The present study assessed the effects of intraportal infusions of autologous bone marrow-derived mononuclear cells (MNCs) and/or CD133+ cells on liver function in patients with decompensated cirrhosis. We randomly assigned 27 eligible patients to a placebo, MNCs, and/or CD133+ cells. Cell infusions were performed at baseline and month 3. We considered the absolute changes in the Model for End-Stage Liver Disease (MELD) scores at months 3 and 6 after infusion as the primary outcome. The participants and those who assessed the outcomes were unaware of the treatment intervention assignments. After 6 months, 9 patients were excluded because of liver transplantation (n = 3), hepatocellular carcinoma (n = 1), loss to follow-up (n = 3), and death (n = 2). The final analysis included 4 patients from the CD133+ group, 8 from the MNC group, and 6 from the placebo group. No improvement was seen in the MELD score at month 6 using either CD133+ cells or MNC infusions compared with placebo. However, at month 3 after infusion, a trend was seen toward a higher mean absolute change in the MELD score in patients who had received CD133+ cells compared with placebo (−2.00 ± 1.87 vs. −0.13 ± 1.46; p = .08). No significant adverse events occurred in the present study. A transient improvement in the MELD score was observed in subjects treated with CD133+ cells but not in the MNC or placebo group. Although the study was not powered to make definitive conclusions, the data justify further study of CD133+ therapy in cirrhotic patients.Significance: Cell therapy is a new approach in liver disease. Several clinical experiments have been reported on the safety of bone marrow-derived stem cells to treat liver disorders. However, the effectiveness of these approaches in the long-term follow-ups of patients initiated controversial discussions among the scientific community. A double-blind randomized controlled trial was designed to address this concern scientifically. A transient improvement in the patients' signs occurred; however, for a sustainable result, more work is needed. The results of multiple administrations of cells reported in the present study can be compared with the results from other single-injection studies.
Objective: Amyotrophic lateral sclerosis (ALS) is the most severe disorder within the spectrum of motor neuron diseases (MND) that has no effective treatment and a progressively fatal outcome. We have conducted two clinical trials to assess the safety and feasibility of intravenous (IV) and intrathecal (IT) injections of bone marrow derived mesenchymal stromal cells (BM-MSCs) in patients with ALS. Materials and Methods: This is an interventional/experimental study. We enrolled 14 patients that met the following inclusion criteria: definitive diagnosis of sporadic ALS, ALS Functional Rating Scale (ALS-FRS) >= 24, and >= 40% predicted forced vital capacity (FVC). All patients underwent bone marrow (BM) aspiration to obtain an adequate sample for cell isolation and culture. Patients in group 1 (n=6) received an IV and patients in group 2 (n=8) received an IT injection of the cell suspension. All patients in both groups were followed at 24 hours and 2, 4, 6, and 12 months after the injection with ALS-FRS, FVC, laboratory tests, check list of side effects and brain/spinal cord magnetic resonance imaging (MRI). In each group, one patient was lost to follow up one month after cell injection and one patient from IV group died due to severe respiratory insufficiency and infection. Results: During the follow up there were no reports of adverse events in terms of clinical and laboratory assessments. In MRI, there was not any new abnormal finding. The ALS-FRS score and FVC percentage significantly reduced in all patients from both groups. Conclusion: This study has shown that IV and IT transplantation of BM-derived stromal cells is safe and feasible.
The skin plays a crucial role as a protective barrier against external factors, but disruptions to its integrity can lead to wound formation and hinder the natural healing process. Scar formation and delayed wound healing present significant challenges in skin injury treatment. While alternative approaches such as skin substitutes and tissue engineering exist, they are often limited in accessibility and cost. Exosomes have emerged as a potential solution for wound healing due to their regenerative properties. In this study, exosomes were isolated from human blood serum using a kit. The exosomes were characterized, and their effects on cell migration were assessed in vitro. Additionally, the wound healing capacity of exosomes was evaluated in vivo using a rat full-thickness wound model. Our in vitro findings revealed that exosomes significantly promoted cell migration. In vivo experiments demonstrated that the injection of exosomes at different areas of the wound accelerated the wound healing process, resulting in wound closure, collagen synthesis, vessel formation, and angiogenesis in the wound area. These results suggest that exosomes have a promising therapeutic potential for expediting wound healing and minimizing scar formation. The findings of this study highlight the potential of exosomes as a novel approach for enhancing wound healing. Exosomes showed positive effects on both cell migration and wound closure in in vitro and in vivo studies, suggesting their potential use as a regenerative therapy for skin injuries. Further research is needed to fully understand the mechanisms underlying the beneficial effects of exosomes on wound healing and to optimize their application in clinical settings.
Objective: Glycogen synthase kinase-3β (GSK-3β) has been reported to be required for androgen receptor (AR) activity. This study sought to determine the usefulness of lithium chloride (LiCl) as a highly selective inhibitor of GSK-3β to increase the sensitivity of LNCap cells to doxorubicin (Dox), etoposide (Eto), and vinblastine (Vin) drugs. Materials and Methods: Thiazolyl Blue Tetrazolium Blue (MTT) assay was used to determine the cytotoxic effect to LiCl alone or in combination with low dose and IC 50 doses of drugs. Subsequently, cell cycle analysis was performed by using flow cytometry. Results: LiCl showed cytotoxic effect in a dose- and time-dependent manner ( P <0.001). Both Dox (100 or 280 nM) and Vin IC 50 (5 nM) doses caused G2/M-phase arrest ( P <0.001) compared with control. However, low dose (10 μM) or IC 50 (70 μM) Eto doses showed G2/M or S-phase arrests, respectively ( P <0.001). Combination of low dose or IC 50 dose of Eto with LiCl showed increased apoptosis as revealed by high percent of cells in SubG1 ( P <0.05, P <0.01, respectively). Moreover, Eto (10 μM) led to decreased percent of cells in G2/M phase when combined with LiCl ( P <0.05). Conclusion: This study showed that LiCl increases apoptosis of (LNCap) Lymph Node Carcinoma of the Prostate cells in the presence of Eto, which is S- and G2-phase-specific drug.