Acute myeloid leukemia (AML) is predominantly a disease of older patients with a poor long-term survival. Approval of the combination of venetoclax (VEN) with azacitidine (AZA) or decitabine (DAC) in the European Union in 2021 for the treatment of patients with newly diagnosed AML who are ineligible for induction chemotherapy has become the treatment backbone for older, medically non-fit AML patients. Based on in vitro priming of AML cells to all-trans retinoic acid (ATRA) by DAC, we had previously conducted a randomized phase II trial (DECIDER, AMLSG 14 - 09) in 200 elderly, non-fit AML patients on the effect of ATRA as add-on to DAC. Median overall survival (OS) was 8.2 months with ATRA versus 5.1 months without ATRA (hazard ratio, 0.65; 95% CI, 0.48 to 0.89; P = 0.006). Notably, ATRA did not add toxicity, the combination was active also in patients with adverse genetics, and prolonged time to treatment resistance. Investigating a triple combination of DAC, VEN and ATRA was a logical next step. This randomized double-blind phase III trial compares the efficacy of ATRA versus placebo as add-on to the backbone treatment (DAC and VEN) with respect to OS, objective best response, quality of life and safety. The accompanying translational research will contribute to identify molecular markers for drug efficacy and better tailoring epigenetic therapy.

The mobilization of peripheral blood stem cells(PBSC) needs daily injection of granulocyte colony stimulating factor (G-CSF), which brings inconvenience to healthy donors. Can pegylated granulocyte colony-stimulating factor (Peg-G-CSF) solve this problem by single dose injection?

Skin aging increases transepidermal water loss (TEWL), reduces elasticity, and perturbs the skin microbiome. Adipose tissue-derived stem cell exosomes (ASCE) show regenerative potential; however, their clinical effects on skin physiology and microbiome remain unclear. We conducted a split-face, randomized controlled trial in 16 adults aged ≥ 40 years with visible facial aging. One facial side received ultrasound-assisted transdermal delivery of a human ASCE-containing solution (HACS), whereas the other side received normal saline, at two-week intervals for three sessions. Biophysical outcomes (TEWL, stratum corneum hydration, and elasticity parameters R2/R5/R7) were assessed at baseline and week 2, 4, and 8. Wrinkles, pigmentation, and sebum levels were quantified using Mark-Vu imaging, and the Physician's Global Aesthetic Improvement Scale (PGAIS) and patient satisfaction assessment scores were recorded. Skin swabs from ten participants were subjected to 16S rRNA and ITS1 sequencing. HACS treatment significantly reduced TEWL (p = 0.006 at week 2; p = 0.009 at week 8) and increased hydration (p < 0.001 at all time points) with a significant increase in elasticity (R2/R5/R7 values, p < 0.001). Both the PGAIS and patient satisfaction scores were significantly higher on the experimental side. Bacterial α/β-diversity remained largely unchanged, and no bacterial taxa remained significantly associated with skin parameters after FDR correction. In contrast, several fungal taxa showed significant positive associations with skin parameters after FDR correction, detectable only on the HACS-treated side. No significant adverse events were observed. HACS improved barrier function, elasticity, and aesthetic outcomes, whereas microbiome analyses suggested a modest fungal response associated with treatment-related skin changes in aging skin.

Milk oligosaccharides (MO) support intestinal, microbial, and immune development in young pigs. However, modern production practices wean pigs at an early age, removing them from their source of MO prior to intestinal and immune maturation. The purpose of this study was to investigate the effects of dietary supplementation of galacto-oligosaccharides (GOS) and 2'-fucosyllactose (FL) on the jejunal mucosa-associated microbiota, intestinal immune signaling, morphology, and growth performance of nursery pigs. Forty-eight pigs (6.8 ± 0.2 kg body weight) weaned at 3-weeks-of-age were allotted into six dietary treatments, using a randomized complete block design, with sex and initial body weight as blocks. Dietary treatments were (1) basal diet; (2) basal diet, with supplemental GOS at 1.5% of the diet; (3) basal diet, with supplemental FL at 0.2% of the diet; (4) basal diet, with GOS and FL at 1.5 and 0.2% of the diet, respectively; (5) basal diet, with GOS at 2.3% of the diet; and (6) basal diet, with FL at 0.3% of the diet. These MO were provided alone or in combination at levels mimicking intake at the end of the suckling period, and at 1.5-fold higher, to observe potential dose-dependent responses. Pigs were fed for 21 days in two phases. On d 21, pigs were euthanized for sampling of jejunal mucosa and jejunal tissue. Data were analyzed using the PROC MIXED of SAS 9.4 and contrasts were used to determine the effects of GOS, FL, and their combination (interaction), in addition to the linear effects of increasing dietary GOS or FL. Increasing levels of GOS and FL linearly decreased (P < 0.05) Shannon and Simpson alpha diversity of the jejunal mucosa-associated microbiota. Supplementation with FL increased (P < 0.05) the absolute abundance of Helicobacter in the jejunal mucosa-associated microbiota, although no dose response was observed. Increasing levels of GOS and FL tended to linearly decrease (P = 0.051 and 0.076, respectively) the gene expression of TLR4. Increasing levels of GOS tended to increase (P = 0.054) and increasing supplementation of FL increased (P < 0.05) the number of Ki-67 proliferative cells in the crypt of the jejunum. Increasing levels of GOS increased (P < 0.05) body weight and average daily gain in the early post-weaning period and tended to increase (P = 0.093) body weight by the end of the experimental period. Notably, increasing levels of GOS, and GOS in combination with FL, improved growth performance, whereas FL alone did not.

To compare the outcomes of conjunctival graft (CAG) versus limbal-conjunctival autograft (LCAG) in preventing recurrence after surgery for recurrent pterygium with intraoperative application of 0.02% mitomycin C(MMC).

During the COVID-19 pandemic, Mesenchymal Stromal Cells (MSCs) were rapidly proposed as a therapeutic option for Acute Respiratory Distress Syndrome (ARDS) based on their immunomodulatory properties. We report the results of COVIDMES, a multicenter trial initiated within a public blood and tissue bank infrastructure during unprecedented period of volatility and scientific uncertainty of the first pandemic waves.

Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare genetic skin condition causing fragile skin, blistering, and scarring. It leads to chronic pain, slow wound healing, and severe limitations, profoundly impacting patient and family quality of life. Umbilical cord tissue-derived mesenchymal stromal cells (UC-MSC) have shown therapeutic promise. The Mission EB trial (ISRCTN14409785; registration date 25/03/2021) assessed UC-MSC safety and effectiveness in children with RDEB in a placebo-controlled, double-blinded, crossover study.

Atrophic acne scarring presents a significant therapeutic challenge with a profound psychosocial impact, and conventional treatments often yield suboptimal results. Autologous biologics, specifically stromal vascular fraction (SVF) and platelet-rich plasma (PRP), have emerged as promising regenerative strategies to address this issue.

This study aims to compare the efficacy of adipose-derived mesenchymal stem cells-enriched adipose extract (ARDE) with hyaluronic acid (HA) intra-articular injection in the treatment of temporomandibular joint osteoarthritis.

Severe COVID-19 is characterized by an aberrant immune response leading to systemic inflammation, organ dysfunction and high mortality among hospitalized patients. Mesenchymal stromal cells (MSCs), due to their immunomodulatory and tissue-reparative properties, are a potential therapeutic option. This study evaluated the safety of Wharton's Jelly-derived MSCs (WJ-MSCs) in patients with severe COVID-19 pneumonia.

Mitochondrial dysfunction contributes to poor embryo quality and recurrent assisted reproductive technology (ART) failure. Mitochondrial transplantation (MIT), which involves supplementing oocytes with exogenous mitochondria, has been proposed as a novel strategy to improve ART outcomes. However, both its clinical efficacy and safety remain unclear.

There is an unmet need for neuroregenerative therapies in multiple sclerosis (MS). Mesenchymal stem cells (MSCs) have shown immunomodulatory and regenerative effects in preclinical models and early clinical studies. Intrathecal administration may enhance therapeutic potential by direct delivery to the CNS. However, randomized, placebo-controlled trials are needed to establish safety and efficacy. The objective of this trial was to assess whether a single intrathecal administration of autologous MSCs could provide evidence of a neuroregenerative effect in progressive MS.

We completed an international, multicenter, randomized, open-label Phase I/IIb trial assessing the safety and preliminary efficacy of transendocardial injection of autologous expanded CD34+ cells (ProtheraCytes) in patients after acute myocardial infarction (AMI; NCT02669810). A multicenter, randomized, controlled Phase III study is now being initiated. To support release of ProtheraCytes clinical batches, we validated two flow cytometry methods for accurate quantification of CD34/CD45+ cells (stem cell enumeration-SCE method) and characterization of accessory leukocyte subsets (monocytes, granulocytes, and B, T, NK lymphocytes-accessory populations immunophenotyping method). All the recovery rates for both methods, with calculations derived from QC materials specifications, met the acceptance criteria, based on precision assessment according to ICH Q2(R2), European Pharmacopeia (Ph. Eur. 2.7.23 and Ph. Eur. 2.7.24), and ISHAGE guidelines. In addition, the precision results (repeatability and intermediate precision) were lower than 28.3% (≤ 30% for accessory populations immunophenotyping method) and lower than 13.5% (≤ 25% for SCE method). Finally, a perfect linearity was demonstrated for SCE method across 1.7-2622.5 cells/μL with coefficient of determination (R2) of linear regression above 0.99 and matrix effects nearly negligible for both methods. The specificity, precision and accuracy of these methods were proven in the analysis of six determinations per operator in three different series. Altogether, these results indicate a good accuracy and precision of the proposed methods determining absolute counts, viability, and proportions of live CD34/CD45+ cells and accessory populations. This validated flow cytometry assay will be implemented for release testing in the forthcoming Phase III clinical trial of ProtheraCytes in post-AMI patients.

The clinical need for treating anemia in aplastic anemia (AA) patients remains unmet. Luspatercept has been shown to be effective in myelodysplastic neoplasms (MDS).

Knee osteoarthritis (KOA) is a degenerative joint condition characterized by progressive cartilage deterioration and chronic pain, leading to functional impairment. Bone marrow-derived orthobiologics, such as bone marrow aspirate clot (BMA-clot) and bone marrow aspirate concentrate (BMAC), have emerged as promising regenerative therapies. Despite their growing clinical use, no randomized clinical trials to date have directly compared the efficacy and safety of these two approaches in patients with KOA, leaving a gap in the current evidence base. This study aimed to compare the efficacy and safety of intra-articularBMA-clot and BMAC in patients with moderate to severe KOA over a 12-month follow-up period. In this prospective, randomized, double-blind clinical trial, patients aged 50-80 years with Kellgren-Lawrence grade 3-4 KOA were enrolled. Participants received thr ee monthly intra-articular injections of eitherBMA-clot or BMAC. The primary outcome was functional improvement assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes included pain reduction (Visual Analog Scale) and quality of life (Short Form-36, SF-36). Adverse events were monitored, and data were analysed using mixed-effectsmodels. Both treatments resulted in significant improvements in pain, function, and quality of life throughout the 12-month period. Clinical outcomes between the BMA-clot and BMAC groups were not statistically different. The incidence of adverse events was low, with no serious complications observed. Intra-articular administration of BMA-clot and BMAC appears to be safe and effective for the management of moderate to severe KOA, providing sustained symptom relief and functional gains over a 12-month period. Given its simpler preparation and lower cost, BMA-clot may represent a more accessible therapeutic option in clinical settings.

Knee osteoarthritis (KOA) is a progressive degenerative joint disease with limited treatment options that effectively modify disease progression. This study evaluates the safety and efficacy of allogeneic adipose-derived mesenchymal stromal cells (ADMSCs) injected under ultrasound guidance in patients with symptomatic stage III KOA. In this single-site, randomized, double-blind, placebo-controlled trial, patients were assigned to receive either 2 doses of allogeneic expanded ADMSCs, administered 2 weeks apart (Arm A, mean total dose: 69.58 × 106 ADMSCs), or 2 equal-volume normal saline injections (Arm B). Blinding was maintained for 12 months, after which follow-up of Arm A continued to 60 months. Treatment efficacy was assessed using normalized Knee Injury and Osteoarthritis Outcome Score and Western Ontario and McMaster Universities Osteoarthritis Index at 6, 12, 24, 36, 48, and 60 months, while magnetic resonance imaging (MRI) evaluations were performed at baseline and 12 months. A total of 29 subjects (21 in Arm A, 8 in Arm B) completed the study. Adverse events in Arm A were mild and transient, including localized pain and swelling. Patients in Arm A demonstrated significant improvements in clinical scores compared to baseline, with highly significant differences at 6, 12, 24, and 36 months (P < .0001). MRI assessments at 12 months revealed structural improvement (P < .02). However, clinical improvements declined steadily after 36 months, with scores nearing baseline at 60 months. These findings suggest that allogeneic ADMSC therapy is safe and provides sustained clinical and structural benefits for up to 3 years. Larger trials are needed to optimize dosing and assess long-term efficacy.

BACKGROUND: Disrupted immunity and microbiota dysbiosis underlie the pathophysiology of preterm complications. This study investigated the effect of autologous cord blood (ACB)-mononuclear cells (MNCs) infusion, rich in stem cells, on immune microecology in very preterm infants (VPIs). METHODS: One twin from each enrolled very preterm monozygotic pair was randomized to receive an ACB-MNCs infusion or normal saline. Immune cells, inflammatory cytokine profiles, and gut/lung microbiota, were compared. Short- and long-term clinical outcomes were evaluated. RESULTS: ACB-MNCs intervention induced transcriptional up-regulation of regulatory T cells (Treg) differentiation-facilitating genes and increased circulating Tregs. In blood, post-ACB-MNCs infusion, pro-inflammatory factors decreased, while the IL-10 level was higher than in the control group. In the ACB-MNCs group, lung microbial diversity increased significantly after intervention. Post-intervention, lung IL-10 and TGF-β increased in the ACB-MNCs group and were higher than the control group, while pro-inflammatory factors IL-4, IL-17 A, and IL-6 levels decreased in the ACB-MNCs group. In the ACB-MNCs group, gut microbial diversity improved and was more metabolically active after intervention. After intervention, mainly upregulated differentially expressed genes in peripheral blood immune cells were positively correlated with favored microbes colonizing the lung. Lung IL-10 correlated positively with blood Treg frequency, while lung IL-10 and TGF-β correlated negatively with blood IL-17A. The gut microbial diversity was negatively associated with blood IL-17A. Compared with control group, the total number of distinct preterm complications per patient in the ACB-MNCs group were fewer and long-term linear growth was better. CONCLUSION: ACB-MNCs intervention promoted immunity homeostasis via modulation of Treg and lung/gut microbiota. TRIAL REGISTRATION: This study was registered at Clinicaltrials.gov (NCT05087498). Date of registration: 10/09/2021; date of enrollment of the first participant to the trial:11/28/2021URL of trial registry record: https://clinicaltrials.gov/study/NCT05087498?term=NCT05087498&rank=1 .

A Phase 3 randomized trial compared immunosuppressive therapy with or without eltrombopag in untreated patients with aplastic anemia (AA) and showed that addition of eltrombopag increased the rate, rapidity, and durability of hematological response, without increasing transformation to myeloid malignancies. We sought to systematically investigate clonal hematopoiesis (CH) dynamics from patient samples from this trial.

Frailty syndrome in older adults is a growing public health concern associated with increased vulnerability and adverse outcomes. Umbilical cord-derived mesenchymal stem cell (UC-MSC) therapy shows promise in improving physical function and quality of life. This study evaluated the safety and efficacy of intravenous UC-MSC infusion in older frail adults.

In ischemic heart failure, the biological mechanisms underlying the benefits of mesenchymal stromal cells (MSCs) and c-kit-positive cardiac progenitor cells (CPCs) remain incompletely understood.