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Use of cell-based medicinal products (CBMPs) represents a state-of-the-art approach for reducing general immunosuppression in organ transplantation. We tested multiple regulatory CBMPs in kidney transplant trials to establish the safety of regulatory CBMPs when combined with reduced immunosuppressive treatment. The ONE Study consisted of seven investigator-led, single-arm trials done internationally at eight hospitals in France, Germany, Italy, the UK, and the USA (60 week follow-up). Included patients were living-donor kidney transplant recipients aged 18 years and older. The reference group trial (RGT) was a standard-of-care group given basiliximab, tapered steroids, mycophenolate mofetil, and tacrolimus. Six non-randomised phase 1/2A cell therapy group (CTG) trials were pooled and analysed, in which patients received one of six CBMPs containing regulatory T cells, dendritic cells, or macrophages; patient selection and immunosuppression mirrored the RGT, except basiliximab induction was substituted with CBMPs and mycophenolate mofetil tapering was allowed. None of the trials were randomised and none of the individuals involved were masked. The primary endpoint was biopsy-confirmed acute rejection (BCAR) within 60 weeks after transplantation; adverse event coding was centralised. The RTG and CTG trials are registered with ClinicalTrials.gov, NCT01656135, NCT02252055, NCT02085629, NCT02244801, NCT02371434, NCT02129881, and NCT02091232. The seven trials took place between Dec 11, 2012, and Nov 14, 2018. Of 782 patients assessed for eligibility, 130 (17%) patients were enrolled and 104 were treated and included in the analysis. The 66 patients who were treated in the RGT were 73% male and had a median age of 47 years. The 38 patients who were treated across six CTG trials were 71% male and had a median age of 45 years. Standard-of-care immunosuppression in the recipients in the RGT resulted in a 12% BCAR rate (expected range 3·2–18·0). The overall BCAR rate for the six parallel CTG trials was 16%. 15 (40%) patients given CBMPs were successfully weaned from mycophenolate mofetil and maintained on tacrolimus monotherapy. Combined adverse event data and BCAR episodes from all six CTG trials revealed no safety concerns when compared with the RGT. Fewer episodes of infections were registered in CTG trials versus the RGT. Regulatory cell therapy is achievable and safe in living-donor kidney transplant recipients, and is associated with fewer infectious complications, but similar rejection rates in the first year. Therefore, immune cell therapy is a potentially useful therapeutic approach in recipients of kidney transplant to minimise the burden of general immunosuppression. The 7th EU Framework Programme.

Study design: Randomized controlled trial with single-blinded primary outcome assessment. Objectives: To determine the efficacy and safety of autologous incubated macrophage treatment for improving neurological outcome in patients with acute, complete spinal cord injury (SCI). Setting: Six SCI treatment centers in the United States and Israel. Methods: Participants with traumatic complete SCI between C5 motor and T11 neurological levels who could receive macrophage therapy within 14 days of injury were randomly assigned in a 2:1 ratio to the treatment (autologous incubated macrophages) or control (standard of care) groups. Treatment group participants underwent macrophage injection into the caudal boundary of the SCI. The primary outcome measure was American Spinal Injury Association (ASIA) Impairment Scale (AIS) A–B or better at ⩾6 months. Safety was assessed by analysis of adverse events (AEs). Results: Of 43 participants (26 treatment, 17 control) having sufficient data for efficacy analysis, AIS A to B or better conversion was experienced by 7 treatment and 10 control participants; AIS A to C conversion was experienced by 2 treatment and 2 control participants. The primary outcome analysis for subjects with at least 6 months follow-up showed a trend favoring the control group that did not achieve statistical significance ( P =0.053). The mean number of AEs reported per participant was not significantly different between the groups ( P =0.942). Conclusion: The analysis failed to show a significant difference in primary outcome between the two groups. The study results do not support treatment of acute complete SCI with autologous incubated macrophage therapy as specified in this protocol.

Cell therapies offer the promise of treating and altering the course of diseases which cannot be addressed adequately by existing pharmaceuticals. Cell therapies are a diverse group across cell types and therapeutic indications and have been an active area of research for many years but are now strongly emerging through translation and towards successful commercial development and patient access. In this article, we present a description of a classification of cell therapies on the basis of their underlying technologies rather than the more commonly used classification by cell type because the regulatory path and manufacturing solutions are often similar within a technology area due to the nature of the methods used. We analyse the progress of new cell therapies towards clinical translation, examine how they are addressing the clinical, regulatory, manufacturing and reimbursement requirements, describe some of the remaining challenges and provide perspectives on how the field may progress for the future.

Cell and gene therapies (CGTs) are transforming medicine by offering potential cures for diseases previously considered untreatable. Despite rapid advancements, challenges remain in optimizing efficacy and safety and ensuring patient accessibility and preference due to high costs and clinical uncertainties, particularly for rare diseases and one‐time administration. The American Society of Clinical Pharmacology & Therapeutics (ASCPT) held a CGT satellite conference in 2025, titled “Cell and Gene Therapy: Transforming Treatment Paradigms for Patient‐Centric Care.” This manuscript summarizes the conference, covering gene therapies and T‐cell immunotherapies from scientific, clinical, and patient‐centered perspectives. Key topics on gene therapy included “platformization” to streamline development, lessons from adeno‐associated virus‐based gene therapies for hemophilia from patient and clinical perspectives, clinical pharmacology, and model‐informed drug development (MIDD) considerations. The conference also highlighted T‐cell immunotherapies including chimeric antigen receptor T therapy (CAR T), focusing on factors affecting cellular kinetics, efficacy, and safety, as well as emerging allogeneic CAR T for autoimmune diseases and MIDD strategies to optimize therapy design and clinical outcomes.

Ixmyelocel-T is an expanded, multicellular therapy produced from a patient's own bone marrow by selectively expanding two key types of bone marrow mononuclear cells: CD90+ mesenchymal stem cells and CD45+ CD14+ auto-fluorescent+ activated macrophages. Early phase clinical trials suggest that intramyocardial delivery of ixmyelocel-T might improve clinical, functional, symptomatic, and quality-of-life outcomes in patients with heart failure due to ischaemic dilated cardiomyopathy. We aimed to assess the safety and efficacy of catheter-based transendocardial injection of ixmyelocel-T cell therapy in patients with heart failure and reduced ejection fractions. In this randomised, double-blind, placebo-controlled phase 2B trial (ixCELL-DCM), patients from 31 sites in North America with New York Heart Association class III or IV symptomatic heart failure due to ischaemic dilated cardiomyopathy, who had left ventricular ejection fraction 35% or less, an automatic implantable cardioverter defibrillator, and who were ineligible for revascularisation procedures were randomly assigned (1:1) to receive ixmyelocel-T or placebo at the time of bone marrow aspiration and followed for 12 months. Randomisation was done through an interactive (voice/web) response system. The pharmacist, treating physician, and coordinator at each site were unblinded, but the the follow-up team was completely blinded. The primary endpoint was a composite of all-cause death, cardiovascular admission to hospital, and unplanned clinic visits to treat acute decompensated heart failure based on the blinded adjudication of an independent clinical endpoint committee. Primary efficacy endpoint analyses and safety analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01670981. Between April 2, 2013, and Jan 28, 2015, 126 participants were randomly assigned to receive either ixmyelocel-T (n=66) or placebo (n=60). 114 (90%) patients comprised the modified intention-to-treat population and 109 (87%) patients were included in the per-protocol primary efficacy analysis (58 in the ixmyelocel-T group and 51 in the placebo group). The primary efficacy endpoint was observed in 47 patients: 50 events in 25 (49%) of 51 patients in the placebo group and 38 events in 22 (38%) of 58 patients in the ixmyelocel-T group, which represents a 37% reduction in cardiac events compared with placebo (risk ratio 0·63 [95% CI 0·42–0·97]; p=0·0344). 41 (75%) of 51 participants in the placebo group had serious adverse events versus 31 (53%) of 58 in the ixmyelocel-T group (p=0·0197). To the best of our knowledge, ixCELL-DCM is the largest cell therapy study done in patients with heart failure so far. The transendocardial delivery of ixmyelocel-T in patients with heart failure and reduced ejection fraction due to ischaemic dilated cardiomyopathy resulted in a significant reduction in adjudicated clinical cardiac events compared with placebo leading to improved patient outcomes. Vericel Corporation.

Cell therapy is an evolving option for patients with end-stage heart failure. First-generation cell therapy trials have had marginal success. Our goal was to evaluate retrograde delivery of allogeneic umbilical cord subepithelial cells (UCSECs) in patients with heart failure. A prospective open-label dose escalation study of the safety and feasibility of UCSECs infused retrogradely into the coronary sinus was performed. Patients received a single dose of either 100 million (M), 200M, or 400M cells. The patients were followed for 2 years. Twenty-four patients were successfully enrolled in the study. The patients had UCSEC infusion without procedure-related complications. The ejection fraction in patients receiving UCSECs demonstrated improvement compared to baseline; from 25.4% (±5.5) at screening to 34.9% (±4.1) at 12 months. End-systolic diameter decreased significantly from 59.9 (±5.3) mm to 52.6 (±2.7) mm (p < 0.05). Retrograde UCSEC delivery was safe and feasible in all three dosage groups. Patients receiving 200M and 400M UCSECs showed signs of early improvement in left ventricular ejection fraction (LVEF) and remodeling. This study provides the basis for a larger clinical trial in heart failure (HF) patients using the middle or high dose of UCSECs.

Neonatal hypoxic-ischaemic encephalopathy (HIE) is a serious condition; many survivors develop neurological impairments, including cerebral palsy and intellectual disability. Preclinical studies show that the systemic administration of umbilical cord blood cells (UCBCs) is beneficial for neonatal HIE. We conducted a single-arm clinical study to examine the feasibility and safety of intravenous infusion of autologous UCBCs for newborns with HIE. When a neonate was born with severe asphyxia, the UCB was collected, volume-reduced, and divided into three doses. The processed UCB was infused at 12–24, 36–48, and 60–72 hours after the birth. The designed enrolment was six newborns. All six newborns received UCBC therapy strictly adhering to the study protocol together with therapeutic hypothermia. The physiological parameters and peripheral blood parameters did not change much between pre- and postinfusion. There were no serious adverse events that might be related to cell therapy. At 30 days of age, the six infants survived without circulatory or respiratory support. At 18 months of age, neurofunctional development was normal without any impairment in four infants and delayed with cerebral palsy in two infants. This pilot study shows that autologous UCBC therapy is feasible and safe.

Background Cesarean delivery has already become a very common method of delivery around the world, especially in low-income countries. Hypertrophic scars and wound infections have affected younger mothers and frustrated obstetricians for a long time. Mesenchymal stem cells (MSCs) have strong potential for self-renewal and differentiation to multilineage cells. Previous studies have demonstrated that MSCs are involved in enhancing diabetic wound healing. Therefore, this study is designed to investigate the safety and efficacy of using MSCs in the treatment of Cesarean section skin scars. Methods This trial is a prospective, randomized, double-blind, placebo-controlled, single-center trial with three parallel groups. Ninety eligible participants will be randomly allocated to placebo, low-dose (transdermal hydrogel MSCs; 3 × 10 6 cells) or high-dose (transdermal hydrogel MSCs; 6 × 10 6 cells) groups at a 1:1:1 allocation ratio according to a randomization list, once a day for six consecutive days. Study duration will last for 6 months, comprising a 1 week run-in period and 24 weeks of follow-up. The primary aim of this trial is to compare the difference in Vancouver Scar Scale rating among the three groups at the 6th month. Adverse events, including severe and slight signs or symptoms, will be documented in case report forms. The study will be conducted at the Department of Obstetric of Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan. Discussion This trial is the first investigation of the potential for therapeutic use of MSCs for the management of women’s skin scar after Cesarean delivery. The results will give us an effective therapeutic strategy to combat Cesarean section skin scars, even with uterine scarring. Trial registration ClinicalTrials.gov, NCT02772289 . Registered on 10 May 2016.

This study reports on 382 COVID-19 patients having undergone allogeneic ( n  = 236) or autologous ( n  = 146) hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0–80.3) for allogeneic, and 60.6 years (7.7–81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2–292.7) in allogeneic and 24.6 months (−0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age ( p  = 0.02), need for ICU ( p  < 0.0001) and moderate/high immunodeficiency index ( p  = 0.04) increased the risk while better performance status ( p  = 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19.

This study examines marketing claims of Canadian businesses engaged in direct-to-consumer advertising of putative stem cell treatments. Internet searches were used to locate Canadian businesses selling stem cell interventions. Company websites were subjected to detailed analysis. In total, 30 Canadian businesses sell stem cell interventions provided at 43 clinics. Autologous stem cells are the most common types of products promoted by such businesses. Company websites minimize risks while making strong claims about benefits of stem cell interventions. Businesses' representations could result in patients making health-related decisions informed by marketing claims rather than best available scientific evidence. Although there is absent development of new regulations and guidance, the Canadian direct-to-consumer marketplace for stem cell interventions appears poised for expansion.