Search Results (190)

Bone-related defects present a key challenge in orthopaedics. The current gold standard, autografts, poses significant limitations, such as donor site morbidity, limited supply, and poor morphological adaptability. This study investigates the potential of scaffold geometry to induce osteogenic differentiation of human adipose-derived stem cells (hADSCs) through mechanotransduction, without the use of chemical inducers. Four distinct poly-(L)-lactic acid (PLA) scaffold architectures—Traditional Cross (Tc), Triangle (T), Diamond (D), and Gyroid (G)—were fabricated using fused filament fabrication (FFF) 3D printing. hADSCs were cultured on these scaffolds, and their response was evaluated utilising an alkaline phosphatase (ALP) assay, immunofluorescence, and extensive proteomic analyses. The results showed the D scaffold to have the highest ALP activity, followed by Tc. Proteomics results showed that more than 1200 proteins were identified in each scaffold with unique proteins expressed in each scaffold, respectively Tc—204, T—194, D—244, and G—216. Bioinformatics analysis revealed structures with complex curvature to have an increased expression of proteins involved in mid- to late-stage osteogenesis signalling and differentiation pathways, while the Tc scaffold induced an increased expression of signalling and differentiation pathways pertaining to angiogenesis and early osteogenesis. Full article

Background: Chronic wounds represent a persistent clinical challenge and impose a considerable burden on healthcare systems. These lesions often require multidisciplinary management due to underlying factors such as microbial colonization, impaired immunity, and vascular insufficiencies. Regenerative therapies, particularly autologous approaches, have emerged as promising strategies to enhance wound healing. Adipose tissue-derived stem cells (ADSCs) and platelet-rich plasma (PRP) may improve outcomes through paracrine effects and growth factor release. Methods: A prospective observational study was conducted on 31 patients with chronic wounds that were unresponsive to conservative treatment for over six weeks. Clinical and photographic evaluations were employed to monitor healing. All patients underwent surgical debridement, with adjunctive interventions—negative pressure wound therapy, grafting, or flaps—applied as needed. PRP infiltration and/or autologous adipose tissue transfer were administered based on wound characteristics. Wound area reduction was the primary outcome measure. Results: The cohort included 17 males and 14 females (mean age: 59 years). Etiologies included venous insufficiency (39%), diabetes mellitus (25%), arterial insufficiency (16%), and trauma (16%). Most lesions (84%) were located on the lower limbs. All patients received PRP therapy; five underwent combined PRP and fat grafting. Over the study period, 64% of the patients exhibited >80% wound area reduction, with complete healing in 48.3% and a mean healing time of 49 days. Conclusions: PRP therapy proved to be a safe, effective, and adaptable treatment, promoting substantial healing in chronic wounds. Autologous adipose tissue transfer did not confer additional benefit. PRP may warrant inclusion in national treatment protocols. Full article

Radiation therapy, a highly effective cancer treatment that targets cancer cells, may produce challenging side effects, including radiation-induced skin tissue injuries. The wound healing process involves complex cellular responses, with key phases including hemostasis, inflammation, proliferation, and remodeling. However, radiation-induced injuries disrupt this process, resulting in delayed healing, excessive scarring, and compromised tissue integrity. This review explores innovative approaches related to wound healing in post-radiotherapy defects, focusing on the integration of adipose-derived stem cells (ADSCs) in protein/polysaccharide bioengineered scaffolds. Such scaffolds, like hydrogels, sponges, or 3D-printed/bioprinted materials, provide a biocompatible and biomimetic environment that supports cell-to-cell and cell-to-matrix interactions. Various proteins and polysaccharides are discussed for beneficial properties and limitations, and their compatibility with ADSCs in wound healing applications. The potential of ADSCs-polymeric scaffold combinations in radiation-induced wound healing is investigated, alongside the mechanisms of cell proliferation, inflammation reduction, angiogenesis promotion, collagen formation, integrin binding, growth factor signaling, and activation of signaling pathways. New strategies to improve the therapeutic efficacy of ADSCs by integration in adaptive polymeric materials and designed scaffolds are highlighted, providing solutions for radiation-induced wounded skin, personalized care, faster tissue regeneration, and, ultimately, enhanced quality of the patients’ lives. Full article

Cultivated meat, developed through cell culture technology, is emerging as a promising solution that closely mimics both the flavor and nutrient profiles of conventional meat. One key component that contributes to the flavor of meat is fat content. In this study, bovine adipose-derived stem cells (bADSCs) were cultured for the production of alternative fat in vitro. The expression of mesenchymal stem cell (MSC) markers (CD29, CD73, and CD105) and colony forming efficiency were assessed to characterize bADSCs. bADSCs were differentiated into adipocytes to produce cultivated fat in 2D or 3D culture. The cultivated fat was analyzed by gas chromatography to verify the similarity of the fatty acids of animal-derived fat. Our results show that bADSCs have characteristics of MSC and could differentiate into adipocyte. The ratio of unsaturated fatty acids and saturated fatty acids in cultivated fat and adipose tissue was similar. Adipogenic differentiation of ADSCs using a textured vegetable protein (TVP) scaffold could form the lipid droplets in the TVP. This study demonstrated the establishment of a culture system for the fat production from bADSCs in vitro. The fat produced through bADSCs shows the potential to be used in the composition of hybrid-cultivated meat. Full article

The global obese population accounts for approximately 30% of the total population and continues to increase. White adipocytes, which accumulate in the body for energy storage, are associated with obesity. Mechanisms that activate browning of white adipocytes are an attractive therapeutic target for obesity and metabolic disorders. Exosomes are nano-sized biovesicles that play a role in cell-to-cell communication though the transfer of cargos such as microRNAs. Although milk exosomes contain many endogenous microRNA molecules, the role of microRNAs in milk exosomes is limited. Therefore, the aim of this study was to investigate the effects of milk exosomes on the browning of white adipocyte. Mouse pre-adipocytes (3T3-L1) and human adipose-derived stem cells (hADSCs) were differentiated and exposed to milk exosomes. Compared to control, milk exosomes promoted the expression of thermogenic genes and cellular mitochondrial energy metabolism in both 3T3-L1 cells and hADSCs. Additionally, milk exosomes were orally administered to mice fed a high-fat diet. As the intake of milk exosomes increased, the mice’s body weight decreased. Milk exosomes also increased the protein levels of thermogenic genes and mitochondrial-related genes in mouse adipose tissue. The overexpression of miR-11987, which is abundant in milk exosomes, in both 3T3-L1 cells and hADSCs led to the increased expression of thermogenic genes and mitochondrial activity. Our results support that bovine-specific miR-11987 in milk exosomes promotes the browning of white adipocytes. Therefore, milk exosome and milk exosomal miR-11987 could have significant clinical implications for obesity and metabolic syndrome. Full article

Osteoarthritis (OA) is a prevalent and debilitating joint disorder that affects a substantial proportion of the global population, underscoring the urgent need for therapeutic strategies that extend beyond symptomatic management. Although mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality, their clinical application remains constrained by several inherent limitations. This study explores a cell-free alternative by investigating the therapeutic potential of exosomes derived from bone marrow (BMSCs), adipose tissue (ADSCs), and umbilical cord (UMSCs) MSCs in mitigating OA pathogenesis, utilizing both in vitro and ex vivo models. Exosomes from each MSC source were isolated and characterized through nanoparticle tracking analysis, transmission electron microscopy, and Western blotting to confirm their identity and purity. Subsequently, their chondroprotective, anti-inflammatory, and regenerative properties were systematically assessed through evaluations of cell viability, expression profiles of inflammatory and chondroprotective markers, and chondrocyte migration assays. The results demonstrate that all three types of MSC-derived exosomes (MSC-Exos) exhibit low cytotoxicity while significantly suppressing proinflammatory markers and enhancing the expression of chondroprotective genes. Notably, BMSC-Exos and UMSC-Exos displayed superior efficacy in attenuating inflammation, promoting cartilage protection, and inhibiting chondrocyte apoptosis. Furthermore, all MSC-Exos markedly enhanced chondrocyte motility, a critical component of cartilage repair. Collectively, these findings support the therapeutic promise of MSC-Exos, particularly those derived from BMSCs and UMSCs, as a targeted, cell-free approach for the treatment of OA compared to ADSCs. By modulating inflammation, promoting cartilage regeneration, and preventing chondrocyte apoptosis, MSC-Exos may serve as a viable and scalable alternative to current MSC-based therapies for this widespread degenerative disease. Full article

Tendon ruptures and tendinopathies represent a major part of musculoskeletal injuries. Due to the hypovascular and hypocellular nature of tendons, the natural healing capacity is slow and limited. Cell-free approaches for tendon injuries are being investigated as the next generation of therapeutic treatments. The aim of this study was to compare the proteomic profiles and biological activities of two different secretomes, obtained from New Zealand white rabbit adipose-tissue-derived mesenchymal stem cells (ADSCs) or a 3:1 mixed culture of ADSCs and rabbit tenocytes. The secretomes were analyzed by liquid chromatography–tandem mass spectrometry (LC–MS/MS) and their functional properties, such as gene expression, migration and angiogenesis, were investigated in vitro in rabbit tenocytes and in ovo using the chicken chorioallantoic membrane (CAM) assay after stimulation with secretomes or medium control. Both secretomes had a positive effect on angiogenesis and showed similar changes in relative gene expression levels associated with extracellular matrix (ECM) remodeling. Proteomic data showed that the two secretomes were clearly distinguishable, with 182 proteins significantly differentially expressed. The ADSC secretome was more effective in enhancing tenocyte migration under both healthy and inflammatory conditions. In the upregulated protein fraction of the mixed secretome, the tendon-related protein biglycan (BGN) and tenascin C (TNC) were increased. Based on our results, the mixed secretome shows great potential for promoting tendon healing as its composition is more effective in enhancing ECM-related processes and tendon development than the secretome of ADSCs. Full article

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by vasculopathy and tissue fibrosis affecting the skin and internal organs. Genetic and environmental factors influence susceptibility, severity, and onset. Current treatments are limited and not always effective, leading researchers to investigate new approaches, such as the use of adipose-derived mesenchymal stem cells (ADSCs) through fat grafting. This review seeks to understand how ADSCs may impact the development and progression of SSc, with a particular focus on how these cells could alter immune responses and reduce fibrosis. ADSCs have been found to affect various immune cells, including T cells, B cells, macrophages, and dendritic cells, by releasing cytokines, chemokines, and growth factors. These interactions generally suppress inflammation and promote a regulatory immune environment. Additionally, ADSCs can influence the extracellular matrix, helping to prevent fibrosis through signaling molecules like exosomes. ADSCs show promise as a treatment for SSc due to their ability to modulate the immune system and reduce fibrosis. Early clinical studies are encouraging, but more research is needed to fully understand how they work and to develop effective treatment protocols. Full article

Effective bladder reconstruction remains a significant challenge in urology, particularly for conditions requiring partial or complete bladder replacement. In this study, the efficacy is evaluated of two types of scaffolds, silk fibroin (SF) and adipose-derived stem cells (ADSCs-SF), in promoting bladder regeneration and their associated outcomes. A rat model was used to compare the surgical outcomes and morphological recovery of bladder tissues implanted with SF and ADSCs-SF scaffolds. Post-operative recovery, including voiding ability and complication rates, was assessed. The morphological and histological changes of the regenerated bladder tissue were evaluated at multiple time points (2, 4, 8, and 12 weeks) using gross tissue analysis, histometric assessments, and immunohistochemical staining. Both scaffold types demonstrated successful integration into the bladder wall with no significant differences in body weight or voiding issues. The SF scaffold group exhibited graft shrinkage and a 41.6% incidence of bladder calculus formation. In contrast, the ADSCs-SF scaffold facilitated superior morphological restoration, with bladder tissue progressively adopting a more normal shape and no incidence of bladder calculus. Histological analysis revealed that the ADSCs-SF scaffold significantly promoted the regeneration of a more organized urothelium layer and smooth muscle tissue. It also resulted in higher vessel density and reduced infiltration of inflammatory cells when compared to the SF scaffold alone. Additionally, the ADSCs-SF group exhibited enhanced expression of key markers, including uroplakin III, a urothelial marker, and α-SMA, a smooth muscle cell marker. These findings suggest that the ADSCs-SF scaffold not only supports the structural integrity of the bladder but also improves tissue regeneration and reduces adverse inflammatory responses, offering a promising approach for bladder repair and reconstruction. Full article

Peripheral nerve injuries are common complications in surgical and dental practices, often resulting in functional deficiencies and reduced quality of life. Current treatment choices, such as autografts, have limitations, including donor site morbidity and suboptimal outcomes. Adipose-derived stem cells (ADSCs) have shown assuring regenerative potential due to their accessibility, ease of harvesting and propagation, and multipotent properties. This review investigates the therapeutic potential of ADSCs in peripheral nerve regeneration, focusing on their use in bioengineered nerve conduits and supportive microenvironments. The analysis is constructed on published case reports, organized reviews, and clinical trials from Phase I to Phase III that investigate ADSCs in managing nerve injuries, emphasizing both peripheral and orofacial applications. The findings highlight the advantages of ADSCs in promoting nerve regeneration, including their secretion of angiogenic and neurotrophic factors, support for cellular persistence, and supplementing scaffold-based tissue repair. The regenerative capabilities of ADSCs in peripheral nerve injuries offer a novel approach to augmenting nerve repair and functional recovery. The accessibility of adipose tissue and the minimally invasive nature of ADSC harvesting further encourage its prospective application as an autologous cell source in regenerative medicine. Future research is needed to ascertain standardized protocols and optimize clinical outcomes, paving the way for ADSCs to become a mainstay in nerve regeneration. Full article

Mesenchymal stem cells (MSCs) are a family of multipotent stem cells that show self-renewal under proliferation, multilineage differentiation, immunomodulation, and trophic function. Thus, these cells, such as adipose tissue-derived mesenchymal stem cells (ADSCs), bone marrow-derived MSCs (BM-MSCs), and umbilical cord-derived mesenchymal stem cells (UC-MSCs), carry great promise for novel clinical treatment options. However, the challenges associated with the isolation of MSCs and the instability of their in vitro expansion remain significant barriers to their clinical application. The plasma membrane-spanning P-glycoprotein ATP-binding cassette subfamily B member 5 positive MSCs (ABCB5⁺ MSCs) derived from human skin specimens offer a distinctive advantage over other MSCs. They can be easily extracted from the dermis and expanded. In culture, ABCB5⁺ MSCs demonstrate robust innate homeostasis and a classic trilineage differentiation. Additionally, their ability to modulate the recipients’ immune system highlights their potential for allogeneic applications in regenerative medicine. In this review, we primarily discuss the differentiation potential of ABCB5⁺ MSCs and their perspectives in regenerative medicine. Full article

The application of regenerative therapy through stem cell transplantation has emerged as a promising avenue for the treatment of diabetes mellitus (DM). Transplanted tissue homeostasis is affected by disturbances in the clock genes of stem cells. The aim of this study is to investigate the diurnal variation in mitochondrial genes and function after transplantation of adipose-derived mesenchymal stem cells (T2DM-ADSCs) from type 2 diabetic patients into immunodeficient mice. Diurnal variation in mitochondrial genes was assessed by next-generation sequencing. As a result, the diurnal variation in mitochondrial genes showing troughs at ZT10 and ZT22 was observed in the group transplanted with adipose-derived mesenchymal stem cells derived from healthy individuals (N-ADSC). On the other hand, in the group transplanted with T2DM-ADSCs, diurnal variation indicative of troughs was observed at ZT18, with a large phase and amplitude deviation between the two groups. To evaluate the diurnal variation in mitochondrial function, we quantified mitochondrial DNA copy number using the Human mtDNA Monitoring Primer Set, measured mitochondrial membrane potential using JC-1, and evaluated mitophagy staining. The results showed a diurnal variation in mitochondrial DNA copy number, mitophagy, mitochondrial membrane potential, and NF-kB signaling in the N-ADSC transplant group. In contrast, no diurnal variation was observed in T2DM-ADSC transplants. The diurnal variation in mitochondrial function revealed in this study may be a new marker for the efficiency of T2DM-ADSC transplantation. Full article

The skin functions as the body’s primary defense barrier; when compromised, it can lead to dehydration, infection, shock, or potentially life-threatening conditions. Miniature pigs exhibit skin characteristics and healing processes highly analogous to humans. Mesenchymal stem cells contribute to skin injury repair through a paracrine mechanism involving exosomes. This research examines whether adipose-derived MSC exosomes effectively enhance healing following autologous skin grafting in miniature pigs. It also compares the roles and distinctions of ADSCs and ADSC-Exos in inflammatory responses and tissue regeneration. This study found significantly reduced levels of oxidative stress products and pro-inflammatory factors, while antioxidant factors, anti-inflammatory factors, and pro-regenerative factors were elevated, and anti-regenerative factor levels decreased. Moreover, the expression levels of key markers—namely, PI3K, Akt, and mTOR—in the regeneration-associated signaling pathway were increased. The alterations in these indicators indicate that ADSC-Exos can regulate inflammatory responses and promote regeneration. This study provides a novel theoretical foundation for the implementation of acellular therapy in clinical settings. Full article

Background/Objectives: Research on the roles of stem cells in necrotizing enterocolitis (NEC) has primarily focused on the effects of bone marrow- and amniotic fluid-derived stem cells in mitigating the clinical manifestations of the disease. However, the potential of adipose tissue-derived stem cells (ADSCs) remains unexplored in this context. The aim of this study was to evaluate the therapeutic potential of ADSC administration during the active inflammatory phase of NEC, with a specific focus on reducing the levels of the inflammatory cytokines IL-1 and IL-6. Methods: A self-modified hypoxia–hypothermia–formula feeding rat NEC model was employed. A total of 117 rat pups were divided into two groups: a treatment group (NEC-ADSC, n = 55) and a control group (NEC-PLCB (placebo), n = 62). In the NEC-ADSC group, ADSCs were administered intraperitoneally 24 h into the NEC protocol. After 72 h, bowel and fluid samples were collected for analysis. Results: The analysis revealed no significant effect on NEC histopathology (p = 0.347) or on the levels of IL-1 and IL-6 (p = 0.119 and p = 0.414, respectively). Conclusions: The administration of adipose tissue-derived stem cells after the onset of necrotizing enterocolitis does not reduce the levels of inflammatory cytokines IL-1 and IL-6, nor does it influence the histopathological outcomes of the disease in the rat model. Further research is needed to explore the potential therapeutic role of adipose tissue-derived stem cells in the treatment of necrotizing enterocolitis. Full article

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities, including visceral obesity, dyslipidemia, and insulin resistance. In this regard, visceral white adipose tissue (vWAT) plays a critical role, influencing energy metabolism, immunomodulation, and oxidative stress. Adipose-derived stem cells (ADSCs) are key players in these processes within vWAT. While second-generation antipsychotics (SGAs) have significantly improved treatments for mental health disorders, their chronic use is associated with an increased risk of MetS. In this study, we explored the impact of SGAs on ADSCs to better understand their role in MetS and identify potential therapeutic targets. Our findings reveal that olanzapine disrupts lipid droplet formation during adipogenic differentiation, impairing insulin receptor endocytosis, turnover, and signaling. SGAs also alter the endolysosomal compartment, leading to acidic vesicle accumulation and increased lysosomal biogenesis through TFEB activation. PKCζ is crucial for the SGA-induced nuclear translocation of TFEB and acidic vesicle formation. Notably, inhibiting PKCζ restored insulin receptor tyrosine phosphorylation, normalized receptor turnover, and improved downstream signaling following olanzapine treatment. This activation of PKCζ by olanzapine is driven by increased phosphatidic acid synthesis via phospholipase D (PLD), following G protein-coupled receptor (GPCR) signaling activation. Overall, olanzapine and clozapine disrupt endolysosomal homeostasis and insulin signaling in a PKCζ-dependent manner. These findings highlight SGAs as valuable tools for uncovering cellular dysfunction in vWAT during MetS and may guide the development of new therapeutic strategies to mitigate the metabolic side effects of these drugs. Full article