Current stem cell research & therapy最新文献

Introduction: The toxicity, high cost, and negative side effects of conventional treatments of Rheumatoid Arthritis (RA) highlight the necessity for more effective and safer therapeutic options.

Methods: Rutin-loaded Chitosan/Pectin Nanoparticles (RT-CPN) were synthesized via a modified ionic gelation technique and characterized by various physicochemical methods. Exosomes (EXO) were isolated from mesenchymal stem cells-conditioned media and characterized. Six groups (n = 10) were used to evaluate the treatment's effectiveness in a CFA-induced rat arthritis model. Normal control, arthritic control, and arthritic groups treated with Rutin (RT) (20 mg/kg), EXO (100 μg protein/ rat, weekly i.v.), RT-CPN (20 mg/kg), and RT-CPN+EXO. Treatment lasted 28 days, after which, ankle circumference was recorded, serum and joint tissues were collected for molecular and histopathological analysis.

Results: Treatment with RT, EXO, RT-CPN, and EXO+RT-CPN significantly reduced ankle swelling, serum RF, PGE2, ROS, and TNF-α, while increasing IL-4. They also downregulated NF-κB p50, IκBα, TNFR, P53, and caspase-3 expression. Gross morphologically, leg swelling and redness declined, and ankle joint histological investigation showed reduced pannus formation, inflammation, synovial hyperplasia, and cartilage degradation.

Discussion: Both EXO and RT-CPN demonstrated potent anti-arthritic effects by regulating inflammation, oxidative stress, and apoptosis (both extrinsic and intrinsic). They worked best together, probably because of their synergy.

Conclusion: The EXO+RT-CPN combination showed the most potent anti-arthritic effect, mediated by suppressing oxidative stress and by anti-inflammatory and anti-apoptotic mechanisms. This suggests the therapeutic potential of combination therapies in arthritis treatment.

Introduction: Sedative doses of propofol have recently been reported to exert positive effects on the developing brain, potentially enhancing later cognitive function, but the underlying mechanism remains unclear. This study aims to investigate changes in cell cycle status and reveal the dominant upstream molecular cascade following sedative-dose propofol treatment of primary neural stem cells (NSCs) in vitro.

Methods: Primary C57BL/6 murine NSCs were isolated and cultured. Proliferation was assessed using CCK-8 assays, direct cell counting, and EdU labeling after exposure to 10 μM propofol. Cell cycle distribution was analyzed by flow cytometry. Bulk RNA sequencing, qRT-PCR, and western blotting were used to explore potential pathways. FoxO3a overexpression via adenovirus was employed to confirm the mechanism.

Results: Primary NSCs, identified with >95% Nestin positivity, were successfully isolated. Propofol at 10 μM enhanced NSC proliferation as assessed by CCK-8 assays, cell counting, and immunofluorescence. Cell cycle analysis revealed that propofol promotes G1-S phase transition in NSCs. FoxO3a, a crucial component of the redox signaling pathway, was downregulated after propofol exposure, along with its downstream regulator p27. Importantly, FoxO3a overexpression counteracted propofol's effects on cell cycle distribution and NSC proliferation.

Discussion: These findings indicate that propofol promotes NSC proliferation by inhibiting FoxO3a nuclear translocation, a key mechanism driving the G1-S transition. This effect is concentrationdependent and occurs at clinically relevant sedation levels, highlighting its potential neuroprotective role. The cellular context and specific signaling mediators of the FoxO3a-p27 axis warrant further investigation.

Conclusion: In summary, this study confirms the FoxO3a-p27 axis as a key pathway mediating propofol's proliferative effects on NSCs at sedative concentrations.

Introduction: Numerous studies on HIV (human immunodeficiency virus) in stem cells have been published over the last two decades. However, no comprehensive bibliometric analysis or visualization of this field currently exists. This study aims to provide a detailed and unbiased review of the knowledge structure, research hotspots, and emerging trends in stem cell therapy-related research for HIV. By mapping publication trends, collaboration networks, and topical evolution, this work fills a critical gap and offers guidance for future functional cure strategies.

Methods: Bibliometric data from 2004 to 2023 were retrieved from the Web of Science Core Collection database. CiteSpace was used to analyze annual scientific output, countries/regions, institutions, authors, journals, references, and keywords.

Results: A total of 2,868 publications were included, showing a general trend of increasing yet fluctuating annual output. The United States led in both publications and influence, while author collaboration remained relatively limited. Key research topics included acquired immune deficiency syndrome cure, lentivirus, HIV carcinogenicity, CCR5, and CXCR4. More recently, major active areas of investigation have focused on "extracellular vesicles," "nucleases," "viral libraries," and "microglia."

Discussion: HIV stem cell research has progressed from descriptive studies to mechanism-driven approaches, emphasizing gene editing and immune modulation. Integrating stem cell transplantation with technologies such as CRISPR/Cas9 presents a promising strategy to eliminate viral reservoirs and sustain remission. Nevertheless, stronger international collaboration and translational research are essential to advance clinical applications.

Conclusion: This comprehensive bibliometric overview provides clear insights into the development, research hotspots, and trends in HIV stem cell therapy. Further investigation into the molecular mechanisms of infection and strategies for functional cure may accelerate the development of effective stem cell-based gene therapies for HIV.

Introduction: Umbilical cord blood-derived exosomes have been considered an excellent resource for regenerative medicine and cancer therapy. These exosomes induce various therapeutic activities through specific cellular responses and molecular signaling mechanisms. In the present study, we investigated the biological effects of exosomes derived from cord blood mononuclear cells (CB-MNCs) and cord blood plasma (CBP) on the U937 cell line, a human acute myeloid leukemia (AML) model.

Methods: After cord blood collection, the cord blood units were processed to harvest CBP and CBMNCs. Exosomes were then isolated, purified, and identified by transmission electron microscopy, dynamic light scattering, and Western blotting. Subsequently, U937 cells were cultivated and exposed to the exosomes for 72 hours. Apoptosis and proliferation were assessed by flow cytometry, caspase-3/7 activity assays, and quantitative real-time PCR (qRT-PCR). Moreover, NF-κB and AMPK signaling pathway activity was evaluated by Western blotting.

Results: We showed that exosomes from CB-MNCs significantly induced apoptosis, triggered caspase- 3/7 activity, and upregulated the expression of pro-apoptotic genes in U937 cells compared with exosomes from CBP. In addition, CB-MNC-derived exosomes efficiently inhibited NF-κB signaling and activated the AMPK pathway.

Discussion: The observed pro-apoptotic effects and pathway modulation indicate that CB-MNCderived exosomes exert stronger anti-leukemic activity than CBP-derived exosomes. These variations could be attributed to the molecular cargo carried by each exosome population and suggest that the cellular source is a significant factor in exosome-based therapeutics.

Conclusion: These findings suggest that exosomes derived from CB-MNCs could be a potent antileukemic agent and a promising novel therapeutic approach for AML.

Introduction: Chronic pain and high disability rates caused by osteoarthritis (OA) significantly impact quality of life. Programmed cell death (PCD) plays a crucial role in OA pathogenesis; however, a comprehensive analysis of PCD patterns in OA is lacking, limiting understanding of their potential role.

Methods: Batch transcriptomic data related to OA were obtained from the GEO database. Differential expression analysis based on 13 PCD patterns was performed to identify differentially expressed genes (DEGs). Unsupervised clustering algorithms were applied to define molecular subtypes associated with OA. The CIBERSORT algorithm was used to analyze the immune microenvironment and evaluate the immunological relevance of each cluster. Hub PCD-related DEGs were identified using a combination of machine learning algorithms, and an OA diagnostic model was constructed based on these hub genes. Single-cell RNA sequencing (scRNA-seq) dataset GSE169454 was used to classify OA chondrocytes into distinct cell clusters. The AddModuleScore function calculated PCD scores, allowing evaluation of hub-gene expression and PCD variation across clusters. Expression levels of ten hub PCD-related DEGs were further validated in OA cells and rat models.

Results: Differential expression analysis identified 61 PCD-related DEGs. Unsupervised clustering revealed two molecular subtypes of OA (cluster 1 and cluster 2), with immune-related pathways significantly enriched in cluster 1, including potential NK cell activation. Ten hub PCD-related DEGs were identified using three machine learning algorithms, leading to a highly effective diagnostic model (AUC = 0.993). Five distinct cell types were identified in OA chondrocytes, with higher PCD scores observed in OA samples and the HomC subgroup. Functional analysis indicated significant enrichment of the PI3K-AKT signaling pathway in high BINP3-expressing preHTCs, associated with extracellular matrix composition. mRNA and protein levels of the ten hub DEGs were confirmed in animal models.

Conclusion: This multi-omics analysis of 13 PCD patterns provides a preliminary evaluation of the diagnostic and classification value of PCD-related genes in OA, highlighting potential biomarkers for clinical application.

Treating breast cancer has been quite a challenge due to drug resistance and the complexity of the tumor microenvironment. Moreover, the non-specificity of chemotherapeutic agents confers side effects while treating aggressive subtypes like triple-negative breast cancer. While targeted therapies are evolving, novel cellular therapies have a promising scope for treating breast cancer, as they can be tailored and allogeneic. Tailored cellular therapies face challenges such as cell availability and the cost of development as well as deployment. While allogeneic cellular therapies overcome these disadvantages, they face graft-versus-host disease. To overcome this, cells with no MHC-I and II, or less immunogenic cells with anti-cancer abilities, are attractive choices. One such cell type is the multipotent mesenchymal stromal cell (MSC). These cells are less immunogenic, have immunomodulatory properties, and are also known to home to tumor sites. Such properties can enable their exploitation for delivering drugs and other biotherapeutics. In addition, they seem to possess a natural tumor-inhibiting capability. However, it may be dependent on a multitude of factors, including cancer type, stage of presentation, and the tumor microenvironment. This review examines the fundamental biological mechanisms behind the anti-breast cancer effects of mesenchymal stem cells (MSCs), summarizes current advances in MSC-based therapeutic approaches for breast cancer, and explores the potential of genetically engineered MSCs in treatment, while identifying the existing research and application gaps.

Introduction: To investigate the protective mechanism of Qishen Yiqi Dropping Pills (Qishen) and its key active ingredients in combination with exosomes from bone marrow mesenchymal stem cells (BMSCs) against myocardial ischemia/reperfusion (I/R) injury.

Methods: Infarct area was assessed by Evan's Blue/TTC double staining, myocardial apoptosis was analyzed by TUNEL staining, ATP content and NAD+/NADH ratio were detected biochemically, macrophage phenotype of myocardial tissues was detected by flow cytometry, activation of the mTOR/PI3K/Akt pathway was detected by Western blotting, and miR-155-5p expression was detected by qRT-PCR. 155-5p expression. Exo were given to identify the M1/M2 phenotypic transition by immunofluorescence, and the molecular mechanism was verified as in the in vivo experiments.

Results: Compared with the model group, the Qishen, ginsenoside, and Exo group significantly reduced the infarcted area of the heart and promoted M2 and M2 phenotypic conversion, promoted M2- type macrophage infiltration, up-regulated the p-Akt/Akt ratio, and inhibited the expression of miR- 155-5p, but the combination therapy group did not show a synergistic effect, but the above protective effects were significantly weakened by the removal of macrophages. Ginsenoside and Exo synergistically promoted M2 polarization, activated the mTOR/PI3K/Akt pathway and upregulated miR-155-5p expression.

Discussion: Qishen, particularly its active component ginsenoside, synergizes with BMSC-Exo to alleviate myocardial I/R injury by modulating macrophage polarization via the miR-155- 5p/mTOR/PI3K/Akt signaling axis.

Conclusion: Qishen synergistically regulates the miR-155-5p/mTOR/PI3K/Akt signaling axis through ginsenoside components in BMSCs exosomes, promoting macrophage polarization toward M2-type, improving myocardial energy metabolism and attenuating I/R injury, and this protective effect is macrophage-dependent.

Introduction: Acute Spinal Cord Injury (SCI) often causes motor and sensory deficits. SDF-1 promotes stem cell survival and proliferation, while FBN1 may impact repair mechanisms. This study investigates how SDF-1 promotes SCI treatment by inducing BMSC maturation through BMP-8-mediated FBN1 inhibition.

Methods: Bone marrow mesenchymal stem cells were induced to differentiate with BMP-8 and transfected with related plasmids (oe-NC, oe-SDF-1, oe-FBN1, si-BMP-8). CCK-8 and alizarin red staining were used to assess cell growth and differentiation. Western blotting was used to detect the levels of SDF-1, FBN1, and BMP-8. In a rat SCI model, cells with plasmids were injected, and motor recovery was assessed using BBB scoring. Immunofluorescence assay detected SDF-1 expression, while Western blotting was used to detect SDF-1, FBN1, and BMP-8.

Results: In cell experiments, BMP-8 induced successful differentiation of BMSCs. After overexpression of SDF-1, the proliferation and differentiation of BMSCs were increased. In animal experiments, the BBB score increased after overexpression of SDF-1.

Discussion: These findings suggest a potential therapeutic mechanism in which SDF-1 promotes spinal cord repair by modulating the BMP-8/FBN1 axis. The suppression of FBN1 appears to be a key step in enhancing BMSC function. Targeting this pathway could offer new strategies for regenerative treatment following SCI.

Conclusion: In acute spinal cord injury, SDF-1 enhances the differentiation of bone marrow mesenchymal stem cells induced by BMP-8 through the suppression of FBN1.

Introduction: Acute myeloid leukemia (AML) arises from the aberrant proliferation of white blood cells, red blood cells, or platelets. Various therapy modalities are available for individuals diagnosed with AML. While Cytarabine remains a standard treatment, exosomes, especially those derived from cord blood, have emerged as promising adjuncts. Exosomes are a specific kind of extracellular vesicles that have been identified as candidate biomolecules for the treatment of AML. The current study looked at how cord blood-derived exosomes affect the U937 cell lines compared to Cytarabine as a fundamental component of standard AML treatment.

Methods: The first stage involved processing umbilical cord blood and isolating the mononuclear cells, CB-MNCs. The exosomes were isolated and verified using transmission electron microscopy, western blotting, and dynamic light scattering. Subsequently, for 72 hours, the U937 cells were cultivated and exposed to the exosomes, Cytarabine, and a combination of both. Afterward, apoptosis was evaluated using flow cytometry. The activity of Caspase 3/7 was assessed using a special kit. The real-time PCR technique was used to evaluate the gene expression in the proliferation and apoptosis pathways. Finally, the activity of NF-κB and AMPK was assessed using western blotting.

Results: The flowcytometry analysis showed that the apoptosis rate of U937 cells after being exposed to CB-MNC exosomes, Cytarabine, and a mix of them was 19.60 (p < 0.05) %, 44.05 % (P < 0.0001), and 47.45 % (P < 0.0001), respectively. The activity of Caspase 3-7 was 0.32 mU/mL and 0.45 mU/mL (P < 0.001) Cytarabine and Mix groups. The qRT-PCR study revealed a notable upregulation of apoptotic genes and a downregulation of anti-apoptotic gene expression in the Mix group. Western blot analysis revealed a decrease in NF-κB phosphorylation in all treatment groups. In addition, the phosphorylation of AMPK increased in all treatment groups.

Discussion: The study evaluated the effects of CB-MNC-derived exosomes on U937 cells, both alone and in combination with Cytarabine. Results demonstrated that while exosomes induced moderate apoptosis, their combination with Cytarabine significantly enhanced cell death, increased Caspase 3/7 activity, and altered gene expression in favor of apoptosis. The treatment also inhibited NF-κB and activated AMPK signaling pathways.

Conclusion: In conclusion, our findings indicated that CB-MNCs-derived exosomes together with Cytarabine have a cooperative effect on U937 cells through increasing apoptosis rate and reducing the proliferation rate, and may serve as a promising adjunct in AML therapy.