&lt;b&gt;Background and Objective:&lt;/b&gt; Diabetic foot ulcers (DFUs) remain a critical clinical problem and stem cell-derived secretome reared under hypoxic conditions has been shown to play a significant role in tissue repair via immunomodulation. This study aimed to evaluate the secretome of human mesenchymal stem cell gel (SH-MSC gel) in DFU patients with grades 2 and 3 through reduced wound volume and modulation of CD163 and NF-κB p50 mRNA expression. &lt;b&gt;Materials and Methods:&lt;/b&gt; A prospective, randomized controlled clinical trial involved 16 DFU patients with grades 2 and 3. Participants received either a placebo gel or an intervention gel containing secretome from Human Umbilical Cord Mesenchymal Stem Cells (hUC-MSCs) cultured under hypoxic conditions. All patients received standard wound care. Primary outcomes included changes in wound volume and expression levels of CD163 and NF-κB p50 mRNA in wound tissue, assessed using quantitative PCR. The Shapiro-Wilk test assessed normality and for normally distributed data, paired t-tests (within-group) and unpaired t-tests (between-group) were used. One-way ANOVA compared means across groups, while the Kruskal-Wallis test followed by &lt;i&gt;post hoc&lt;/i&gt; analysis was employed for non-parametric data (p<0.05). Statistical analysis was performed using GraphPad Prism 10. &lt;b&gt;Results:&lt;/b&gt; Baseline characteristics of participants did not show significant differences between the groups. Treatment with SH-MSC gel significantly enhanced wound healing compared to the placebo group, evidenced by a marked reduction in wound volume after 7 days (95% CI (0.467 to 1.18), p<0.001). The CD163 mRNA expression significantly increased in the SH-MSC gel group post-treatment (95% CI (-2.20 to -1.11), p<0.001), while NF-κB p50 mRNA expression significantly decreased (95% CI (0.349 to 0.688), p<0.001). &lt;b&gt;Conclusion:&lt;/b&gt; The clinical trial results suggested that SH-MSC gel effectively improves wound healing in DFUs. Further research is warranted to explore additional inflammatory markers to better understand DFU treatment.

Background: Exosomes (Exos) derived from mesenchymal stem cells (MSCs) share similar biological functions with MSCs but are more stable under various pathophysiological conditions, with a lower risk of immune rejection. Human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising source of MSC-derived exosomes (MSC-Exos), particularly for the treatment of osteoarthritis (OA), a degenerative joint disease characterized by inflammation and cartilage damage.

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are recognized as a promising strategy for cell-free therapy, however, their therapeutic role in pulmonary fibrosis remains unrevealed. Here, we report the safety and efficacy of MSC-EVs from human umbilical cord (hUCMSC-EVs) evaluated in mouse models and pulmonary fibrosis patients. We established a rigorous system to produce high-quality of hUCMSC-EVs, characterized by miRNA, protein, and metabolite profiles. When administered via nebulization, hUCMSC-EVs predominantly accumulated in murine lungs and ameliorated bleomycin-induced pulmonary fibrosis, with increased survival rate (from 20% to 80%), restored lung volume, and attenuated injury severity accompanied by elevated oxyhemoglobin saturation and improved pulmonary function evaluations. We performed a phase l clinical trial involving twenty-four patients in a randomized, single-blind, and placebo-controlled study to treat pulmonary fibrosis (MR-46-22-004531, ChiCTR2300075466). All participants tolerated the nebulized hUCMSC-EVs well, with no serious adverse events. Patients receiving the combined therapy of nebulized hUCMSC-EVs and routine treatment demonstrated significant improvements in both lung function indices (forced vital capacity and maximal voluntary ventilation) and respiratory health status (as measured by the Saint George's Respiratory Questionnaire and Leicester Cough Questionnaire. Overall, patients upon the additional therapy with nebulized hUCMSC-EVs gained significant benefits compared with those accepted only routine treatment. Remarkably, two patients with advanced post-inflammatory pulmonary fibrosis exhibited clinically significant regression on serial CT scans after hUCMSC-EVs therapy. These findings suggest that nebulized hUCMSC-EVs could be used as a promising therapeutic strategy for treating pulmonary fibrosis diseases.

Pediatric cancer patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are severely immunosuppressed leading to a high risk for life-threatening infections. This trial investigates the effects of exercise during allo-HSCT on immune cell recovery and patient-related outcomes (DRKS00019865).

This study evaluated the effectiveness of intrathecal autologous bone marrow mononuclear cell (BMMNC) therapy combined with education compared with education alone for the treatment of autism spectrum disorder (ASD).

Clonal hematopoiesis of indeterminate potential (CHIP), characterized by age-related somatic mutations in hematopoietic stem and progenitor cells, has been identified as a potential risk factor for cardiovascular events and mortality. However, the significance of CHIP in the context of coronary artery bypass grafting (CABG) remains unexplored. We aim to investigate the potential impact of CHIP on long-term outcomes of patients who underwent CABG.

Injectable platelet-rich fibrin (I-PRF) is an autologous fibrin matrix rich in leucocytes, platelets and growth factors, and could serve as a sustained-release vehicle for a variety of active biomolecules. The aim of the current randomized controlled trial was to compare the effect of vitamin C (VitC) with I-PRF as a locally delivered adjunct to professional mechanical plaque removal (PMPR) versus PMPR with local delivery of I-PRF or PMPR alone on non-surgical periodontal treatment (NSPT) outcomes of stage-II periodontitis.

Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disorder affecting salivary and lacrimal glands, leading to distressing ocular symptoms. Existing therapeutic approaches for SS-associated dry eye syndrome (DES) show insufficient efficacy. This study investigates the use of topical MSC-derived exosomes in primary SS-related DES.

This study investigated the safety and efficacy of MR-MC-01, a mesenchymal stem cell therapy derived from human embryonic stem cells, in patients with interstitial cystitis (IC), particularly those with Hunner lesions unresponsive to pentosan polysulfate sodium (PPS). Conducted as a prospective, randomized, double-blind, placebo-controlled phase I/IIa clinical trial, it enrolled 22 patients, with six completing phase I and 16 participating in phase IIa. Phase I tested 2 doses (2.0 × 107 and 5.0 × 107 cells) to determine the maximum tolerated dose (MTD), revealing no dose-limiting toxicities and only mild adverse events such as transient hemorrhage and bladder pain. In phase IIa, 12 participants received the MTD of 5.0 × 107 cells, and 4 received placebo. Significant reductions in interstitial cystitis questionnaire (ICQ) and pain urgency frequency (PUF) scores were observed in the treatment group. Improvements were noted in nocturnal voiding frequency and Hunner lesion size, with 8 patients showing either a reduction or complete resolution of lesions after 6 months. The global response assessment (GRA) reported moderate to marked improvement in 41.67% of treated patients versus 25% in the placebo group. MR-MC-01 demonstrated no serious drug-related adverse events, highlighting its favorable safety profile. These findings suggest that MR-MC-01 not only alleviates symptoms but also promotes structural recovery in IC, making it a promising treatment option. Further large-scale, long-term studies are warranted to confirm these results and optimize therapeutic protocols. (Identifier: NCT04610359).

Pancreatic cancers involve several challenges from difficulty in early diagnosis to high recurrence and mortality even after therapeutic interventions. Patients who undergo a surgical resection have several postoperative complications besides recurrence. Immunosuppression in the peri-operative period is a major challenge to overcome and in this study we investigated the effects of AFO-202 strain Aureobasidium-pullulans produced β-glucan (Nichi BRITE) in patients who underwent subtotal stomach-preserving pancreaticoduodenectomy (SSPPD) for pancreatic, bile duct and duodenal malignancies.

In this single-center, double-blinded, randomized controlled trial, we investigated whether human umbilical cord-derived mesenchymal stromal cells loaded collagen scaffolds (hUC-MSC/CS) could improve the cumulative live-birth rate (cLBR) in infertile women with refractory thin endometrium (RTE). We randomly assigned 25 subfertile women with RTE, in a 1:1 ratio, to receive hysteroscopic adhesiolysis and plowing plus either hUC-MSC/CS or saline/CS (control) for intrauterine implantation. Uterine fluid was collected on the embryo transfer day for RNA-sequencing to explore the potential mechanisms by which hUC-MSCs exert their effects. The primary outcome was the cLBR. Live births occurred in 3 out of 11 women in the hUC-MSC/CS group and in 1 out of 13 women in the control group (27.3% vs 7.7%; relative risk [RR], 3.55; 95% confidence interval [CI], 0.43 to 29.42; P = .30). The cumulative frequencies of clinical pregnancy were 5/11 and 1/13 in the hUC-MSC/CS group and control group, respectively (45.5% vs. 7.7%; RR, 5.91; 95% CI, 0.81-43.28; P = .06). Two of 11 participants developed urticaria in the hUC-MSC/CS group. Enrichment analysis showed that T-cell activation had the largest proportion in the biological process category. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that most genes were related to cytokine-cytokine receptor interaction. In conclusion, there was a non-significant trend toward a higher cLBR with hUC-MSC/CS compared to controls, potentially through the cytokine-cytokine receptor interaction pathway. hUC-MSCs appeared to be relatively safe in a 1-year follow-up. Therefore, this novel therapy can be proposed to patients with RTE.

Osteoarthritis (OA) is a degenerative joint disease that primarily affects older adults, characterized by cartilage degradation, synovitis, and osteophyte formation. Despite its prevalence, no medical treatment can reverse the joint cartilage degradation, leading many patients to undergo invasive procedures such as arthroplasty. Mesenchymal stem cells (MSCs), particularly those derived from adipose tissue, have emerged as a promising therapeutic approach due to their ability to differentiate into chondrocytes and potentially regenerate cartilage. While MSCs from bone marrow and umbilical cord have shown efficacy in treating OA, adipose-derived MSCs (ADMSC) are more accessible and cost-effective. This study aims to evaluate the safety and efficacy of allogeneic ADMSC in treating knee OA.

Remote ischemic conditioning (RIC) is a simple and low-cost intervention that is thought to increase collateral blood flow through the vasodilatory effects of nitric oxide (NO) produced by the endothelium and red blood cells (RBCs). The aim of this study was to investigate whether RBC form and function are associated with short- and long-term outcomes in patients with acute ischemic stroke, and whether RIC treatment modified this effect.

Umbilical cord mesenchymal stem cell-derived (UCMSC-derived) secretome is anti- apoptotic, anti-inflammatory, antifibrotic, angiogenic, and tissue-regenerating. Thus, it may treat systemic lupus erythematosus (SLE). The aim of this study was to investigate the impact of the UCMSC-derived secretome on SLE patients' disease activity, using Mexican systemic lupus erythematosus disease activity index (MEX-SLEDAI) score, complement (C3 and C4) levels, tumor necrosis factor-alpha (TNF-α), anti-double-stranded DNA (anti-dsDNA), and interleukin-6 (IL-6) levels. This double-blind randomized controlled trial investigated the efficacy and safety of UCMSC-derived secretome in SLE patients with moderate disease activity. A total of 29 female patients were randomized into two groups to receive weekly 1.5 cc intramuscular injections of UCMSC-derived secretome or placebo (0.9% NaCl) for six weeks. Disease activity was assessed using the MEX-SLEDAI score, C3 and C4 levels, pro-inflammatory cytokines (IL- 6 and TNF-α), and anti-dsDNA antibodies at baseline, Day 22, and Day 43. Results showed a significant reduction in MEX-SLEDAI scores in the secretome group compared to the placebo group (p < 0.05). Complement C3 levels significantly increased in the secretome group on Day 43, indicating improved immune homeostasis, while C4 levels did not show significant differences between groups. IL-6 and TNF-α levels showed decreasing trends in the secretome group. Anti-dsDNA levels exhibited a decreasing trend in the secretome group, though not statistically significant. Importantly, no severe adverse events were observed, underscoring the safety of the intervention. UCMSC-derived secretome demonstrated immunomodulatory and anti-inflammatory effects, reducing disease activity in SLE patients. These findings suggest its potential as a safe and effective adjunct therapy for SLE, although further studies with larger sample sizes and extended follow-up periods are needed to validate these results.

Neonatal hypoxic ischemic encephalopathy (nHIE) is a serious disease that causes severe and chronic neurological damage. Hypothermia therapy improves patients' outcomes albeit with some limitations, but combining it with treatment with cord blood cells (analogous to mesenchymal stem cells [MSCs]) reportedly improves its effectiveness. TEMCELL HS Inj. (Temcell), a human bone marrow-derived MSC product used for acute graft-versus-host disease, seems an appropriate candidate for this combination therapy. Therefore, we performed a randomized, parallel-group study to compare combined treatment with Temcell and hypothermia versus hypothermia therapy-alone to evaluate the safety and efficacy of Temcell in nHIE patients. The primary endpoint was treatment response defined as an overall developmental quotient of ≥ 85 at 18 months of age. Fourteen patients were enrolled and randomized, with 7 assigned to each group. Both groups had similar demographic characteristics and nHIE severity. Treatment response was observed in 4 of the 6 (66.7%) patients in the Temcell combination group, and in 4 of the 7 patients (57.1%) in the hypothermia therapy-alone group. No marked differences in safety profile were observed between the groups. These results indicate that the efficacy of Temcell combined with hypothermia is comparable to therapeutic hypothermia for patients with nHIE.Clinical Trial Registration: jRCT1080224818.

Aim: To determine the effectiveness of a multidisciplinary rehabilitation program (MRP), integrating mesenchymal stem cells (MSCs) therapy, acupuncture, physiotherapy and physical exercises, in improving the functional recovery in patients with combat-related injuries and chronic critical lower limb ischemia (CCLLI).

This phase 2 study evaluated the impact of pegfilgrastim, a single-dose, long-acting granulocyte colony-stimulating factor, on the steady-state mobilization of hematopoietic stem cells into peripheral blood in patients with multiple myeloma (MM) or malignant lymphoma (ML). Efficacy and safety, along with CD34-positive cell mobilization outcomes were assessed in patients with MM, who were randomly assigned to pegfilgrastim (n = 30) or daily filgrastim (n = 31), and ML (pegfilgrastim only, n = 13) cohorts. In the MM cohort, CD34-positive cell counts ≥ 2 × 106/kg were achieved in 100% of patients in the pegfilgrastim group and 96.7% in the filgrastim group (difference: 3.3%; 80% confidence interval: -0.9-7.5%), demonstrating the non-inferiority of pegfilgrastim to filgrastim. All patients in the ML cohort achieved ≥ 2 × 106/kg CD34-positive cell counts. The plerixafor administration rates in the MM cohort were 50.0% and 63.3% in the pegfilgrastim and filgrastim groups, respectively, and 91.7% in the ML cohort. There were no major differences in safety measures between the two groups. Although the sample size was small, particularly in the ML cohort, a single dose of pegfilgrastim demonstrated comparable efficacy and safety to daily doses of filgrastim, indicating its potential for clinical use while reducing patient burden.Trial Registration: jRCT2011210029, NCT05007652.

The aim of this open-label, multicenter, randomized controlled trial was to determine the efficacy and safety of sequential umbilical cord-derived mesenchymal stem cell (UC-MSC) infusion for graft-versus-host disease (GVHD) prevention within 3 months of haploidentical hematopoietic stem cell transplantation (haplo-HSCT).

Intrathecal injection (IT) of autologous mesenchymal stem cells (MSC) showed robust beneficial effects a previous randomized study from our center, in patients with progressive multiple sclerosis (MS) (NCT02166021). We evaluated here the effect of repeated MSC-NG01 transplantations on serum biomarkers of neuroinflammation and neurodegeneration, namely, neurofilaments light chains (NFL) and glial fibrillary acidic protein (GFAP), in an open-label extension trial.

Autologous fat grafting is widely used in reconstructive surgery and its use is increasing in different areas of regenerative medicine. This study evaluates the impact of elliptical lipoaspirate activation on adipose tissue grafting outcomes, focusing on scar-related pain reduction, improved scar characteristics, and increased tissue elasticity, comparing these outcomes with the traditional Coleman method.