Alcyomics (United Kingdom)

Adipose tissue is an abundant and clinically accessible source of stromal cells. Stromal vascular fraction (SVF) and nanofat have been widely investigated for their regenerative potential; however, commercial systems vary considerably in yield, viability, and regulatory oversight. Most devices report fresh results only, with limited validation following cryopreservation. Mesenchymal stromal cells derived from adipose tissue have also attracted attention due to their accessibility, immunomodulatory effects, and multipotent differentiation capacity. Uvence has developed a proprietary workflow for adipose tissue processing that integrates washing, cryopreservation, thawing, and emulsification within a Human Tissue Authority-regulated laboratory. The process includes Good Manufacturing Practices (GMP) Annex 1-aligned environmental monitoring and independent quality control (QC) testing. Critically, this workflow validates postthaw cell viability, addressing a gap in current SVF/nanofat approaches. Three cryopreserved donor samples demonstrated a mean postthaw viability of ∼91% (range 90.5-92%), consistently exceeding the International Federation for Adipose Therapeutics and Science (IFATS)/ International Society for Cell and Gene Therapy (ISCT) 70% threshold. Benchmarking against global systems showed Uvence postthaw viability to be equivalent to or higher than fresh outcomes reported for enzymatic platforms (Celution, 85-91%; InGeneron, 86%) and mechanical platforms (Lipocube, Tulip, ∼96%). Unlike competitor devices, Uvence has validated freeze-thaw performance, providing a stable and compliant platform. This study also presents in vitro culture and characterization of stromal cells expanded from Uvence nanofat-derived SVF samples, including flow cytometry, morphology, and trilineage differentiation. Flow cytometry confirmed high expression of CD73, CD90, and CD105, with minimal expression of CD34/CD45, consistent with the ISCT criteria. While these findings are limited to research characterization and do not constitute approval for therapeutic use, they demonstrate that the Uvence workflow delivers a quality-focused approach to adipose tissue processing.

Abstract Anti-senescence interventions are exceptionally effective in alleviating a wide range of age-associated diseases and disabilities. However, the sensitivity and specificity of current senolytic interventions are limited. Mitochondrial dysfunction is an integral part of the senescent phenotype and we demonstrate that specific loss of complex I-linked coupled respiration and the inability to maintain mitochondrial membrane potential upon respiratory stimulation are early and persistent features in a cell’s progression towards senescence.We thus identify senescence-associated mitochondrial dysfunction as a targetable vulnerability of senescent cells and show that further decreasing mitochondrial membrane potential of senescent cells with a low concentration of a mitochondrial uncoupler synergistically enhances thein vitrosenolytic efficacy of BH3 mimetic drugs, including Navitoclax, by up two orders of magnitude.Moreover, in anin vivomouse model of radiation-induced premature ageing, we show that a short-term intervention combining the mitochondrial uncoupler BAM15 with Navitoclax at a dose two orders of magnitude lower than typically used reduces frailty and improves cognitive function for at least 8 months after irradiation. Therefore our study shows that compromised mitochondrial functional capacity is a specific vulnerability of senescent cells which can be targeted by mild uncouplingin vitroandin vivo.

ObjectivesThe Delta Study was undertaken to improve the diagnosis of mood disorders in individuals presenting with low mood. The current study aimed to estimate the prevalence and explore the characteristics of mood disorders in participants of the Delta Study, and discuss their implications for clinical practice.MethodsIndividuals with low mood (Patients Health Questionnaire‐9 score ≥5) and either no previous mood disorder diagnosis (baseline low mood group, n = 429), a recent (≤5 years) clinical diagnosis of MDD (baseline MDD group, n = 441) or a previous clinical diagnosis of BD (established BD group, n = 54), were recruited online. Self‐reported demographic and clinical data were collected through an extensive online mental health questionnaire and mood disorder diagnoses were determined with the World Health Organization Composite International Diagnostic Interview (CIDI).ResultsThe prevalence of BD and MDD in the baseline low mood group was 24% and 36%, respectively. The prevalence of BD among individuals with a recent diagnosis of MDD was 31%. Participants with BD in both baseline low mood and baseline MDD groups were characterized by a younger age at onset of the first low mood episode, more severe depressive symptoms and lower wellbeing, relative to the MDD or low mood groups. Approximately half the individuals with BD diagnosed as MDD (49%) had experienced (hypo)manic symptoms prior to being diagnosed with MDD.ConclusionsThe current results confirm high under‐ and misdiagnosis rates of mood disorders in individuals presenting with low mood, potentially leading to worsening of symptoms and decreased well‐being, and indicate the need for improved mental health triage in primary care.

Sensitization to chemicals resulting in an allergy is an important health issue. The current gold-standard method for identification and characterization of skin-sensitizing chemicals was the mouse local lymph node assay (LLNA). However, for a number of reasons there has been an increasing imperative to develop alternative approaches to hazard identification that do not require the use of animals. Here we describe a human in-vitro skin explant test for identification of sensitization hazards and the assessment of relative skin sensitizing potency. This method measures histological damage in human skin as a readout of the immune response induced by the test material. Using this approach we have measured responses to 44 chemicals including skin sensitizers, pre/pro-haptens, respiratory sensitizers, non-sensitizing chemicals (including skin-irritants) and previously misclassified compounds. Based on comparisons with the LLNA, the skin explant test gave 95% specificity, 95% sensitivity, 95% concordance with a correlation coefficient of 0.9. The same specificity and sensitivity were achieved for comparison of results with published human sensitization data with a correlation coefficient of 0.91. The test also successfully identified nickel sulphate as a human skin sensitizer, which was misclassified as negative in the LLNA. In addition, sensitizers and non-sensitizers identified as positive or negative by the skin explant test have induced high/low T cell proliferation and IFNγ production, respectively. Collectively, the data suggests the human in-vitro skin explant test could provide the basis for a novel approach for characterization of the sensitizing activity as a first step in the risk assessment process.