Search Results (196)

Background: Knee osteoarthritis (KOA) is a major cause of disability worldwide, and adipose-derived stromal vascular fraction (SVF) has emerged as a potential regenerative treatment to modify disease progression. Objective: This study aimed to assess the effectiveness of autologous adipose-derived stromal vascular fraction (SVF) through intra-articular injection to treat early-stage knee osteoarthritis (KOA). Materials and Methods: This multicenter observational study (2019–2023) included adults aged 18–65 years with radiographically confirmed knee osteoarthritis. Patients were assigned to one of two groups through a retrospective, non-randomized process based on the actual treatment received during their clinical follow-up. Group T received intra-articular adipose-derived stromal vascular fraction (SVF) injections, while Group C received conservative treatment with non-steroidal anti-inflammatory drugs (NSAIDs) only. SVF was obtained from abdominal adipose tissue using a standardized closed-system device and injected intra-articularly. Pain and functional outcomes were assessed using the Visual Analog Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline and at 1, 3, 6, 9, and 12 months. Results: Sixty-seven patients (41 SVF, 26 controls) were included, with comparable baseline characteristics (all p > 0.05). Preoperative VAS was lower in the SVF group (7.44 ± 1.44 vs. 8.31 ± 1.09; p = 0.029). At 12 months, VAS significantly decreased to 3.77 ± 1.49 in the SVF group, whereas it increased to 8.85 ± 0.67 in controls (p < 0.001). Similarly, baseline WOMAC scores were lower in the SVF group (62.6 ± 21.7 vs. 76.8 ± 8.76; p = 0.004). At 12 months, WOMAC improved to 29.4 ± 15 in the SVF group but worsened to 87.6 ± 3.21 in controls (p < 0.001). Within-group improvements were significant only in the SVF group (p < 0.001). No procedure-related complications were observed. Conclusions: The autologous adipose-derived stromal vascular fraction is an effective treatment option for early-stage KOA patients. However, a prospective, randomized, controlled study is warranted. Full article

Most high-tech drugs and tissue engineering products based on human chondrocytes currently available on the market are aimed at restoring traumatic damage to cartilage tissue. However, in the presence of inflammation, their regenerative potential is significantly reduced, which limits their use in patients with osteoarthritis—one of the most common degenerative and inflammatory joint pathologies. The central element of the pathogenesis of osteoarthritis is inflammation—not classical acute inflammation, but rather chronic low-grade inflammation, primarily mediated by mechanisms of the innate immune response. Therefore, a key challenge is to enhance the anti-inflammatory effectiveness of cell-based drugs to broaden their indications to include degenerative diseases such as osteoarthritis and arthrosis. In recent years, cell-based drugs using stem cells, including mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs), and stromal vascular fraction (SVF) cells, have been actively studied. Despite their confirmed safety in inflammatory processes, meta-analyses of clinical trials show limited effectiveness in improving symptoms and MRI data in the treatment of osteoarthritis. A promising direction appears to be the development of combined cell-based drugs that combine MSCs with M2-polarized macrophages; however, data on their clinical effectiveness are still insufficient. This review explores key cellular effectors of inflammation and its molecular mechanisms, potential strategies for creating tissue engineering products that possess not only regenerative but also pronounced anti-inflammatory effects. The development of such products will expand their application in the treatment of inflammatory-degenerative joint diseases. Full article

Background/Objectives: Knee osteoarthritis (OA) is a common degenerative joint disease for which conservative treatments often provide limited long-term benefit. Adipose-derived stromal cells delivered as stromal vascular fraction (SVF) represent a minimally invasive orthobiological approach with potential anti-inflammatory and regenerative effects. This study aimed to evaluate the clinical effectiveness and safety of intra-articular autologous SVF therapy and to explore patient- and treatment-related factors influencing outcomes over one year. Methods: This single-center retrospective study included 48 patients with knee OA Kellgren–Lawrence (KL) grade II–III treated with a single intra-articular injection of autologous SVF between June 2020 and February 2022. Clinical outcomes were assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS) at baseline and at 3 and 12 months post-treatment. Associations between clinical outcomes and age, sex, body mass index (BMI), OA grade, and administered cell dose were analyzed. Results: Significant improvements were observed in all KOOS domains at 3 months post-treatment (p < 0.001). At 12 months, improvements remained significant across domains, although Symptom scores showed slight attenuation. Higher administered cell dose was associated with greater improvement in KOOS Quality of Life (CFU-F indicators, r_s = 0.41–0.45, p < 0.01) and Sport and Recreation (TNC indicators, r_s = 0.36–0.38, p < 0.05) at 12 months, while younger age predicted greater QoL improvement and normal BMI was associated with better Symptom outcomes. Radiographic OA severity did not significantly influence treatment response, and sex-related differences were minimal. No serious adverse events were recorded. Discussion: SVF therapy was associated with sustained functional improvement and demonstrated a favorable safety profile in patients with moderate knee OA. Although demographic and treatment-related factors showed limited influence, cell dose, BMI, and age may affect selected outcomes. Prospective controlled studies with larger cohorts and longer follow-up are required to optimize patient selection and treatment protocols. Conclusions: These findings suggest that autologous SVF therapy may represent a safe and effective complementary treatment option for patients with moderate knee osteoarthritis seeking alternatives to more invasive interventions; however, these results should be confirmed in prospective controlled studies. Full article

Stromal vascular fraction (SVF) has emerged as a versatile autologous therapeutic strategy across multiple regenerative medicine applications. Derived from adipose tissue, SVF exerts its effects primarily through paracrine, immunomodulatory, pro-angiogenic, and anti-fibrotic mechanisms rather than direct cell differentiation. Potential regenerative outcomes have been reported in bone, cartilage, scar modulation, and neural repair, highlighting a shared pro-regenerative cascade centered on early inflammation control and vascular support. Indeed, increasing evidence suggests that synergy with biomaterials and point-of-care one-step approaches further enhances SVF efficacy. Regarding the real clinical potential, however, transability is still limited due to heterogeneity in isolation methods, lack of standardization, and insufficient large-scale randomized controlled trials. Full article

Background: Perivascular adipose tissue (PVAT) contains adipocytes and a stromal-vascular fraction with immune cells that modulate the adjacent vasculature. The presence of immune cells in PVAT of vascular beds is poorly understood—are they resident or recruited? We propose a novel resident microbiome present in PVAT, given the immune-rich stromal environment. Hypothesis: We hypothesized the existence of distinct bacterial and viral communities in healthy PVAT compared to non-PVAT adipose tissues. Methods: PVAT samples from thoracic and abdominal aorta, mesenteric resistance arteries, non-PVAT tissues (subscapular brown adipose tissue, retroperitoneal white adipose tissue), and fecal samples were collected one year apart from male Dahl SS rats, split into two cohorts (2023 and 2024, n = 3 each). Whole-genome shotgun sequencing (CosmosID) and 16S rRNA gene analysis assessed microbial relative abundance. Results: PVAT harbored bacterial and viral sequences, and species composition varied significantly between cohorts. Bacterial and viral fecal samples showed lower variability. Conclusions: PVAT microbiome differed dramatically from the fecal microbiome, with temporal influences on bacterial and viral diversity, marking the first such report. Despite inherent limitations, these findings establish the potential of PVAT microbiota in vascular biology and immune modulation, paving the development of microbiome-targeted drugs to address vascular dysfunctions. Full article

Background: Autologous fat grafting is widely used in reconstructive, aesthetic and regenerative surgery and often requires repeated applications. Cryopreservation of lipoaspirate enables autologous fat banking and off-the-shelf availability; however, its clinical implementation is limited by freezing-induced tissue injury, regulatory requirements and uncertainties regarding the optimal preservation protocol. Glycerol is a biocompatible cryoprotective agent with promising preliminary data. Nevertheless, the optimal concentration for lipoaspirate cryopreservation remains unknown. The aim of this study was to determine the optimal glycerol concentration for preservation of adipose tissue processed according to the Cell-Enriched Lipotransfer (CELT) protocol in clinically relevant volumes under GMP-compatible conditions. Methods: Lipoaspirates from 10 patients were processed by centrifugation according to the CELT protocol and allocated into experimental groups: fresh unfrozen control, frozen samples without cryoprotectant, frozen samples with PBS, and frozen samples supplemented with glycerol in concentrations ranging from 10% to 60%. Samples were cryopreserved using a controlled freezing rate at a temperature of −80 °C for 24 h. Large-volume cryopreservation was additionally performed with the best concentration of glycerol. Post-thaw tissue quality was assessed by resazurin assay of whole tissue, stromal vascular fraction (SVF) cell live/dead counting, and resazurin assay after short-term cell culture. Results: Glycerol supplementation improved post-thaw tissue viability compared with cryopreservation without cryoprotectant or with PBS alone. An optimal concentration range between 10% and 30% glycerol was identified, with highest preservation of metabolic activity and surviving cell yield observed at 20%. Higher glycerol concentrations resulted in a marked decline in tissue quality. Cryopreservation in large volume was feasible and did not impair post-thaw viability compared with small-volume samples. Conclusions: Glycerol-based cryopreservation allows effective and GMP-compatible preservation of human lipoaspirate. An optimal glycerol concentration range was identified, enabling large-volume fat banking without compromising tissue quality. This protocol provides a clinically applicable strategy for autologous fat storage and may facilitate repeated reconstructive and regenerative treatments. Full article

Myeloid differentiation factor 88 (MyD88) signaling plays a central role in inflammatory pathway activation. Adipose-derived interleukin-10 (IL-10), which is induced by insulin and lipopolysaccharides, suppresses hepatic glucose production. This study investigated the role of MyD88/IL-10 signaling in diabetes-induced systemic inflammation and hepatic gluconeogenesis. Stromal vascular fractions (SVFs) were isolated from the adipose tissue of Lepr^db/db and Lepr^db/dbMyD88^−/− mice and treated with IL-10 followed by analysis of inflammatory cytokine expression. IL-10 (10 or 50 ng) was injected into adipose tissue of type 2 DM (T2DM) (Lepr^db/db) mice to investigate its effect on blood dipeptidyl peptidase-4 (DPP4) activity, insulin resistance, and hepatic gluconeogenic signaling. Hepatic inflammatory markers, gluconeogenic gene expression, and metabolic parameters were assessed. Compared with wild-type mice, Lepr^db/db mice exhibited significantly reduced FOXP3 protein expression and IL-10 levels in adipose tissue, accompanied by increased blood DPP4 activity and adiponectin levels, elevated hepatic inflammatory cytokines, and increased G6pc and Pck1 mRNA expression. In contrast, Lepr^db/dbMyD88^−/− mice showed increased Foxp3 protein and PDGFα mRNA expression, decreased IL-6 and CCL2 mRNA expression in SVFs, increased IL-10 levels in adipose tissue, and lower blood adiponectin and ALT levels. MyD88 deletion also attenuated Kupffer cell accumulation, hepatic inflammatory cytokine expression, and gluconeogenic gene expression. In vitro, IL-10 treatment of SVFs from Lepr^db/db mice significantly reduced IL-6 and CCL2 expression and increased Foxp3 mRNA expression. In vivo, adipose IL-10 injection increased Foxp3 and IL-10 expression, expanded Treg cells in SVFs, and activated hepatic Akt signaling, while suppressing pJNK and pNF-κB signaling. These changes were accompanied by reduced blood DPP4 activity, ALT and adiponectin levels, decreased Kupffer cell-derived inflammatory cytokines, reduced hepatic G6pc and Pck1 expression, and improved glucose tolerance. MyD88 signaling induces adipose IL-6 and CCL2, liver inflammation and gluconeogenesis, and blood DPP4 activity by reducing IL-10 and Foxp3 of adipose tissue in T2DM. Enhancing adipose IL-10 induces Treg expansion, inhibits JNK and NF-κB signaling, and alleviates hepatic gluconeogenesis and insulin resistance. MyD88 inhibition or IL-10 elevation in adipose tissue may represent a novel strategy for metabolic syndrome. Full article

Intracerebral hemorrhage (ICH) remains a devastating condition with no available therapies that can effectively mitigate secondary injury and promote neurological repair. This research presents a novel combinatorial regenerative strategy, concurrently delivering adipose-derived stromal vascular fraction (SVF) within an adhesive self-assembling peptide (HGF-RADA16-IKVAV) nanohydrogel (HGF). In a clinically relevant rat model of ICH with hematoma evacuation, the combined therapy of HGF and SVF demonstrated synergistic and enhanced efficacy. In the short term, the combined therapy demonstrated hemostatic benefits, and significantly reduced hematoma volume, brain edema, neuronal apoptosis and neuroinflammation indicated by pro-inflammatory markers (NLRP3, caspase-1, Iba-1, CD68, GFAP) while increasing the levels of anti-inflammatory (CD206) and angiogenic (CD31) markers. Longitudinal behavioral assessments conducted over six weeks demonstrated persistent and significant improvements in motor coordination, forelimb strength, and gait parameters within the HGF + SVF group, surpassing all monotherapies. Ultrastructural analysis also showed that myelinated axons were better preserved at the injury border, with thicker myelin sheaths. These findings demonstrate that the co-administration of SVF with an adhesive and hemostatic hydrogel collaboratively diminishes secondary injury, modulates neuroinflammation, and promotes functional and structural brain recovery following ICH, indicating a promising and translatable strategy. Full article

Background/Objectives: Stromal vascular fraction (SVF) from adipose tissue contains regenerative cell populations, including adipose-derived stem cells (ADSCs), and is increasingly used in clinical therapies. However, the effects of isolation technique and donor characteristics on SVF yield and viability remain unclear. This study aims to assess the impact of mechanical versus enzymatic isolation, as well as donor age and sex, on SVF total nucleated cell count (TNC) and viability. Methods: A retrospective analysis was conducted on 114 patients undergoing ADSC harvesting via a mini-liposuction. SVF was isolated using enzymatic digestion (n = 100) or mechanical digestion (n = 14). Percent viability and TNC were assessed using the Chemometec NC-200 NucleoCounter^®. The influence of isolation technique, donor age, and donor sex on SVF yield and viability was evaluated using Pearson’s correlation and independent t-tests. Results: Enzymatic digestion yielded significantly higher cell viability compared to mechanical isolation (p < 0.001), although no significant difference in TNC was observed between the two methods. Increasing donor age was modestly associated with reduced viability in enzymatically processed samples but not in mechanically processed samples. Donor age showed no significant association with TNC for either isolation method. Donor sex was not correlated with viability in either group; however, female donors exhibited significantly higher TNC following enzymatic digestion, a trend not observed with mechanical isolation. Conclusions: Enzymatic digestion preserves cell viability more effectively than mechanical methods, while donor age and sex have variable effects depending on the isolation protocol. These findings underscore the importance of considering both biological and methodological factors in SVF preparation for clinical use. Further studies with larger, balanced cohorts are needed to validate these results. Full article

Skin aging, photoaging, and chronic wounds are increasingly recognized to be driven by mitochondria-centered mechanisms characterized by oxidative stress, defective mitophagy, and impaired bioenergetics in cutaneous cells. Autologous biologics, including platelet-rich plasma, stromal vascular fraction, bone marrow aspirate concentrate, and mesenchymal stromal/stem cell–derived products, are widely used for skin rejuvenation and wound repair. Recent studies have suggested that many of these effects are mediated by mitochondrial mechanisms, including metabolic reprogramming, redox modulation, and intercellular mitochondrial transfer. Concurrently, biophysical modalities such as red/near-infrared photobiomodulation (PBM), low-intensity pulsed ultrasound, mechanical stimulation, and nanoengineered cues can modulate mitochondrial function in skin-relevant cells. In this review, we integrate these lines of evidence to introduce the concept of mitochondria-targeted biophysical priming of autologous biologics for dermatological applications. We summarize the mitochondrial biology in skin pathology, evaluate these biologics as mitochondria-active therapies, and outline ex vivo priming implementation using PBM, ultrasound, or mechanical stimulation. Finally, we discuss key regulatory considerations that support clinical translation. Full article

Background and Objectives: Intra-articular injection of adipose-derived stromal vascular fraction (SVF) has emerged as a promising regenerative treatment for knee osteoarthritis (OA) because of its heterogeneous cellular composition and potent anti-inflammatory paracrine effects. Although SVF therapy has demonstrated clinical efficacy, the timing of pain relief and the influence of SVF cell dose on early clinical outcomes remain incompletely defined. Materials and Methods: This retrospective study included 146 patients (217 knees) with Kellgren–Lawrence (K–L) grade II–IV knee OA who underwent intra-articular injection of autologous adipose-derived SVF and completed a minimum follow-up of 1 year. Pain was assessed using the visual analog scale (VAS), and patients reported the time to perceived pain improvement after treatment. Radiographic severity was evaluated using the K–L grading system. Correlation analyses were performed to assess associations between pain-related outcomes, SVF cell number, and radiographic severity. Results: VAS scores improved significantly from baseline to the final follow-up (p < 0.01). Patients reported perceived pain improvement at a mean of 18.9 ± 14.5 days after SVF injection. The mean injected dose was 7.4 × 10⁷ total SVF cells per knee, including approximately 7.0 × 10⁶ stromal cells. Higher SVF cell numbers were significantly associated with greater pain improvement and lower VAS scores at final follow-up (p < 0.001 for both). Radiographic severity was not significantly correlated with pain at final follow-up, the magnitude of pain improvement, or the time to symptom relief. No clinically relevant adverse events were observed. Conclusions: Intra-articular injection of high-dose autologous SVF was associated with rapid and clinically meaningful pain relief, with symptom improvement occurring within approximately 3 weeks after treatment. The dose-dependent association and the lack of correlation with radiographic severity suggest that early pain relief is primarily mediated by the anti-inflammatory and paracrine effects of SVF rather than immediate structural cartilage regeneration. Full article

Adipose tissue includes various cell types beyond the typical adipocytes. The stromal vascular fraction (SVF) contains mesenchymal stem cells (MSCs), pericytes, and endothelial cells, which can be isolated from adipose tissue by mechanical and enzymatic methods. The composition of the SVF is heterogeneous, and donor factors such as sex, age, body mass index (BMI), and harvesting site are associated with variations in cellular composition and viability. The expression of specific surface markers, which determine the immunophenotype of the cells, can also vary. In this study, we investigated the effects of donor age, BMI, and harvesting site on cell yield, viability, and size. Our results showed that BMI significantly influenced cell yield and size, with overweight and obese donors yielding more cells than normal-weight donors. Additionally, cells isolated from the adipose tissue of the thighs/legs were larger than those from other areas. Flow cytometry showed considerable variability in SVF composition among donors. These results emphasize that SVF donor characteristics have a significant impact on cell yield, viability, and cell size, with the immunophenotype being highly donor-dependent. Understanding these factors is crucial for optimizing cell yield and defining populations for therapeutic applications of SVF cells. Full article

Background/Objectives: Itaconic acid (ITA) is an immunometabolite with anti-inflammatory and metabolic regulatory functions, but its cellular source and role in brown adipose tissue (BAT) remain unclear. This study aims to reveal the expression patterns of the key ITA synthesis gene Irg1 in BAT at different developmental stages and to investigate the effects of cold exposure and exogenous ITA on BAT metabolic function and cardioprotection. Methods: Single-cell RNA sequencing was used to analyze the gene expression profiles of stromal vascular fraction (SVF) cells in BAT from P7 neonatal and adult mice. Bioinformatic methods were applied to identify cell types expressing Irg1. Cold exposure (4 °C) and exogenous ITA treatment were employed to evaluate BAT morphology, and the ITA content in BAT was detected using gas chromatography–triple quadrupole mass spectrometry, UCP1 protein expression, and body temperature changes. A transverse aortic constriction (TAC) surgery model was established to induce cardiac dysfunction, and BAT excision was performed to explore the BAT-dependent effects of ITA on myocardial hypertrophy, fibrosis, and cardiac function. Results: In P7 neonatal mouse BAT, Irg1 was predominantly expressed in a subset of interferon-responsive activated macrophages (macrophage27), while in adult mice, it was mainly expressed in neutrophils and a functionally similar macrophage subset (macrophage25). Cold exposure significantly suppressed Irg1 expression in neutrophils but did not affect its expression in macrophages, also resulting in a significant decrease in ITA content in BAT. Exogenous ITA significantly enhanced BAT thermogenesis under cold conditions, which manifested as reduced lipid droplets, upregulated UCP1 expression, and increased body temperature. In the TAC model, ITA treatment markedly improved cardiac function, attenuated myocardial hypertrophy and fibrosis, and these protective effects were significantly diminished after BAT excision. Conclusions: ITA promotes cold adaptation and ameliorates cardiac injury by enhancing BAT metabolic function, and its effects depend on the presence of BAT. This study provides new insights for the treatment of metabolic cardiovascular diseases. Full article

Obesity-associated inflammation underlies much of cardiometabolic pathology, reflecting the convergence of chronic, low-grade systemic immune activation with region-specific maladaptation of adipose depots. Among these, epicardial adipose tissue (EAT)—a visceral fat layer contiguous with the myocardium and sharing its microvasculature—functions as a cardio-proximal immunometabolic interface that influences atrial fibrillation, heart failure with preserved ejection fraction, and coronary atherogenesis through paracrine crosstalk. These relationships extend beyond crude measures of adiposity, emphasizing the primacy of local inflammatory signaling, adipokine flux, and fibro-inflammatory remodeling at the EAT–myocardium interface. Of importance, substantial weight reduction only partially reverses obesity-imprinted transcriptional and epigenetic programs across subcutaneous, visceral, and epicardial depots, supporting the concept of an enduring adipose memory that sustains cardiovascular (CV) risk despite metabolic improvement. Accordingly, therapeutic strategies should move beyond weight-centric management toward mechanism-guided interventions. Resolution pharmacology—leveraging specialized pro-resolving mediators and their cognate G-protein-coupled receptors—offers a biologically plausible means to terminate inflammation and reprogram immune–stromal interactions within adipose and CV tissues. Although preclinical studies report favorable effects on vascular remodeling, myocardial injury, and arrhythmic vulnerability, clinical translation is constrained by pharmacokinetic liabilities of native mediators and by incomplete validation of biomarkers for target engagement. This review integrates mechanistic, depot-resolved, and therapeutic evidence to inform the design of next-generation anti-inflammatory strategies for obesity-related CV disease. Full article

Background/Objectives: Knee osteoarthritis (KOA) is a common pathology characterized by impaired joint cartilage. Mesenchymal stromal cell (MSC)-based treatments, such as stromal vascular fraction (SVF), are increasingly being used for their potential cartilage-generating capabilities; however, there is still insufficient evidence to confirm their effectiveness. The aim of the study was to assess the efficacy of SVF treatment in KOA in terms of pain relief. Methods: An experimental clinical trial was performed. We included adults with symptomatic KOA who attended Celular Clinic (Andorra). A laboratory-manufactured and standardized SVF product (Celstem^®) was applied to selected patients. Clinical, functional, and radiological assessments using the visual analog scale, KOOS (Knee Injury and Osteoarthritis Outcome Score), SF-36 scale, and MOCART classification (Magnetic Resonance Observation of Cartilage Repair Tissue) were performed. Variables were compared before treatment and at one, six, and twelve months after treatment. Adverse effects were reported. Results: In total, 184 patients were included in the clinical trial, 78 of whom were finally analyzed. There were statistically significant differences in both resting and activity-related pain and in all KOOS subscales after SVF treatment (p < 0.001). The quality of life also showed significant changes (p = 0.021). No significant changes were observed in MOCART values. However, a positive association was found between MOCART and cell yield. Few adverse effects were reported. Conclusions: Our nonrandomized uncontrolled clinical trial showed that SVF treatment has promise to reduce pain in patients with KOA. Improvements in functionality and quality of life were also observed. Future randomized controlled trials regarding SVF versus placebo therapies will further clarify this potential. Full article