RESUMO
Cell therapy for adrenocortical insufficiency can potentially provide steroid replacement in response to physiological stimuli. Previously, we reported that adipose tissue-derived stromal cells (ADSCs) are transformed into steroid-producing cells by overexpression of nuclear receptor subfamily 5 group A member 1 (NR5A1). The steroidogenic cells are characterized by the production of both adrenal and gonadal steroids. Cytotherapy for adrenocortical insufficiency requires cells with more adrenocortical characteristics. Considering the highly developed vascular network within the adrenal cortex, all adrenocortical cells are adjacent to and interact with vascular endothelial cells (VECs). In this study, NR5A1-induced steroidogenic cells derived from mouse ADSCs (NR5A1-ADSCs) were co-cultured with mouse VECs. Testosterone secretion in NR5A1-ADSCs was not altered; however, corticosterone secretion significantly increased while levels of steroidogenic enzymes significantly increased in the corticosterone synthesis pathway. Co-culture with lymphatic endothelial cells (LECs) or ADSCs, or transwell culture with NR5A1-ADSCs and VECs did not alter corticosterone production. VECs expressed higher levels of collagen and laminin than LECs. Culture in type-IV collagen and laminin-coated dishes increased corticosterone secretion in NR5A1-ADSCs. These results suggest that VECs may characterize ADSC-derived steroidogenic cells into a more corticosterone-producing phenotype, and VECs may be useful for generating adrenal steroidogenic cells from stem cells.
Assuntos
Tecido Adiposo , Técnicas de Cocultura , Corticosterona , Células Endoteliais , Células-Tronco Mesenquimais , Animais , Corticosterona/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Células Endoteliais/metabolismo , Células Endoteliais/citologia , Camundongos , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Fator Esteroidogênico 1/metabolismo , Fator Esteroidogênico 1/genética , Células Cultivadas , Diferenciação Celular , Testosterona/metabolismo , Testosterona/biossínteseRESUMO
BACKGROUND: The aim of this study was to evaluate the adverse effects of allogeneic mesenchymal stem cells (MSCs) transplanted via intravenous infusion in dogs and examine their safety. We performed a retrospective analysis of various clinical assessments, including physical examination, blood tests, and radiographs, and monitored the formation of neoplasms during a 6-month follow-up period in 40 client-owned dogs that received intravenous infusion of adipose tissue-derived MSCs (AT-MSCs) for the treatment of various underlying diseases between 2012 and 2018. RESULTS: No significant adverse effects of MSC therapy were detected by clinical assessment, blood tests, or radiographic examination in the 6-month follow-up period after the first MSC treatment. Additionally no new neoplasms were observed during this period. CONCLUSIONS: To our knowledge, this study is the first to evaluate the safety aspects (≥ 6 months) associated with intravenous allogeneic AT-MSC infusion. These results suggest that allogenic AT-MSC infusion could be a useful and relatively safe therapeutic approach in canines.
Assuntos
Doenças do Cão , Transplante de Células-Tronco Mesenquimais , Animais , Cães , Transplante de Células-Tronco Mesenquimais/veterinária , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Feminino , Masculino , Estudos Retrospectivos , Doenças do Cão/terapia , Células-Tronco Mesenquimais , Transplante Homólogo/veterinária , Injeções Intravenosas/veterinária , Tecido Adiposo/citologiaRESUMO
Rhein, a component derived from rhubarb, has been proven to possess anti-inflammatory properties. Here, we show that rhein mitigates obesity by promoting adipose tissue thermogenesis in diet-induced obese mice. We construct a macrophage-adipocyte co-culture system and demonstrate that rhein promotes adipocyte thermogenesis through inhibiting NLRP3 inflammasome activation in macrophages. Moreover, clues from acetylome analysis identify SIRT2 as a potential drug target of rhein. We further verify that rhein directly interacts with SIRT2 and inhibits NLRP3 inflammasome activation in a SIRT2-dependent way. Myeloid knockdown of SIRT2 abrogates adipose tissue thermogenesis and metabolic benefits in obese mice induced by rhein. Together, our findings elucidate that rhein inhibits NLRP3 inflammasome activation in macrophages by regulating SIRT2, and thus promotes white adipose tissue thermogenesis during obesity. These findings uncover the molecular mechanism underlying the anti-inflammatory and anti-obesity effects of rhein, and suggest that rhein may become a potential drug for treating obesity.
Assuntos
Antraquinonas , Macrófagos , Obesidade , Sirtuína 2 , Termogênese , Animais , Masculino , Camundongos , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/efeitos dos fármacos , Antraquinonas/farmacologia , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Sirtuína 2/metabolismo , Sirtuína 2/genética , Termogênese/efeitos dos fármacosRESUMO
This study was to determine whether extracellular vesicles (EVs) derived from insulin-producing cells (IPCs) can modulate naïve mesenchymal stromal cells (MSCs) to become insulin-secreting. MSCs were isolated from human adipose tissue. The cells were then differentiated to generate IPCs by achemical-based induction protocol. EVs were retrieved from the conditioned media of undifferentiated (naïve) MSCs (uneducated EVs) and from that of MSC-derived IPCs (educated EVs) by sequential ultracentrifugation. The obtained EVs were co-cultured with naïve MSCs.The cocultured cells were evaluated by immunofluorescence, flow cytometry, C-peptide nanogold silver-enhanced immunostaining, relative gene expression and their response to a glucose challenge.Immunostaining for naïve MSCs cocultured with educated EVs was positive for insulin, C-peptide, and GAD65. By flow cytometry, the median percentages of insulin-andC-peptide-positive cells were 16.1% and 14.2% respectively. C-peptide nanogoldimmunostaining providedevidence for the intrinsic synthesis of C-peptide. These cells released increasing amounts of insulin and C-peptide in response to increasing glucose concentrations. Gene expression of relevant pancreatic endocrine genes, except for insulin, was modest. In contrast, the results of naïve MSCs co-cultured with uneducated exosomes were negative for insulin, C-peptide, and GAD65. These findings suggest that this approach may overcome the limitations of cell therapy.
Assuntos
Diferenciação Celular , Técnicas de Cocultura , Vesículas Extracelulares , Células Secretoras de Insulina , Insulina , Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Humanos , Vesículas Extracelulares/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/citologia , Peptídeo C/metabolismo , Células Cultivadas , Glucose/metabolismo , Tecido Adiposo/citologia , Tecido Adiposo/metabolismoRESUMO
Obesity-related chronic low-grade inflammation plays a central role in the development of insulin resistance. Macrophages are key players in adipose tissue homeostasis, and their phenotypic shift from the anti-inflammatory or alternatively activated (M2) form to the pro-inflammatory, classically activated (M1) form is a hallmark of insulin resistance. However, adipose tissue macrophages (ATMs) have been identified as a distinct subpopulation of macrophages in several recent studies. These ATMs, described as metabolically activated macrophages (MMe), differ from M1 and are primarily found in the adipose tissue of obese individuals. In our study, we developed an in vitro model of MMe macrophages to establish a simple and reproducible system to understand their characteristics and role in the pathophysiology of insulin resistance. We examined their characteristics such as inflammatory patterns, surface markers, and metabolic features, and compared them with M1 and M2 macrophages. We found that a cell line-based in vitro model effectively mirrors the characteristics of ATMs, highlighting distinct inflammatory phenotypes, metabolism, surface markers, altered lysosomal activity, and ER stress akin to macrophages in vivo. This model captures the subtle distinctions between MMe and M1, and can be effectively used to study several features of macrophage-adipose interactions of therapeutic importance.
Assuntos
Tecido Adiposo , Inflamação , Resistência à Insulina , Macrófagos , Obesidade , Macrófagos/metabolismo , Tecido Adiposo/metabolismo , Humanos , Obesidade/metabolismo , Obesidade/patologia , Inflamação/patologia , Inflamação/metabolismo , Ativação de Macrófagos , Animais , Estresse do Retículo Endoplasmático , CamundongosRESUMO
Feline mesenchymal stem cells (fMSCs) are well known for their robust differentiation capabilities and are commonly used in studying immune-related diseases in cats. Despite their importance, the susceptibility of fMSCs to viral infections remains uncertain. This study aimed to assess the susceptibility of feline adipose-derived mesenchymal stem cells (fAD-MSCs) and feline umbilical cord-derived mesenchymal stem cells (fUC-MSCs) to common feline viruses, including feline coronavirus (FCoV), feline herpesvirus type 1 (FHV-1), and feline panleukopenia virus (FPV). The results demonstrated that both FCoV and FHV-1 were able to infect both types of cells, while FPV did not exhibit cytopathic effects on fUC-MSCs. Furthermore, all three viruses were successfully isolated from fAD-MSCs. These findings suggest that certain feline viruses can replicate in fMSCs, indicating potential limitations in using fMSCs for treating viral diseases caused by these specific viruses. This study has important clinical implications for veterinarians, particularly in the management of viral diseases.
Assuntos
Coronavirus Felino , Células-Tronco Mesenquimais , Animais , Gatos , Células-Tronco Mesenquimais/virologia , Células-Tronco Mesenquimais/citologia , Coronavirus Felino/fisiologia , Vírus da Panleucopenia Felina , Células Cultivadas , Varicellovirus/fisiologia , Replicação Viral , Diferenciação Celular , Tecido Adiposo/citologia , Doenças do Gato/virologiaRESUMO
Pulmonary fibrosis is a progressive disease caused by interstitial inflammation. Treatments are extremely scarce; therapeutic drugs and transplantation therapies are not widely available due to cost and a lack of donors, respectively. Recently, there has been a high interest in regenerative medicine and exponential advancements in stem cell-based therapies have occurred. However, a sensitive imaging technique for investigating the in vivo dynamics of transplanted stem cells has not yet been established and the mechanisms of stem cell-based therapy remain largely unexplored. In this study, we administered mouse adipose tissue-derived mesenchymal stem cells (mASCs) labeled with quantum dots (QDs; 8.0 nM) to a mouse model of bleomycin-induced pulmonary fibrosis in an effort to clarify the relationship between in vivo dynamics and therapeutic efficacy. These QD-labeled mASCs were injected into the trachea of C57BL/6 mice seven days after bleomycin administration to induce fibrosis in the lungs. The therapeutic effects and efficacy were evaluated via in vivo/ex vivo imaging, CT imaging, and H&E staining of lung sections. The QD-labeled mASCs remained in the lungs longer and suppressed fibrosis. The 3D imaging results showed that the transplanted cells accumulated in the peripheral and fibrotic regions of the lungs. These results indicate that mASCs may prevent fibrosis. Thus, QD labeling could be a suitable and sensitive imaging technique for evaluating in vivo kinetics in correlation with the efficacy of cell therapy.
Assuntos
Bleomicina , Modelos Animais de Doenças , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Camundongos Endogâmicos C57BL , Fibrose Pulmonar , Animais , Bleomicina/efeitos adversos , Bleomicina/toxicidade , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/terapia , Fibrose Pulmonar/patologia , Camundongos , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Pontos Quânticos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Tomografia Computadorizada por Raios X , Tecido Adiposo/citologia , Tecido Adiposo/diagnóstico por imagemRESUMO
BACKGROUND: Mesenchymal stem cells (MSCs)-based treatment strategy has shown promise in bolstering the healing process of chronic wounds in diabetic patients, who are at risk of amputation and mortality. To overcome the drawbacks of suboptimal cell retention and diminished cell viability at the injury site, a novel nanofibrous biomaterial-based scaffold was developed by using a controlled extrusion of a polymeric solution to deliver the cells (human adipose-derived MSCs (ADMSCs) and placenta-derived MSCs (PLMSCs)) locally to the animal model of diabetic ulcers. METHODS: The physicochemical and biological properties of the nano-bioscaffold were characterized in terms of microscopic images, FTIR spectroscopy, tensile testing, degradation and swelling tests, contact angle measurements, MTT assay, and cell attachment evaluation. To evaluate the therapeutic efficacy, a study using an excisional wound model was conducted on diabetic rats. RESULTS: The SEM and AFM images of scaffolds revealed a network of uniform nanofibers with narrow diameters between 100-130 nm and surface roughness less than 5 nm, respectively. ADMSCs and PLMSCs had a typical spindle-shaped or fibroblast-like morphology when attached to the scaffold. Desired characteristics in terms of swelling, hydrophilicity, biodegradation rate, and biocompatibility were achieved with the CS70 formulation. The wound healing process was accelerated according to wound closure rate assay upon treatment with MSCs loaded scaffold resulting in increased re-epithelialization, neovascularization, and less inflammatory reaction. Our findings unequivocally demonstrated that the cell-loaded nano-bioscaffold exhibited more efficacy compared with its acellular counterpart. In summation, our study underscores the potential of this innovative cellular scaffold as a viable solution for enhancing the healing of diabetic ulcers. CONCLUSION: The utilization of MSCs in a nanofibrous biomaterial framework demonstrates significant promise, providing a novel avenue for advancing wound care and diabetic ulcer management.
Assuntos
Quitosana , Diabetes Mellitus Experimental , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Nanofibras , Alicerces Teciduais , Cicatrização , Animais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Nanofibras/química , Ratos , Humanos , Diabetes Mellitus Experimental/terapia , Alicerces Teciduais/química , Quitosana/química , Transplante de Células-Tronco Mesenquimais/métodos , Feminino , Masculino , Gravidez , Tecido Adiposo/citologia , Placenta/citologiaRESUMO
BACKGROUND: Human adipose-derived stem cells (ADSCs) exert a strong anti-inflammatory effect, and synovium-derived stem cells (SDSCs) have high chondrogenic potential. Thus, this study aims to investigate whether a combination of human ADSCs and SDSCs will have a synergistic effect that will increase the chondrogenic potential of osteoarthritis (OA) chondrocytes in vitro and attenuate the cartilage degeneration of early and advanced OA in vitro. METHODS: ADSCs, SDSCs, and chondrocytes were isolated from OA patients who underwent total knee arthroplasty. The ADSCs-SDSCs mixed cell ratios were 1:0 (ADSCs only), 8:2, 5:5 (5A5S), 2:8, and 0:1 (SDSCs only). The chondrogenic potential of the OA chondrocytes was evaluated in vitro with a transwell assay or pellet culture with various mixed cell groups. The mixed cell group with the highest chondrogenic potential was then selected and injected into the knee joints of nude rats of early and advanced OA stages in vivo. The animals were then evaluated 12 and 20 weeks after surgery through gait analysis, von frey test, microcomputed tomography, MRI, and immunohistochemical and histological analyses. Finally, the mechanisms underlying these findings were investigated through the RNA sequencing of tissue samples in vivo and Western blot of the OA chondrocyte autophagy pathway. RESULTS: Among the MSCs treatment groups, 5A5S had the greatest synergistic effect that increased the chondrogenic potential of OA chondrocytes in vitro and inhibited early and advanced OA in vivo. The 5A5S group significantly reduced cartilage degeneration, synovial inflammation, pain sensation, and nerve invasion in subchondral nude rat OA, outperforming both single-cell treatments. The underlying mechanism was the activation of chondrocyte autophagy via the FoxO1 signaling pathway. CONCLUSION: A combination of human ADSCs and SDSCs demonstrated higher potential than a single type of stem cell, demonstrating potential as a novel treatment for OA.
Assuntos
Autofagia , Condrócitos , Proteína Forkhead Box O1 , Células-Tronco Mesenquimais , Osteoartrite , Transdução de Sinais , Humanos , Condrócitos/metabolismo , Animais , Ratos , Osteoartrite/terapia , Osteoartrite/metabolismo , Osteoartrite/patologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Proteína Forkhead Box O1/metabolismo , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Masculino , Ratos Nus , Condrogênese , Membrana Sinovial/metabolismo , Membrana Sinovial/citologia , Pessoa de Meia-Idade , FemininoRESUMO
BACKGROUND AND OBJECTIVE: Adipose-derived mesenchymal stem cells (ADSCs) can accelerate wound healing, reduce scar formation, and inhibit hypertrophic scar (HTS). ADSCs can secrete a large amount of CCL5, and CCL5 has been proved to be pro-inflammatory and pro-fibrotic. CXCL12 (SDF-1) is a key chemokine that promotes stem cell migration and survival. Therefore, this study selected normal skin and HTS conditioned medium to simulate different microenvironments, and analyzed the effects of different microenvironments on the expression of CCL5 and CXCL12 in human ADSCs (hADSCs). MATERIALS AND METHODS: hADSCs with silenced expression of CCL5 and CXCL12 were co-cultured with hypertrophic scar fibroblasts to verify the effects of CCL5 and CXCL12 in hADSCs on the proliferation ability of hypertrophic scar fibroblasts. A mouse model of hypertrophic scar was established to further confirm the effect of CCL5 and CXCL12 in hADSCs on hypertrophic scar formation. RESULTS: CCL5 level was found to be significantly high in hADSCs cultured in HTS conditioned medium. CXCL12 in HTS group was prominently lowly expressed compared with the normal group. Inhibition of CCL5 in hADSCs enhanced the effects of untreated hADSCs on proliferation of HTS fibroblasts while CXCL12 knockdown exerted the opposite function. Inhibition of CCL5 in hADSCs increased the percentage of HTS fibroblasts in the G0/G1 phase while down-regulation of CXCL12 decreased those. Meanwhile, the down-regulated levels of fibroblast markers including collagen I, collagen III, and α-SMA induced by CCL5 knockdown were significantly up-regulated by CXCL12 inhibition. hADSCs alleviate the HTS of mice through CCL5 and CXCL12. CONCLUSION: In summary, our results demonstrated that hADSCs efficiently cured HTS by suppressing proliferation of HTS fibroblasts, which may be related to the inhibition of CXCL12 and elevation of CCL5 in hADSCs, suggesting that hADSCs may provide an alternative therapeutic approach for the treatment of HTS.
Assuntos
Proliferação de Células , Quimiocina CCL5 , Quimiocina CXCL12 , Cicatriz Hipertrófica , Fibroblastos , Células-Tronco Mesenquimais , Quimiocina CCL5/metabolismo , Fibroblastos/metabolismo , Humanos , Cicatriz Hipertrófica/patologia , Cicatriz Hipertrófica/metabolismo , Células-Tronco Mesenquimais/metabolismo , Animais , Quimiocina CXCL12/metabolismo , Camundongos , Modelos Animais de Doenças , Células Cultivadas , Feminino , Meios de Cultivo Condicionados/farmacologia , Técnicas de Cocultura , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Adulto , Cicatrização , Tecido Adiposo/citologiaRESUMO
BACKGROUND: Fat grafting is a highly versatile option in the reconstructive armamentarium but with unpredictable retention rates and outcomes. The primary outcome of this systematic review was to assess whether secondary mechanically processed lipoaspirate favorably enhances the vasculogenic potential of fat grafts when compared to unprocessed lipoaspirate or fat grafts prepared using centrifugation alone. The secondary outcome was to assess the evidence around graft retention and improved outcomes when comparing the aforementioned groups. METHODS: A search on MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials was conducted up to February 2022. All human and animal research, which provided a cross-comparison between unprocessed, centrifuged, secondary mechanically fragmented (SMF) or secondary mechanically disrupted (SMD) fat grafts, was included. RESULTS: Thirty-one full texts were included. Vasculogenic potential was assessed by quantification of angiogenic growth factors and cellular composition. Cellular composition of mesenchymal stem cells, perivascular stem cells, and endothelial progenitor cells was quantified by fluorescence activated cell sorting (FACS) analysis. Fat graft volume retention rates and fat grafting to aid wound healing were assessed. Although the presence of industry-funded studies and inadequate reporting of methodological data in some studies were sources of bias, data showed SMF grafts contain an enriched pericyte population with increased vascular endothelial growth factor (VEGF) secretion. Animal studies indicate that SMD grafts may increase rates of fat graft retention and wound closure compared to centrifuged grafts; however, clinical studies are yet to show similar results. CONCLUSIONS: In this systematic review, we were able to conclude that the existing literature suggests mechanically processing fat, whether it be through fragmentation or disruption, improves vasculogenic potential by enhancing angiogenic growth factor and relevant vascular progenitor cell levels. Whilst in vivo animal studies are scarce, the review findings suggest that secondary mechanically processed fat enhances fat graft retention and can aid with wound healing. Further clinical studies are required to assess potential differences in human studies.
Assuntos
Tecido Adiposo , Lipectomia , Humanos , Tecido Adiposo/transplante , Lipectomia/métodos , Neovascularização Fisiológica/fisiologia , Sobrevivência de Enxerto , AnimaisRESUMO
Psoriasis (Ps) is one of the most common chronic inflammatory skin disorders with its pathogenesis correlated with dysregulated innate and adaptive system. Even though biological agents have advanced the treatment of psoriasis, however, there are huge limitations, like high adverse reactions and relapse rate. Therefore, it is of great interest in searching clinical resolutions with better safety and efficacy. In the current study, we utilized the adipose-derived mesenchymal stem cell (AD-MSCs) to treat moderate/severe cases of psoriasis in a single-arm clinical study. This AD-MSC treatment has proven to be clinically safe and effective. Interestingly, a trend of adaptome improvement, including increased diversity, elevated uCDR3s and decreased large clone after AD-MSC treatment in a short (2 weeks) and long (12 weeks) terms. In conclusion, allogenic AD-MSC treatment has shown a good safety and efficacy in treating Ps and can effectively improve the compromised adaptive immune system of Ps patients.
Assuntos
Imunidade Adaptativa , Tecido Adiposo , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Psoríase , Humanos , Psoríase/terapia , Psoríase/imunologia , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Adulto , Tecido Adiposo/citologia , Masculino , Feminino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem , Pele/patologia , Pele/imunologia , Células Cultivadas , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Fat grafting and repositioning may serve as a convenient, economical, and effective surgical method for correcting lower eyelid pouch with a tear trough deformity or lid-cheek junction. However, comprehensive systematic reviews and meta-analyses investigating the complications associated with this technique are lacking. OBJECTIVE: This study aimed to summarize and gather data on complications related to fat grafting and repositioning for the correction of tear trough deformity or lid-cheek junction in lower eyelid blepharoplasty. METHODS: A thorough search was performed across multiple databases including PubMed, Cochrane, Embase, ProQuest, Ovid, Scopus, and Web of Science. Specific inclusion and exclusion criteria were applied to screen the articles. The occurrence of complications was analyzed using a random-effects model. RESULTS: A total of 33 studies involving 4671 patients met the criteria for systematic evaluation and were included in this meta-analysis. The overall complication rates were 0.112 (95% confidence interval [CI]: 0.060-0.177) for total complications, 0.062 (95% CI: 0.003-0.172) for unsatisfactory correction or contour irregularity, 0.062 (95% CI: 0.009-0.151) for hematoma, swelling (not specified as bulbar conjunctiva), ecchymosis, or oozing of blood, and 0.024 (95% CI: 0.013-0.038) for reoperation. CONCLUSIONS: Fat grafting and repositioning for correcting a lower eyelid pouch with tear trough deformity or lid-cheek junction was associated with high rates of complications. Therefore, it is crucial to closely monitor the rates of unsatisfactory correction or contour irregularity, hematoma, swelling (not specified as bulbar conjunctiva), ecchymosis, or oozing of blood, and reoperation. In addition, effective communication with patients should be prioritized.
Assuntos
Tecido Adiposo , Blefaroplastia , Complicações Pós-Operatórias , Humanos , Blefaroplastia/métodos , Tecido Adiposo/transplante , Complicações Pós-Operatórias/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pálpebras/cirurgia , Bochecha/cirurgiaRESUMO
Plasma growth differentiation factor-15 (GDF-15) levels increase with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) but the underlying mechanism remains poorly defined. Using male mouse models of obesity and MASLD, and biopsies from carefully-characterized patients regarding obesity, type 2 diabetes (T2D) and MASLD status, we identify adipose tissue (AT) as the key source of GDF-15 at onset of obesity and T2D, followed by liver during the progression towards metabolic dysfunction-associated steatohepatitis (MASH). Obesity and T2D increase GDF15 expression in AT through the accumulation of macrophages, which are the main immune cells expressing GDF15. Inactivation of Gdf15 in macrophages reduces plasma GDF-15 concentrations and exacerbates obesity in mice. During MASH development, Gdf15 expression additionally increases in hepatocytes through stress-induced TFEB and DDIT3 signaling. Together, these results demonstrate a dual contribution of AT and liver to GDF-15 production in metabolic diseases and identify potential therapeutic targets to raise endogenous GDF-15 levels.
Assuntos
Tecido Adiposo , Diabetes Mellitus Tipo 2 , Fígado Gorduroso , Fator 15 de Diferenciação de Crescimento , Hepatócitos , Macrófagos , Obesidade , Fator 15 de Diferenciação de Crescimento/metabolismo , Fator 15 de Diferenciação de Crescimento/genética , Animais , Obesidade/metabolismo , Obesidade/patologia , Hepatócitos/metabolismo , Masculino , Macrófagos/metabolismo , Camundongos , Humanos , Tecido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Fígado/patologia , Modelos Animais de Doenças , Transdução de SinaisRESUMO
Bone marrow adipose tissue (BMAT) is a metabolically and clinically relevant fat depot that exists within bone. Two subtypes of BMAT, regulated and constitutive, reside in hematopoietic-rich red marrow and fatty yellow marrow, respectively, and exhibit distinct characteristics compared to peripheral fat such as white and brown adipose tissues. Bone marrow adipocytes (BMAds) are evolutionally preserved in most vertebrates, start development after birth and expand throughout life, and originate from unique progenitor populations that control bone formation and hematopoiesis. Mature BMAds also interact closely with other cellular components of the bone marrow niche, serving as a nearby energy reservoir to support the skeletal system, a signaling hub that contributes to both local and systemic homeostasis, and a final fuel reserve for survival during starvation. Though BMAT and bone are often inversely correlated, more BMAT does not always mean less bone, and the prevention of BMAT expansion as a strategy to prevent bone loss remains questionable. BMAT adipogenesis and lipid metabolism are regulated by the nervous systems and a variety of circulating hormones. This contributes to the plasticity of BMAT, including BMAT expansion in common physiological or pathological conditions, and BMAT catabolism under certain extreme circumstances, which are often associated with malnutrition and/or systemic inflammation. Altogether, this article provides a comprehensive overview of the local and systemic functions of BMAT and discusses the regulation and plasticity of this unique adipose tissue depot in health and disease. © 2024 American Physiological Society. Compr Physiol 14:5521-5579, 2024.
Assuntos
Tecido Adiposo , Medula Óssea , Humanos , Animais , Medula Óssea/metabolismo , Medula Óssea/fisiologia , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiologia , Adipócitos/metabolismo , Adipócitos/fisiologia , Adipogenia/fisiologiaRESUMO
Tissue-resident macrophages (TRMs) are an integral part of the innate immune system, but their biology is not well understood in the context of cancer. Distinctive resident macrophage populations are identified in different organs in mice using fate mapping studies. They develop from the yolk sac and self-maintain themselves lifelong in specific tissular niches. Similarly, breast-resident macrophages are part of the mammary gland microenvironment. They reside in the breast adipose tissue stroma and close to the ductal epithelium and help in morphogenesis. In breast cancer, TRMs may promote disease progression and metastasis; however, precise mechanisms have not been elucidated. TRMs interact intimately with recruited macrophages, cytotoxic T cells, and other immune cells along with cancer cells, deciding further immunosuppressive or cytotoxic pathways. Moreover, triple-negative breast cancer (TNBC), which is generally associated with poor outcomes, can harbor specific TRM phenotypes. The influence of TRMs on adipose tissue stroma of the mammary gland also contributes to tumor progression. The complex crosstalk between TRMs with T cells, stroma, and breast cancer cells can establish a cascade of downstream events, understanding which can offer new insight for drug discovery and upcoming treatment choices. This review aims to acknowledge the previous research done in this regard while exploring existing research gaps and the future therapeutic potential of TRMs as a combination or single agent in breast cancer.
Assuntos
Neoplasias da Mama , Macrófagos , Microambiente Tumoral , Humanos , Animais , Feminino , Microambiente Tumoral/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Tecido Adiposo/citologia , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
BACKGROUND: In the repair of massive tissue defects using expanded large skin flaps, the incidence of complications increases with the size of the expanded area. Currently, stem cell therapy has limitations to solve this problem. We hypothesized that conditioned medium of adipose-derived stem cells (ADSC-CM) collected following mechanical pretreatment can assist skin expansion. METHODS: Rat aortic endothelial cells and fibroblasts were cultured with ADSC-CM collected under 0%, 10%, 12%, and 15% stretching force. Ten-milliliter cylindrical soft tissue expanders were subcutaneously implanted into the backs of 36 Sprague-Dawley rats. The 0% and 10% stretch groups were injected with ADSC-CM collected under 0% and 10% stretching force, respectively, while the control group was not injected. After 3, 7, 14, and 30 days of expansion, expanded skin tissue was harvested for staining and qPCR analyses. RESULTS: Endothelial cells had the best lumen formation and highest migration rate, and fibroblasts secreted the most collagen upon culture with ADSC-CM collected under 10% stretching force. The skin expansion rate was significantly increased in the 10% stretch group. After 7 days of expansion, the number of blood vessels in the expanded area, expression of the angiogenesis-associated proteins vascular endothelial growth factor, basic fibroblast growth factor, and hepatocyte growth factor, and collagen deposition were significantly increased in the 10% stretch group. CONCLUSIONS: The optimal mechanical force upregulates specific paracrine proteins in ADSCs to increase angiogenesis and collagen secretion, and thereby promote skin regeneration and expansion. This study provides a new auxiliary method to expand large skin flaps.
Assuntos
Tecido Adiposo , Comunicação Parácrina , Ratos Sprague-Dawley , Pele , Animais , Ratos , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Pele/metabolismo , Fibroblastos/metabolismo , Fibroblastos/citologia , Células Endoteliais/metabolismo , Células Endoteliais/citologia , Meios de Cultivo Condicionados/farmacologia , Expansão de Tecido/métodos , Masculino , Células-Tronco/metabolismo , Células-Tronco/citologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Células Cultivadas , Neovascularização Fisiológica , Estresse MecânicoRESUMO
Olfactory-ensheathing cells (OECs) are known for their role in neuronal regeneration and potential to promote tissue repair. Adipose-derived stem cells (ADSCs), characterized by mesenchymal stem cell (MSC) traits, display a fibroblast-like morphology and express MSC surface markers, making them suitable for regenerative therapies for osteoarthritis (OA). In this study, OECs and ADSCs were derived from tissues and characterized for their morphology, surface marker expression, and differentiation capabilities. Collagenase-induced OA was created in 10-week-old C57BL/6 mice, followed by intra-articular injections of ADSCs (1 × 105), OECs (1 × 105), or a higher dose of OECs (5 × 105). Therapeutic efficacy was evaluated using rotarod performance tests, MRI, histology, and immunohistochemistry. Both cell types exhibited typical MSC characteristics and successfully differentiated into adipocytes, osteoblasts, and chondrocytes, confirmed by gene expression and staining. Transplantation significantly improved rotarod performance and preserved cartilage integrity, as seen in MRI and histology, with reduced cartilage destruction and increased chondrocytes. Immunohistochemistry showed elevated type II collagen and aggrecan in treated joints, indicating hyaline cartilage formation, and reduced MMP13 and IL-1ß expression, suggesting decreased inflammation and catabolic activity. These findings highlight the regenerative potential of OECs and ADSCs in treating OA by preserving cartilage, promoting chondrocyte proliferation, and reducing inflammation. Further research is needed to optimize delivery methods and evaluate long-term clinical outcomes.
Assuntos
Tecido Adiposo , Camundongos Endogâmicos C57BL , Osteoartrite , Animais , Osteoartrite/terapia , Osteoartrite/patologia , Tecido Adiposo/citologia , Camundongos , Diferenciação Celular , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Bulbo Olfatório/citologia , Masculino , Células-Tronco/citologia , Células-Tronco/metabolismoRESUMO
Hepatocyte organoids (HOs) have superior hepatic functions to cholangiocyte-derived organoids but suffer from shorter lifespans. To counteract this, we co-cultured pig HOs with adipose-derived mesenchymal stem cells (A-MSCs) and performed transcriptome analysis. The results revealed that A-MSCs enhanced the collagen synthesis pathways, which are crucial for maintaining the three-dimensional structure and extracellular matrix synthesis of the organoids. A-MSCs also increased the expression of liver progenitor cell markers (KRT7, SPP1, LGR5+, and TERT). To explore HOs as a liver disease model, we exposed them to alcohol to create an alcoholic liver injury (ALI) model. The co-culture of HOs with A-MSCs inhibited the apoptosis of hepatocytes and reduced lipid accumulation of HOs. Furthermore, varying ethanol concentrations (0-400 mM) and single-versus-daily exposure to HOs showed that daily exposure significantly increased the level of PLIN2, a lipid storage marker, while decreasing CYP2E1 and increasing CYP1A2 levels, suggesting that CYP1A2 may play a critical role in alcohol detoxification during short-term exposure. Moreover, daily alcohol exposure led to excessive lipid accumulation and nuclear fragmentation in HOs cultured alone. These findings indicate that HOs mimic in vivo liver regeneration, establishing them as a valuable model for studying liver diseases, such as ALI.
Assuntos
Apoptose , Técnicas de Cocultura , Hepatócitos , Regeneração Hepática , Células-Tronco Mesenquimais , Organoides , Células-Tronco Mesenquimais/metabolismo , Animais , Hepatócitos/metabolismo , Hepatócitos/patologia , Organoides/metabolismo , Apoptose/efeitos dos fármacos , Suínos , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Etanol , Fígado Gorduroso/patologia , Fígado Gorduroso/metabolismo , Hepatopatias Alcoólicas/patologia , Hepatopatias Alcoólicas/metabolismo , Metabolismo dos LipídeosRESUMO
Adipose tissue dysfunction, which is associated with an increased risk of colorectal cancer (CRC), is a significant factor in the pathophysiology of obesity. Obesity-related inflammation and extracellular matrix (ECM) remodeling promote colorectal cancer metastasis (CRCM) by shaping the tumor microenvironment (TME). When CRC occurs, the metabolic symbiosis of tumor cells recruits adjacent adipocytes into the TME to supply energy. Meanwhile, abundant immune cells, from adipose tissue and blood, are recruited into the TME, which is stimulated by pro-inflammatory factors and triggers a chronic local pro-inflammatory TME. Dysregulated ECM proteins and cell surface adhesion molecules enhance ECM remodeling and further increase contractibility between tumor and stromal cells, which promotes epithelial-mesenchymal transition (EMT). EMT increases tumor migration and invasion into surrounding tissues or vessels and accelerates CRCM. Colorectal symbiotic microbiota also plays an important role in the promotion of CRCM. In this review, we provide adipose tissue and its contributions to CRC, with a special emphasis on the role of adipocytes, macrophages, neutrophils, T cells, ECM, and symbiotic gut microbiota in the progression of CRC and their contributions to the CRC microenvironment. We highlight the interactions between adipocytes and tumor cells, and potential therapeutic approaches to target these interactions.