Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 63
Filter
1.
Cell Metab ; 36(6): 1287-1301.e7, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38838641

ABSTRACT

Adipocytes in dermis are considered to be important participants in skin repair and regeneration, but the role of subcutaneous white adipose tissue (sWAT) in skin repair is poorly understood. Here, we revealed the dynamic changes of sWAT during wound healing process. Lineage-tracing mouse studies revealed that sWAT would enter into the large wound bed and participate in the formation of granulation tissue. Moreover, sWAT undergoes beiging after skin injury. Inhibition of sWAT beiging by genetically silencing PRDM16, a key regulator to beiging, hindered wound healing process. The transcriptomics results suggested that beige adipocytes in sWAT abundantly express neuregulin 4 (NRG4), which regulated macrophage polarization and the function of myofibroblasts. In diabetic wounds, the beiging of sWAT was significantly suppressed. Thus, adipocytes from sWAT regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes.


Subject(s)
Adipose Tissue, White , Skin , Wound Healing , Animals , Adipose Tissue, White/metabolism , Mice , Skin/metabolism , Skin/pathology , Mice, Inbred C57BL , Subcutaneous Fat/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Neuregulins/metabolism , Neuregulins/genetics , Male , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Adipose Tissue, Brown/metabolism , Adipocytes, Beige/metabolism , Macrophages/metabolism , Humans , Myofibroblasts/metabolism
2.
Front Endocrinol (Lausanne) ; 15: 1365156, 2024.
Article in English | MEDLINE | ID: mdl-38686209

ABSTRACT

Obesity is a chronic disease that affects the energy balance of the whole body. In addition to increasing fat mass, tissue fibrosis occurred in white adipose tissue in obese condition. Fibrosis is the over-activation of fibroblasts leading to excessive accumulation of extracellular matrix, which could be caused by various factors, including the status of adipocytes. The morphology of adipocytes responds rapidly and dynamically to nutrient fluctuations. Adaptive hypertrophy of normal adipocytes protects peripheral organs from damage from lipotoxicity. However, the biological behavior of hypertrophic adipocytes in chronic obesity is abnormally altered. Adipocytes lead to fibrotic remodeling of the extracellular matrix by inducing unresolved chronic inflammation, persistent hypoxia, and increasing myofibroblast numbers. Moreover, adipocyte-induced fibrosis not only restricts the flexible expansion and contraction of adipose tissue but also initiates the development of various diseases through cellular autonomic and paracrine effects. Regarding anti-fibrotic therapy, dysregulated intracellular signaling and epigenetic changes represent potential candidate targets. Thus, modulation of adipocytes may provide potential therapeutic avenues for reversing pathological fibrosis in adipose tissue and achieving the anti-obesity purpose.


Subject(s)
Adipocytes , Fibrosis , Obesity , Humans , Obesity/pathology , Obesity/metabolism , Adipocytes/pathology , Adipocytes/metabolism , Animals , Adipose Tissue/pathology , Adipose Tissue/metabolism
3.
Aesthetic Plast Surg ; 48(13): 2536-2544, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38538770

ABSTRACT

Type IV collagen is a major component of the extracellular matrix in adipose tissue. It is secreted during the lipogenic differentiation of mesenchymal stem cells, but its direct impact and mechanism on the differentiation of adipose-derived stem cells (ASCs) into lipids are unclear. In this study, ASCs were obtained from human liposuction samples and cultured. Lipogenic induction of ASCs was achieved using lipogenic induction medium. Immunofluorescence analysis revealed differential expression of type IV collagen during the early and late stages of adipogenic induction, displaying a distinct morphological encapsulation of ASCs. Silencing of type IV collagen using siRNA resulted in a significant decrease in adipogenic capacity, as indicated by reduced lipid droplet formation and downregulation of adipogenic-related gene transcription. Conversely, supplementation of the culture medium with synthetic type IV collagen demonstrated enhanced adipogenic induction efficiency, accompanied by upregulation of YAP/TAZ protein expression and its downstream target gene transcription. Furthermore, inhibition of the YAP/TAZ pathway using the inhibitor Blebbistatin attenuated the functionality of type IV collagen, leading to decreased lipid droplet formation and downregulation of adipocyte maturation-related gene expression. These findings highlight the crucial role of type IV collagen in promoting adipogenic differentiation of ASCs and suggest its involvement in the YAP/TAZ-mediated Hippo pathway.No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Subject(s)
Adipogenesis , Cell Differentiation , Collagen Type IV , Humans , Adipogenesis/physiology , Adipogenesis/genetics , Collagen Type IV/genetics , Collagen Type IV/metabolism , Cells, Cultured , Adipose Tissue/cytology , Adipocytes , Female , Stem Cells , Adult
4.
Aesthetic Plast Surg ; 48(11): 2147-2154, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38551708

ABSTRACT

BACKGROUND: Facial aging involves ptosis, adipose atrophy, and skeletal resorption. Depletion of adipose tissue primarily affects the deep facial fat compartment, leading to facial depression or ptosis, accompanied by atrophy of the superficial compartment. Restoring volume in the deep fat compartment is crucial for facial rejuvenation, while enhancing its supportive properties is also important. The superficial fat compartment contains small-sized adipocytes, and autologous fat grafting is a popular approach. However, variability in fat retention, homogeneity, and processing methods can impact outcomes, necessitating careful selection of a suitable fat processing material for precise facial fat grafting. METHOD: A retrospective study was conducted on 50 patients who underwent facial augmentation using combined transplantation of high-density fat (HDF) and condensed low-density fat (CLDF) and 25 patients who underwent conventional Coleman fat grafting. Coleman fat was harvested by standard technique and the adipose tissue was divided into HDF and CLDF fractions through centrifugation. Subsequently, the low-density fat fraction was subjected to a process involving physical disruption followed by additional centrifugation to obtain CLDF. The CLDF fraction was consequently injected into the pre-SMAS subcutaneous layer of the superficial fat compartments. Patient satisfaction was evaluated using a typical Likert scale. Photographs were taken and imageological examinations were performed before and after treatment. RESULT: The CLDF+HDF grafting group demonstrated a significantly shorter duration of swelling (6.0 ± 1.2 to 12.6 ± 3.3 days) and higher level of patient satisfaction when compared to the Coleman fat group. No serious complications were observed among all the patients who received the injections. CONCLUSION: The use of this new treatment approach allows for precise fat transplantation in facial regions. The use of high-concentration fat filling for deep facial layers and CLDF filling for superficial layers is a safe and effective treatment plan for facial rejuvenation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Subject(s)
Adipose Tissue , Rejuvenation , Humans , Rejuvenation/physiology , Retrospective Studies , Female , Middle Aged , Adipose Tissue/transplantation , Adult , Male , Treatment Outcome , Transplantation, Autologous/methods , Patient Satisfaction , Cosmetic Techniques , Skin Aging , Cohort Studies , Face/surgery , Esthetics
5.
J Cell Physiol ; 239(4): e31191, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38219044

ABSTRACT

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.


Subject(s)
Adipose Tissue, Brown , Diabetes Mellitus, Type 2 , Diet, High-Fat , Organoids , Animals , Humans , Mice , Adipose Tissue, Brown/transplantation , Adipose Tissue, White/metabolism , Diabetes Mellitus, Type 2/etiology , Diabetes Mellitus, Type 2/surgery , Diet, High-Fat/adverse effects , Hydrogels/pharmacology , Obesity/metabolism , Thermogenesis , Mice, Nude , Male , Organoids/transplantation
6.
Plast Reconstr Surg ; 153(3): 549e-554e, 2024 03 01.
Article in English | MEDLINE | ID: mdl-36988657

ABSTRACT

BACKGROUND: Autologous fat grafting is frequently used for volume augmentation and tissue regeneration. The uniform physical and biological characteristics of fat grafts, however, limit their optimal effects in various situations. Subjecting fat tissue to different mechanical processes results in adipose-derived products with distinct biological components and physical features. The present study describes a novel facial fat-grafting strategy, adipose component transplantation (ACT), that yields different adipose products that can be applied to specific injection sites. METHODS: All patients who underwent ACT were evaluated retrospectively. Fat tissue samples were fractionated into high-density fat, adipose matrix complex, stromal vascular fraction gel, and adipose collagen fragment, as described. Each of these fractions was processed and injected into indicated recipient sites. Additional SVF gel was cryopreserved and, if necessary, injected during the following 3 months. Patients were followed up after 1, 2, 3, and 6 months, and annually thereafter. RESULTS: From March of 2020 to September of 2021, 78 patients underwent whole face fat grafting using the ACT strategy. All operations and secondary injections of cryopreserved SVF gel were uneventful. There were no major complications, and final aesthetic results were satisfactory in 91% of patients. CONCLUSIONS: The ACT strategy allows specific adipose products to be applied to specific injection sites, as warranted. Adipose matrix complex is indicated for sufficient rigid support, high-density fat when large volumes are required, SVF gel for precise injection and cryopreservation, and ACF as mesotherapy for skin rejuvenation. The ACT strategy optimizes the biological functions and physical features of different adipose-derived products. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Subject(s)
Adipose Tissue , Rejuvenation , Humans , Retrospective Studies , Adipose Tissue/transplantation , Wound Healing , Face/surgery
7.
Front Cell Infect Microbiol ; 13: 1265872, 2023.
Article in English | MEDLINE | ID: mdl-38145043

ABSTRACT

In this report, we present a case study of a rare human bacterium, Corynebacterium bovis, which caused an infection in a patient who had undergone autologous fat-based breast augmentation using cryopreserved fat. This infection occurred during a secondary fat grafting procedure. To identify the bacteria causing the infection, we used high-throughput DNA sequencing technology since this bacterium is seldomly reported in human infections. The patient was successfully treated with intravenous imipenem. We also discuss potential factors that may have contributed to this unusual bacterial infection and propose that DNA sequencing can be a useful tool in cases where standard culture techniques fail to identify the causative agent. Additionally, we highlight the importance of further research on the cryopreservation of fat. In summary, this case highlights the possibility of rare bacterial infections occurring after fat grafting procedures and emphasizes the importance of identifying the causative agent through advanced techniques such as DNA sequencing. Further research is needed to improve our understanding of the risks associated with cryopreservation of fat and to identify ways to prevent these types of infections in the future.


Subject(s)
Adipose Tissue , Mammaplasty , Humans , Transplantation, Autologous/adverse effects , Transplantation, Autologous/methods , Mammaplasty/methods , Retrospective Studies
8.
FASEB J ; 37(12): e23315, 2023 12.
Article in English | MEDLINE | ID: mdl-37983652

ABSTRACT

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 ß(TGF-ß), epithelial-mesenchymal transition (EMT), and inflammatory response. These findings suggest that BAT transplantation holds great promise as a novel approach for localized scleroderma treatment.


Subject(s)
Adipose Tissue, Brown , Scleroderma, Localized , Mice , Animals , Adipose Tissue, Brown/metabolism , Scleroderma, Localized/therapy , Scleroderma, Localized/metabolism , Scleroderma, Localized/pathology , Adipose Tissue , Adipose Tissue, White/metabolism , Skin/pathology , Fibrosis
9.
Plast Reconstr Surg ; 2023 Sep 19.
Article in English | MEDLINE | ID: mdl-37734113

ABSTRACT

BACKGROUND: The unstable recipient conditions after fat grafting remains an obstacle for tissue volumization. The interaction between fat grafts and recipient sites is not fully understood. We hypothesize that recipient-derived adipocytes undergo dedifferentiation and migrate into fat grafts in tissue regeneration. METHODS: To observe the participation from recipient fat pad, we established a recipient adipocyte-tracing model where 0.2 ml inguinal fat from ten 8-week-old C57BL/6 mice was grafted to ten tamoxifen-treated AdipoqCre;mT/mG mice. Next, to evaluate the impact of physical force on recipient fat and fat graft, murine internal expansion model was established by implanting a 1 ml internal expander upon 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 GFP, tdTomato, perilipin, CD31. RESULTS: In the observing model, immunostaining revealed that both GFP+ and tdTomato+ cells from recipient fat pad presented in fat grafts. Among the GFP+ cells, most of them were perilipin+ adipocytes and other perilipin- cells co-expressed OCT4, indicating dedifferentiated adipocytes. In the internal expansion model, internal expansion increased GFP+ cells in fat graft. Both OCT4+/GFP+ (0.23 ± 0.01 vs. 0.12 ± 0.04) and perilipin+/GFP+ (0.17 ± 0.02 vs. 0.06 ± 0.01) cells were increased in the expanded group, compared with control. CONCLUSIONS: 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 larger animal model is needed, since this is a murine study.

10.
Stem Cell Res Ther ; 14(1): 207, 2023 08 21.
Article in English | MEDLINE | ID: mdl-37605289

ABSTRACT

Stem cell therapy is the most promising treatment option for regenerative medicine. Therapeutic effect of different stem cells has been verified in various disease model. Dedifferentiated fat (DFAT) cells, derived from mature adipocytes, are induced pluripotent stem cells. Compared with ASCs and other stem cells, the DFAT cells have unique advantageous characteristics in their abundant sources, high homogeneity, easily harvest and low immunogenicity. The DFAT cells have shown great potential in tissue engineering and regenerative medicine for the treatment of clinical problems such as cardiac and kidney diseases, autoimmune disease, soft and hard tissue defect. In this review, we summarize the current understanding of DFAT cell properties and focus on the relevant practical applications of DFAT cells in cell therapy in recent years.


Subject(s)
Induced Pluripotent Stem Cells , Regenerative Medicine , Tissue Engineering , Cell- and Tissue-Based Therapy , Adipocytes
11.
J Cosmet Dermatol ; 22(12): 3387-3394, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37409535

ABSTRACT

BACKGROUND: The complications of large-volume fat grafting (LVFG) for breast augmentation remain unpredictable and include palpable breast nodules, oil cysts, and calcifications. AIMS: This study was aimed to provide an optimal treatment option for breast nodules after LVFG and evaluate their pathological characteristics. PATIENTS/METHODS: We effectively performed complete resection of breast nodules in 29 patients after LVFG using a minimal skin incision with the vacuum-assisted breast biopsy (VABB) system under ultrasound guidance. And we further carried on histologic examination of excised nodules and evaluated their pathological characteristics. RESULTS: The breast nodules were excised thoroughly with cosmetic effect satisfactorily. Interestingly, subsequent histologic examination showed that type I and VI collagens were strongly expressed in the fibrotic area and type IV collagen were positively expressed around the blood vessel. Furthermore, we found that the type VI collagen+ area appeared around mac2+ macrophages and α-SMA+ myofibroblasts. CONCLUSIONS: The VABB system may be the optimal treatment option for breast nodules after LVFG. And type VI collagens may serve as a biomarker of grafted adipose tissue fibrosis. The relationship between macrophages, fibroblasts, and collagen formation may be therapeutic targets for regulating fibrosis.


Subject(s)
Breast , Mammaplasty , Humans , Breast/diagnostic imaging , Breast/surgery , Breast/pathology , Mammaplasty/adverse effects , Adipose Tissue/transplantation , Biopsy, Needle , Fibrosis , Retrospective Studies
12.
Stem Cells ; 41(9): 837-849, 2023 09 15.
Article in English | MEDLINE | ID: mdl-37338056

ABSTRACT

Mesenchymal stem cells (MSCs) are commonly used as a source for cellular therapy owing to their strong immunosuppressive and regenerative effects. However, MSCs undergo extensive apoptosis within a short period after transplantation. During apoptosis, MSCs generate several apoptotic extracellular vesicles (MSCs-ApoEVs). MSCs-ApoEVs are rich in miRNomes, metabolites, and proteomes. They are critical intercellular communication mediators that can exert different regulatory effects on recipient cells. MSCs-ApoEVs have been shown to promote regeneration in the skin, hair, bone, muscle, and vascular system, etc. This review describes the production, release, isolation, and functionality of ApoEVs in detail. Furthermore, we summarize the existing mechanisms of MSCs-ApoEVs used for tissue regeneration and evaluate the possible strategies for their clinical application.


Subject(s)
Extracellular Vesicles , Mesenchymal Stem Cells , Wound Healing , Mesenchymal Stem Cells/metabolism , Cell- and Tissue-Based Therapy , Apoptosis
13.
Plast Reconstr Surg ; 2023 May 31.
Article in English | MEDLINE | ID: mdl-37285020

ABSTRACT

BACKGROUND: Fat grafting has an unsatisfactory retention rate for breast reconstruction due to poor recipient conditions. The contribution of the recipient site to fat grafts is unknown. In this study, we hypothesize that tissue expansion could improve fat graft retention by preconditioning the recipient fat fad. METHODS: Over-expansion was achieved using 10 ml cylindrical soft-tissue expanders implanted beneath the left inguinal fat flaps of 16 Sprague-Dawley rats (weighing 250-300 g), whose contralateral parts were implanted with a silicone sheet as control. After 7-days expansion, the implants were removed and both inguinal fat flaps received 1 ml of fat grafts from 8 donor rats. Fluorescent dye-labeled mesenchymal stromal cells (MSCs) were injected into rats and tracked in vivo by fluorescence imaging. Transplanted adipose tissue was harvested at 4 and 10 weeks (n = 8 per time point). RESULTS: After 7-days expansion, OCT4+ (p = 0.0002) and Ki67+ (p = 0.0004) positive area were increased with up-regulated expression of CXCL12 in recipient adipose flaps. An increasing number of DiI-positive MSCs were observed in the expanded fat pad. At 10 weeks after fat grafting, retention rate, measured using the Archimedes principle, was much higher in the expanded group than that in the non-expanded group (0.3019 ± 0.0680 vs. 0.1066 ± 0.0402, p = 0.0005). Histologic and transcriptional analyses revealed that angiogenesis was enhanced, and macrophage infiltration was decreased in the expanded group. CONCLUSIONS: Internal expansion preconditioning increased circulating stem cells into recipient fat pad and contributed to improved fat graft retention.

15.
Aesthetic Plast Surg ; 47(1): 387-396, 2023 02.
Article in English | MEDLINE | ID: mdl-36350407

ABSTRACT

BACKGROUND: Although autologous fat grafting is a useful adjunct for breast reconstruction, its indications remain limited as large-volume fat grafting results in high absorption and complication rates. Low-density fat includes small numbers of viable cells and considerable oil, resulting in nodules and oil cysts. This study evaluated the volumization effect and complications with combined fat grafting of condense low-density fat and high-density fat. METHODS: This retrospective, single-center study included 25 patients who underwent combined grafting of condensed low-density fat and high-density fat (CLDF + HDF) and 20 patients who underwent conventional Coleman fat grafting for breast reconstruction from December 2017 to January 2022. Retention rates and complications were evaluated by magnetic resonance imaging and ultrasound rates. Patient satisfaction was evaluated using a typical Likert scale. Photographs were taken and imageological examinations were performed before and after treatment. OUTCOMES: Graft retention rate was higher in patients who underwent CLDF + HDF than Coleman fat grafting for breast reconstruction (38.40 ± 4.41% vs. 31.43 ± 5.43%, p <0.05). One patient in the CLDF + HDF grafting group, compared with twelve in the Coleman fat grafting group, developed oil cysts exceeding 1 cm. Patient satisfaction rate was higher in the CLDF + HDF grafting group. CONCLUSIONS: Mechanical processes can concentrate the cellular content of LDF and remove oil, condensing LDF to the level of HDF. Combined grafting of CLDF optimized by mechanical processing and HDF is effective for breast reconstruction, with a higher retention rate and a lower incidence of complications than conventional Coleman fat grafting. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Subject(s)
Cysts , Mammaplasty , Humans , Retrospective Studies , Adipose Tissue/transplantation , Treatment Outcome , Mammaplasty/methods , Cysts/etiology , Mechanical Phenomena
16.
Stem Cell Res Ther ; 13(1): 493, 2022 10 04.
Article in English | MEDLINE | ID: mdl-36195925

ABSTRACT

BACKGROUND: Postmastectomy radiotherapy is considered to be a necessary treatment in the therapy of breast cancer, while it will cause soft tissue damage and complications, which are closely related to the success rate and effectiveness of breast reconstruction. After radiotherapy, cutaneous tissue becomes thin and brittle, and its compliance decreases. Component fat grafting and adipose-derived stem cell therapy are considered to have great potential in treating radiation damage and improving skin compliance after radiotherapy. MAIN BODY: In this paper, the basic types and pathological mechanisms of skin and soft tissue damage to breast skin caused by radiation therapy are described. The 2015-2021 studies related to stem cell therapy in PubMed were also reviewed. Studies suggest that adipose-derived stem cells exert their biological effects mainly through cargoes carried in extracellular vesicles and soluble secreted factors. Compared to traditional fat graft breast reconstruction, ADSC therapy amplifies the effects of stem cells in it. In order to obtain a more purposeful therapeutic effect, proper stem cell pretreatment may achieve more ideal and safe results. CONCLUSION: Recent research works about ADSCs and other MSCs mainly focus on curative effects in the acute phase of radiation injury, and there is little research about treatment of chronic phase complications. The efficacy of stem cell therapy on alleviating skin fibrosis and its underlying mechanism require further research.


Subject(s)
Breast Neoplasms , Mammaplasty , Soft Tissue Injuries , Adipose Tissue/pathology , Breast Neoplasms/pathology , Breast Neoplasms/radiotherapy , Female , Humans , Mammaplasty/methods , Mastectomy , Soft Tissue Injuries/metabolism , Soft Tissue Injuries/surgery , Stem Cells/metabolism
17.
Stem Cell Res Ther ; 13(1): 499, 2022 10 09.
Article in English | MEDLINE | ID: mdl-36210466

ABSTRACT

BACKGROUND: Localized scleroderma causes cosmetic disfigurement, joint contractures, and other functional impairment, but no currently available medications can reverse the resulting skin lesions. Fat grafting is beneficial for reversing skin fibrosis; however, the mechanism by which adipose tissue transplantation contributes to lesion improvement has not been fully clarified. The purpose of our study was to verify the therapeutic effect of fat grafts in reversing skin fibrosis. METHODS: Inguinal fat pads from AdipoqCreER+;mT/mG mice, which were treated with tamoxifen, were transplanted to the skin lesion in bleomycin-treated wild-type C57 mice. Tdtomato transgenic mice-derived adipocytes, adipose-derived stem cells (ASCs), dedifferentiated adipocytes (DAs) were embedded in matrigel and transplanted beneath the skin lesion of bleomycin-treated wild-type C57 mice. A transwell co-culture system was used to verify the effect of ASCs, adipocytes or DAs on scleroderma fibroblasts or monocytes. RESULTS: Adipocytes from the fat grafts could undergo dedifferentiation and redifferentiation for dermal adipose tissue re-accumulation within the skin lesion. Moreover, compared with ASCs and adipocytes, DAs show greater potency of inducing adipogenesis. ASCs and DAs showed comparable effect on inducing angiogenesis and suppressing macrophage infiltration in fibrotic skin. Co-culture assay showed that DAs and ASCs were able to reduce fibrosis-related genes in human scleroderma fibroblasts and drive M2 macrophage polarization. CONCLUSION: Our results indicated that adipocytes would transform into a more functional and dedifferentiated state and reverse dermal fibrosis, by promoting dermal adipose tissue regeneration, improving angiogenesis, suppressing macrophage-mediated inflammation and myofibroblast accumulation.


Subject(s)
Adipocytes , Skin Diseases , Adipose Tissue , Animals , Bleomycin , Fibrosis , Humans , Mice , Mice, Transgenic , Skin Diseases/pathology , Tamoxifen
18.
Front Bioeng Biotechnol ; 10: 905194, 2022.
Article in English | MEDLINE | ID: mdl-36046675

ABSTRACT

Excess and dysfunctional adipose tissue plays an important role in metabolic diseases, including obesity, atherosclerosis and type 2 diabetes mellitus. In mammals, adipose tissue is categorized into two types: white and brown. Adult brown tissue is mainly composed of beige adipocytes, which dispose of stored energy as heat and have become increasingly popular as a therapeutic target for obesity. However, there is still a paucity of cell models that allow transdifferentiation of mature white adipocytes into beige adipocytes, as seen in vivo. Here, we describe a novel, ceiling culture-based model of human mature white adipocytes, which transdifferentiate into beige adipocytes under the mechanical force and hypoxia of ceiling culture. We also show that the use of rosiglitazone and rapamycin can modulate transdifferentiation, up and down regulating expression of beige adipocyte-specific genes, respectively. Rosiglitazone additionally facilitated the upregulation of fatty acid lipolysis and oxidation genes. Finally, these beige adipocytes derived from dedifferentiated adipocytes exhibited a progenitor-specific phenotype, with higher expression of mature adipocyte-specific genes than adipocyte-derived stem cells. Overall, we report a novel approach to conveniently cultivate beige adipocytes from white adipocytes in vitro, suitable for mechanistic studies of adipose biology and development of cell and drug therapies in the future.

20.
FASEB J ; 36(9): e22510, 2022 09.
Article in English | MEDLINE | ID: mdl-36004579

ABSTRACT

Fat grafting is one of the most commonly applied procedure for soft-tissue repair. However, it remains unclear whether the type of adipose tissue would have any effects on fat graft survival. The present study aimed to determine fates of fat grafting of three different types of fat tissue. In this study, mice were randomly divided into three groups, white adipose tissue (WAT) group, beige adipose tissue (beige AT) group and brown adipose tissue (BAT) group. Before transplantation, donor mice were injected with rosiglitazone or phosphate-buffered saline (PBS). The WAT and BAT were obtained from PBS-treated mice while beige AT was obtained from the rosiglitazone-treated mice. Three types of fat tissue (150 mg each) were transplanted in three groups, respectively, and harvested at 2, 4 or 12 weeks. The BAT and beige AT contained smaller adipocytes and expressed higher level of uncoupling protein-1 gene. The retention rate of the transplanted fat was significantly higher for beige than for white fat, but was significantly lower for brown than for white fat. Transplanted brown fat was characterized by upregulated inflammation and high endoplasmic reticulum stress. By contrast, fat grafts in beige AT group showed the best adipogenic capacity, moderate inflammation level and superior angiongenesis. In vitro, under hypoxic condition, fewer apoptotic cells were found in beige adipocyte group than that in brown and white adipocyte group. Conditioned medium from brown adipocytes induced M1 polarization of RAW 264.7 macrophages while that from beige adipocytes effectively promoted M2 polarization. Therefore, we suggest that beige AT provides a new potential choice for fat grafting because of low inflammation and superior survival but BAT might not be ideal for fat grafting due to its poor survival.


Subject(s)
Adipose Tissue, Beige , Adipose Tissue, Brown , Adipose Tissue, White , Animals , Inflammation , Mice , Rosiglitazone/pharmacology , Thermogenesis/genetics
SELECTION OF CITATIONS
SEARCH DETAIL