Industry updates from the field of stem cell research and regenerative medicine in December 2024.

Latest developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from non-academic institutions in December 2024.

Programming of synthetic regulatory DNA for cell-type targeting in humans.

In a recent study in Nature, Gosai et al. introduce a framework to engineer and validate synthetic DNA regulatory elements showing cell-type-specific activity in human cell lines, closing the distance to the machine-driven design of functional regulatory sequences with therapeutic applications in humans.

Current and novel biomarkers in cardiogenic shock.

Cardiogenic shock (CS) carries a 30-50% in-hospital mortality rate, with little improvement in outcomes in the last decade. Challenges in improving outcomes are closely linked to the frequent late presentation or diagnosis of CS where the 'point of no return' has often passed, leading to haemodynamic dysregulation, progressive myocardial depression, hypotension, and a downward spiral of hypoperfusion, organ dysfunction and decreasing myocardial function, driven by inflammation and metabolic derangements. Novel therapeutic interventions may have varying efficacy depending on the type and stage of shock in which they are applied.

Compact and cGMP-compliant automated synthesis of [F]FSPG on the Trasis AllinOne™.

Background: (S)-4-(3-F-Fluoropropyl)-ʟ-glutamic acid ([F]FSPG) is a positron emission tomography radiotracer used to image system x, an antiporter that is upregulated in several cancers. Not only does imaging system x with [F]FSPG identify tumours, but it can also provide an early readout of response and resistance to therapy. Unfortunately, the clinical production of [F]FSPG has been hampered by a lack of robust, cGMP-compliant methods.

Treatment of Venous Thromboembolism with Edoxaban over 18 Months: Results from ETNA-VTE Europe.

Background:  The benefits and risks of extending anticoagulant treatment beyond the first 3 to 6 months in patients with venous thromboembolism (VTE) in clinical practice are not well understood.

Methods:  ETNA-VTE Europe is a prospective, noninterventional, post-authorization study in unselected patients with VTE treated with edoxaban in eight European countries for up to 18 months. Recurrent VTE, major bleeding, and all-cause death were the primary study outcomes.

Personalized Dynamic Prediction Model for Biopsy Timing in Patients With Prostate Cancer During Active Surveillance.

Importance: Active surveillance (AS) for patients with prostate cancer (PC) often includes fixed repeat prostate biopsies that do not account for the varying risk of reclassification to significant disease. Given the invasive nature and potential complications of biopsies, a personalized approach is needed to balance the burden of biopsies with the risk of missing disease progression.

Objective: To develop and externally validate a dynamic model that predicts an individual's risk of PC reclassification during AS.

Influence of Worsening Renal Function and Baseline Chronic Kidney Disease on Clinical Outcomes in Patients With Chronic Coronary Syndromes: Insights From the REAL-CAD Study.

Background: The effect of worsening renal function and baseline chronic kidney disease (CKD) on outcomes in patients with chronic coronary syndrome in the setting of optimal medical therapy remains unknown.

Methods And Results: The REAL-CAD (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease) study is a prospective, multicenter, randomized trial of high-dose (pitavastatin 4 mg/day) or low-dose (pitavastatin 1 mg/day) statin therapy in 12 118 patients with chronic coronary syndrome. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, or unstable angina requiring hospitalization (major adverse cardiac and cerebral events [MACCE]).

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT.

Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsing forms of multiple sclerosis (MS) that are refractory to disease-modifying therapy (DMT). AHSCT after failure of high-efficacy DMT in aggressive forms of relapsing-remitting MS is a generally accepted indication, yet the optimal placement of this approach in the treatment sequence is not universally agreed upon. Uncertainties also remain with respect to other indications, such as in rapidly evolving, severe, treatment-naive MS, progressive MS, and neuromyelitis optica spectrum disorder (NMOSD).

Assessment of the thymus in fetuses prior to spontaneous preterm birth using functional MRI.

Objectives: The aim of this study was to utilise T2* relaxometry (an indirect method of quantifying tissue oxygenation) to assess the fetal thymus in uncomplicated pregnancies throughout gestation and in a cohort of fetuses that subsequently deliver very preterm.

Methods: A control group of participants with low-risk pregnancies were recruited and retrospectively excluded if they developed any pregnancy related complications after scanning. Participants were recruited who were deemed to be at very high risk of delivery prior to 32 weeks' gestation and retrospectively excluded if they did not deliver prior to this gestation.

Macrophage to neuron communication via extracellular vesicles in neuropathic pain conditions.

Neuropathic pain following peripheral nerve injury results from maladaptive changes in neurons and immune cells contribution to mechanisms underlying chronic pain. Specifically, in dorsal root ganglia (DRG), sensory neuron cell bodies release extracellular vesicles (EVs) which promote pro-inflammatory macrophage accumulation that facilitates nociceptive signalling. Here, we show that macrophages shuttle EVs to neurons.

Iron management and exercise training in individuals with chronic kidney disease: lived experiences.

Background: Non-anaemic iron deficiency is highly prevalent in people living with chronic kidney disease (CKD) but is underdiagnosed and undertreated, especially in earlier stages of CKD. A multicentre trial assessing the effect of intravenous iron supplementation in iron-deficiency but not anaemic people with CKD included a qualitative sub-study that aimed to explore the patient experience and psychosocial impact of living with CKD and iron deficiency, and the experience of the therapeutic intervention (intravenous iron and exercise).

Methods: Semi-structured interviews were conducted with 23 trial participants blinded to treatment.

Blood absolute lymphocyte count and trajectory are important in understanding severe COVID-19.

Background: Low blood absolute lymphocyte count (ALC) may predict severe COVID-19 outcomes. Knowledge gaps remain regarding the relationship of ALC trajectory with clinical outcomes and factors associated with lymphopenia.

Methods: Our post hoc analysis of the Therapeutics for Inpatients with COVID-19 platform trial utilized proportional hazards models to assess relationships between Day (D) 0 lymphopenia (ALC < 0.

Clinicians' perspectives on the use of artificial intelligence to triage MRI brain scans.

Artificial intelligence (AI) tools can triage radiology scans to streamline the patient pathway and also relieve clinician workload. Validated AI tools can mitigate the delays in reporting scans by flagging time-sensitive and actionable findings. In this study, we aim to investigate current stakeholder perspectives and identify obstacles to integrating AI in clinical pathways.

Low-cost male urogenital simulator for penile implant surgery training: a 3D printing approach.

Background: Penile implant surgery is the standard surgical treatment for end-stage erectile dysfunction. However, the growing complexity of modern high-tech penile prostheses has increased the demand for more practical training opportunities. The most advanced contemporary training methods involve simulation training using cadavers, with costs exceeding $5,000 per cadaver, inclusive of biohazard fees.

Evaluation of Intestinal Permeability Using Serum Biomarkers in Learning Early About Peanut Allergy Trial.

Background: Intestinal barrier dysfunction may lead to a break in tolerance and development of food allergy (FA). There is contradictory evidence on whether intestinal permeability (IP) is altered in IgE-mediated FA. Thus, we sought to determine whether IP differed between children with eczema who did (FA group) or did not (atopic controls, ACs) develop FA and whether peanut sensitization, allergy, and early introduction impacted IP using serum biomarkers zonulin, soluble CD14, and Intestinal Fatty Acid Binding Protein among randomly selected participants enrolled in the Learning Early About Peanut allergy trial.

An Overview of Patient-reported Outcomes for Men with Prostate Cancer: Results from the PIONEER Consortium.

Background And Objective: Patient-reported outcome measures (PROMs) are increasingly being used to capture the patients' perspective of their functional status and quality of life (QoL). Big data can help us better understand patient-reported outcomes (PROs). Using prospectively collected data from the Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe (PIONEER) consortium, we aimed to describe the functional status and QoL in men with prostate cancer (PCa) treated with active surveillance (AS), radical prostatectomy (RP), and radiotherapy (RT), and to demonstrate the applicability of PROM data on a large scale and at a European level.

Conquering Overtreatment of DCIS: Lessons from PRECISION.

As we cannot reliably distinguish indolent, low-risk ductal carcinoma in situ (DCIS) from potentially progressive, high-risk DCIS, all women with DCIS diagnosis undergo intensive treatment without any benefit. The PREvent ductal Carcinoma In Situ Invasive Overtreatment Now team was established to unravel DCIS biology and develop new multidisciplinary approaches for accurate risk stratification to tackle the global problem of DCIS overdiagnosis and overtreatment. See related article by Bressan et al.

Symptom Evolution in Individuals with Ongoing Symptomatic COVID-19 and Post COVID-19 Syndrome After SARS-CoV-2 Vaccination Versus Influenza Vaccination.

Background: COVID-19 symptoms may persist beyond acute SARS-CoV-2 infection, as ongoing symptomatic COVID-19 [OSC] (symptom duration 4-12 weeks) and post-COVID syndrome [PCS] (symptom duration ≥12 weeks). Vaccination against SARS-CoV-2 decreases OSC/PCS in individuals subsequently infected with SARS-CoV-2 post-vaccination. Whether vaccination against SARS-CoV-2, or any other vaccinations (such as against influenza) affects symptoms in individuals already experiencing OSC/PCS, more than natural symptom evolution, is unknown.

Whole examination AI estimation of fetal biometrics from 20-week ultrasound scans.

The current approach to fetal anomaly screening is based on biometric measurements derived from individually selected ultrasound images. In this paper, we introduce a paradigm shift that attains human-level performance in biometric measurement by aggregating automatically extracted biometrics from every frame across an entire scan, with no need for operator intervention. We use a neural network to classify each frame of an ultrasound video recording.

Single-cell RNA-seq identifies protracted mouse germline X chromosome reactivation dynamics directed by a PRC2-dependent mechanism.

Female primordial germ cells (PGCs) undergo X chromosome reactivation (XCR) during genome-wide reprogramming. XCR kinetics and dynamics are poorly understood at a molecular level. Here, we apply single-cell RNA sequencing and chromatin profiling on germ cells from F mouse embryos, performing a precise appraisal of XCR spanning from migratory-stage PGCs to gonadal germ cells.