes. In the internal expansion model, internal expansion increased GFP + cells in fat graft. Both octamer-binding transcription factor 4-positive/GFP + (0.23 ± 0.01 versus 0.12 ± 0.04) and perilipin + /GFP + (0.17 ± 0.02 versus 0.06 ± 0.01) cells were increased in the expanded group, compared with control. Host-derived adipocytes participate in fat graft regeneration through migration and dedifferentiation, which could be enhanced by internal expansion to increase fat graft retention rate. Further study using a larger animal model is needed, because this is a murine study. Surgeons are encouraged to use physical expansion preconditioning of the recipient site. Subsequent and multiple fat grafting into the fat layer is encouraged to obtain satisfactory soft-tissue volumization.

Adipose transplantation improves olfactory function and neurogenesis via PKCα-involved lipid metabolism in Seipin Knockout mice

BackgroundLipodystrophy-associated metabolic disorders caused by Seipin deficiency lead to not only severe lipodystrophy but also neurological disorders. However, the underlying mechanism of Seipin deficiency-induced neuropathy is not well elucidated, and the possible restorative strategy needs to be explored.MethodsIn the present study, we used Seipin knockout (KO) mice, combined with transcriptome analysis, mass spectrometry imaging, neurobehavior test, and cellular and molecular assay to investigate the systemic lipid metabolic abnormalities in lipodystrophic mice model and their effects on adult neurogenesis in the subventricular zone (SVZ) and olfactory function. After subcutaneous adipose tissue (AT) transplantation, metabolic and neurological function was measured in Seipin KO mice to clarify whether restoring lipid metabolic homeostasis would improve neurobehavior.ResultsIt was found that Seipin KO mice presented the ectopic accumulation of lipids in the lateral ventricle, accompanied by decreased neurogenesis in adult SVZ, diminished new neuron formation in the olfactory bulb, and impaired olfactory-related memory. Transcriptome analysis showed that the differentially expressed genes (DEGs) in SVZ of adult Seipin KO mice were significantly enriched in lipid metabolism. Mass spectrometry imaging showed that the levels of glycerophospholipid and diglyceride (DG) were significantly increased. Furthermore, we found that AT transplantation rescued the abnormality of peripheral metabolism in Seipin KO mice and ameliorated the ectopic lipid accumulation, concomitant with restoration of the SVZ neurogenesis and olfactory function. Mechanistically, PKCα expression was up-regulated in SVZ tissues of Seipin KO mice, which may be a potential mediator between lipid dysregulation and neurological disorder. DG analogue (Dic8) can up-regulate PKCα and inhibit the proliferation and differentiation of neural stem cells (NSCs) in vitro, while PKCα inhibitor can block this effect.ConclusionThis study demonstrates that Seipin deficiency can lead to systemic lipid disorder with concomitant SVZ neurogenesis and impaired olfactory memory. However, AT restores lipid homeostasis and neurogenesis. PKCα is a key mediator mediating Seipin KO-induced abnormal lipid metabolism and impaired neurogenesis in the SVZ, and inhibition of PKCα can restore the impaired neurogenesis. This work reveals the underlying mechanism of Seipin deficiency-induced neurological dysfunction and provides new ideas for the treatment of neurological dysfunction caused by metabolic disorders.

From scarcity to solutions: Therapeutic strategies to restore adipose tissue functionality in rare disorders of lipodystrophy.

Lipodystrophy is a rare disorder characterised by abnormal or deficient adipose tissue formation and distribution. It poses significant challenges to affected individuals, including the development of severe metabolic complications like diabetes and fatty liver disease. These conditions are often chronic, debilitating and life-threatening, with limited treatment options and a lack of specialised expertise. This review aims to raise awareness of lipodystrophy disorders and highlights therapeutic strategies to restore adipose tissue functionality. Extensive research has been conducted, including both historical and recent advances. We have examined and summarised the literature to provide an overview of potential strategies to restore adipose tissue functionality and treat/reverse metabolic complications in lipodystrophy disorders. A wealth of basic and clinical research has investigated various therapeutic approaches for lipodystrophy. These include ground-breaking methods such as adipose tissue transplantation, innovative leptin replacement therapy, targeted inhibition of lipolysis and cutting-edge gene and cell therapies. Each approach shows great potential in addressing the complex challenges posed by lipodystrophy. Lipodystrophy disorders require urgent attention and innovative treatments. Through rigorous basic and clinical research, several promising therapeutic strategies have emerged that could restore adipose tissue functionality and reverse the severe metabolic complications associated with this condition. However, further research and collaboration between academics, clinicians, patient advocacy groups and pharmaceutical companies will be crucial in transforming these scientific breakthroughs into effective and viable treatment options for individuals and families affected by lipodystrophy. Fostering such interdisciplinary partnerships could pave the way for a brighter future for those battling this debilitating disorder.

Study on the Application of Concentrated Growth Factor Combined With Adipose Transplantation in Repairing Depressed Deformity of Soft Tissue in the Face.

Autologous fat is a rich source of adipose tissue that is safe for transplantation. Decreasing the long-term absorption rate is key to improve the survival of transplanted adipose tissue. The aim of this study was to assess the effect of concentrated growth factor (CGF) on the survival of transplanted adipose tissue for repair of facial depression malformations. Coleman adipose granules (CAGs) were prepared from venous blood. In the animal experiment, the ears of 30 healthy male New Zealand white rabbits were randomly allocated to 1 of 4 groups: CGF + CAG (CGF group), platelet-rich fibrin (PRF) + CAG (PRF group), CAG alone (CAG group), and adipose granule transplantation group (control group). Postoperative survival of the transplanted adipose tissue was assessed, the survival and absorption rates of adipose were calculated, and immunohistochemical analysis of specimens was conducted by staining with hematoxylin and eosin and Oil Red O. Of 43 outpatients, 22 received simple adipose transplantation and 21 received autologous CGF combined with adipose transplantation. The adipose absorption rate, complication rate, and cosmetic improvement of the 2 groups were compared. More adipocytes that are normal were observed in the CGF group, with fewer vacuoles and more uniform distribution of adipose tissue. Survival of the adipose tissue was superior in the CGF and PRF groups. Meanwhile, vascular density and long-term stability were better in the CGF group than the PRF group. In terms of clinical efficacy, the uniformity and survival rate of the adipose tissue were relatively improved in the CGF group compared with the simple adipose particle transplantation group, with less early liquefaction. Concentrated growth factor stabilized and improved the survival of transplanted adipose tissue for filling of facial depression malformations.

Ferroptosis in Autologous Fat Transplantation: A New Hypothesis.

Autologous adipose tissue transplantation is widely used for cosmetic and reconstruction of various areas in the body, often to repair soft tissue volume loss or contoured deformation. However, the application of fat transplantation is limited by unstable and unpredictable volume retention rates. At present, promoting adipose tissue survival and inhibiting its death is the key to improve the effect of autologous fat transplantation. In this paper, we propose a hypothesis that ferroptosis exists in fat transplantation. The bases of this hypothesis include the following: (1) the association between ferroptosis and other programmed cell death; (2) the association between ferroptosis and ischemia-reperfusion injury; and (3) the use of ferroptosis inhibitors in the field of fat transplantation.