Current stem cell research & therapy最新文献

Background: This study aimed to assess the knowledge, perception, and willingness of the Saudi population towards stem cell treatment and banking, the associated factors, and their predictive abilities.

Methods: A cross-sectional study was conducted from September to December 2022 in Saudi Arabia using a structured bilingual, self-administered online survey to collect sociodemographic information and determine the knowledge and understanding, perception, and willingness of the general population. Bloom's cut-off points were used to distribute the scores into three categories, namely strong (80-100%), moderate (60-79%), and weak (<59%). Descriptive statistics were used to assess each domain, while t-tests, ANOVA, and binary logistic regression were used to assess factors influencing each domain and their predictive abilities.

Results: The study conscripted 440 respondents, mainly females (70%) aged 18-24 years (56.1%), mostly single (44.3%), Saudi nationals (89%), and college graduates (56.6%). Social media (53.4%) was the primary source of information. 77.95% of respondents exhibited a low level of knowledge. Females, Saudi nationals, respondents with Islamic beliefs, college graduates, and those who received information from family physicians and social media had significantly better knowledge. 50.68% of respondents showed a strong perception. Non-Saudi participants, those who received information from family and friends, and respondents with a high prevalence of hypertension and diabetes in their families had a better perception. However, only 21.59% showed strong willingness toward stem cell treatment and banking, including Saudi nationals and college graduates. Gender was found to be a significant predictor for better knowledge and perception, while no sociodemographic variables significantly predicted willingness.

Conclusion: This study emphasizes the need for increased awareness, educational campaigns, and targeted strategies considering various socio-demographic factors to improve the knowledge, perception, and willingness of the general population toward stem cell treatments and banking in Saudi Arabia.

Introduction: Neural stem cells (NSCs) are vulnerable to oxidative stress, which triggers aging and subsequently leads to a reduced regenerative capacity of the central nervous system (CNS). Due to the challenges in acquiring aged human NSCs and the lack of an oxidative stressinduced aging model specifically designed for human NSCs, research related to the aging mechanisms and the screening of anti-aging drugs have been limited. Here, we aimed to establish an oxidative stress-induced senescence model of NSCs by using D-galactose (D-gal).

Methods: Human embryonic stem cells (hESC) were differentiated into hESC-NSCs using a type I collagen method. hESC-NSCs were characterized by flow cytometry combined with immunofluorescence. A senescence model of hESC-NSCs was established using D-gal and characterized by CCK-8 assay, neurosphere formation, crystal violet staining, DNA damage assay, SA-β-gal staining and ROS levels measurement. To further explore the profile of gene expression in D-gal-induced hESCNSCs senescence model, transcriptome sequencing was performed and analysed by bioinformatics method, following verified by qPCR.

Results: The hESC-derived NSCs senescence model demonstrated reduced proliferation and elevated β-galactosidase activity, accompanied by DNA damage and increased levels of reactive oxygen species. Furthermore, transcriptome analysis unveiled the potential central role of the MAPK signaling pathway in D-gal-induced senescence, which involves the key genes including DDIT3, ATF3, CEBPB, JUN, and CCND1.

Conclusion: We presented an oxidative stress-induced senescence model of hESC-NSCs and identified key pathways and genes related to D-gal-induced senescence. Our study might offer an alternative approach for investigating human NSC aging and provide valuable data for understanding the underlining mechanisms of oxidative stress-induced aging.

Tissue homeostasis and regeneration depend on differentiated stem cells into specialized cell types. Dietary interventions, such as caloric restriction, are critical regulators of stem cell functions by altering their metabolism. This review discusses recent studies illustrating how diet interventions impact stem cell function. We summarize molecular targets and physiological effects of different types of caloric restriction and ketogenic mimicking diets in stem cells from bone marrow, muscle, and intestine. Furthermore, we highlight the nutrient-sensing pathway target of stem cells during caloric restriction. Understanding how nutrient signaling controls stem cell fate decisions is important to developing dietary interventions to improve the clinical application of stem cells.

Background: Since there is currently no cure for amyotrophic lateral sclerosis (ALS), it is essential to search for diagnostic biomarkers and novel treatments to reduce the severity of this disease. One of these treatment approaches is stem cell transplantation.

Objective: This study aims to evaluate the safety and efficacy of repeated transplantation of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with ALS by analyzing clinical and molecular data.

Methods: This one-arm, single-center, open-label without a control group, prospective clinical trial, twenty-one confirmed ALS patients entered the study based on defined inclusion and exclusion criteria and underwent repeated stem cell transplantation (3 times BM-MSCs transplantation (1×10^6, MSC/Kg BW per injection) concurrently intrathecally (IT) and intravenously (IV), with one-month interval). Clinical assessment using ALS functional rating scale-revised (ALSFRS) and forced vital capacity (FVC) values and also molecular investigation by evaluating specific microRNAs expression (mir206, 133a-3p, 338-3p) in patient's serum and Cerebra spinal fluid (CSF) samples were done three times during the 3-month follow-up period.

Result: No serious adverse effects were reported during the study. Besides, significant improvement in FVC when compared the baseline with the end of the research and the p-value was (0.036), and stability in ALSFRS was observed, and the p-value was (p=0.16) following stem cell transplantation in patients; also, the mentioned microRNA expression was non-significant (p > 0.05) as reported as well.

Conclusion: Our results demonstrated that repeated transplantation of BM-MSCs was a safe procedure in ALS patients, leading to delay in disease progression and improvement in clinical symptoms. Future studies are needed to confirm these results.

Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach in the treatment of brain cancer due to their unique biological properties, including their ability to home tumor sites, modulate the tumor microenvironment, and exert anti-tumor effects. This review delves into the molecular mechanisms and pathways underlying MSC-mediated therapy in brain cancer. We explore the various signalling pathways activated by MSCs that contribute to their therapeutic efficacy, such as the PI3K/Akt, Wnt/β-catenin, and Notch pathways. Additionally, we discuss the role of exosomes and microRNAs secreted by MSCs in mediating anti-tumor effects. The review also addresses the challenges and future directions in optimizing MSC-based therapies for brain cancer, including issues related to MSC sourcing, delivery methods, and potential side effects. Through a comprehensive understanding of these mechanisms and pathways, we aim to highlight the potential of MSCs as a viable therapeutic option for brain cancer and to guide future research in this field.

Introduction: Osteoarthritis (OA) is a degenerative joint disease that can affect the many tissues of the joint. There are no officially recognized disease-modifying therapies for clinical use at this time probably due to a lack of complete comprehension of the pathogenesis of the disease. In recent years, emerging regenerative therapy and treatments with stem cells both undifferentiated and differentiated cells have gained much attention as they can efficiently promote tissue repair and regeneration.

Methods: To determine how bone marrow-derived mesenchymal stem cells (BM-MSCs) and chondrogenic differentiated MSCs (CD-MSCs) can treat OA in rats, OA was induced in Wistar rats by injecting three doses of 100 μL physiological saline containing 1 mg of MIA into rat ankle joint of the right hind leg for three consecutive days. Following the induction, the osteoarthritic rats were injected weekly with BM-MSCs or CD-MSCs at a dose of 1x106 cells/rat/dose for three weeks. In addition to morphological and histological investigations of the ankle, spectrophotometric, ELISA, and Western blot analyses were applied to detect various immunological and molecular parameters in serum and ankle.

Results: The results of the study showed that in osteoarthritic rats, BM-MSCs and CD-MSCs significantly reduced right hind paw circumference, total leucocyte count (TLC), differential leukocyte count (DLC) of neutrophils, monocytes, lymphocytes, and eosinophils, serum rheumatoid factor (RF), prostaglandin E2 (PGE2) and interleukin (IL-) 1β levels, while they elevated serum IL-10 level. Additionally, BM-MSCs and CD-MSCs markedly reduced lipid peroxides (LPO) levels while they elevated superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities. The monocyte chemoattractant protein-1 (MCP-1) level was significantly downregulated in ankle joint articular tissues by treatment with BM-MSCs or CD-MSCs while nuclear factor erythroid 2-related factor 2 (Nrf2) was upregulated; CD-MSCs treatment was more effective.

Conclusion: According to these findings, it can be inferred that BM-MSCs and CD-MSCs have anti-arthritic potential in MIA-induced OA; CD-MSCs therapy is more effective than MSCs. The ameliorative anti-arthritic effects may be mediated by suppressing inflammation and oxidative stress through the downregulation of MCP-1 and upregulation of Nrf2. Based on the obtained results, BM-MSCs and CD-MSCs therapies are promising new options that can be associated with other clinical treatments to improve cartilage regeneration and joint healing. However, more preclinical and clinical research is required to assess the benefits and safety of treating osteoarthritic patients with BM-MSCs and CD-MSCs.

Objectives: The osteogenic potential of periodontal ligament stem cells (PDLSCs) is crucial for periodontal tissue regeneration. Prolonged and excessive oxidative stress (OS) impairs the osteogenic function of PDLSCs. Recently, Semaphorin 3A (Sema3A) has been reported to have multiple roles in bone protection. This study aimed to investigate the protective effect of Sema3A on the osteogenic differentiation of PDLSCs under OS conditions induced by hydrogen peroxide (H2O2).

Methods: PDLSCs were subjected to H2O2 treatment to induce OS. The OS indices in PDLSCs were evaluated by analyzing levels of reactive oxygen species (ROS), cell viability, and expression of antioxidant factors using relevant assay kits. A small molecule inhibitor, XAV-939, was employed to block the Wnt/β-catenin pathway. Osteogenic differentiation was assessed using alkaline phosphatase (ALP) activity staining and Alizarin Red S (ARS) staining for mineralized nodules. Expression levels of osteogenic gene markers and β-catenin were determined via real-time quantitative polymerase chain reaction (RT-qPCR) or western blot (WB) analysis.

Results: The stimulation of H2O2 induced OS in PDLSCs, resulting in a downregulation of Sema3A expression and a decrease in osteogenic markers, including ALP activity, mineralized nodule formation, and the expression of osteogenic genes (RUNX2 and ALP). However, the application of recombinant human Sema3A (rhSema3A) counteracted H2O2-induced OS and restored these osteogenic markers in PDLSCs under OS induced by H2O2. Mechanistic studies revealed that these effects were associated with an upregulation of β-catenin levels. Moreover, inhibiting β-- catenin expression compromised the protective effect of Sema3A on osteogenesis in PDLSCs under OS.

Conclusion: Sema3A exerts a protective effect against H2O2-induced OS and activates the Wnt/β-- catenin pathway to restore osteogenic differentiation impaired by OS in PDLSCs.

Vascular stents and stem cells have been used in high-acuity cases for many decades, particularly in cardiology. Providing the physician with another avenue of treatment, they have had a reasonable amount of success. However, there has been very little research conducted on seeding vascular stents with stem cells when treating intracranial aneurysms. Our work aims to understand the current literature available on the viability of such stents and the future directions one should take when choosing stents seeded with stem cells. Three computerized searches in PubMed were used. Four papers met the criteria, and two were excluded. There have been some experiments where the efficacy of vascular stents seeded with different materials was tested. G/PLL- coated stents provided multiple advantages and bioactive benefits to the mesenchymal stem cells. On the other hand, SF/SDF-1α also promoted similar benefits but provoked multiple unwanted inflammatory responses. G/PLL and SF/SDF-1α coated stents were able to provide satisfactory results but still require more extensive research to thoroughly understand their efficacies and safety. Future directions may include researching and discovering a wider array of biocompatible materials to seed the stents.

Single-cell technology (SCT), which enables the examination of the fundamental units comprising biological organs, tissues, and cells, has emerged as a powerful tool, particularly in the field of biology, with a profound impact on stem cell research. This innovative technology opens new pathways for acquiring cell-specific data and gaining insights into the molecular pathways governing organ function and biology. SCT is not only frequently used to explore rare and diverse cell types, including stem cells, but it also unveils the intricacies of cellular diversity and dynamics. This perspective, crucial for advancing stem cell research, facilitates non-invasive analyses of molecular dynamics and cellular functions over time. Despite numerous investigations into potential stem cell therapies for genetic disorders, degenerative conditions, and severe injuries, the number of approved stem cell-based treatments remains limited. This limitation is attributed to the various heterogeneities present among stem cell sources, hindering their widespread clinical utilization. Furthermore, stem cell research is intimately connected with cutting-edge technologies, such as microfluidic organoids, CRISPR technology, and cell/tissue engineering. Each strategy developed to overcome the constraints of stem cell research has the potential to significantly impact advanced stem cell therapies. Drawing on the advantages and progress achieved through SCT-based approaches, this study aims to provide an overview of the advancements and concepts associated with the utilization of SCT in stem cell research and its related fields.

Background: Cancer stem cells (CSC) play an important role in the development of Liver Hepatocellular Carcinoma (LIHC). However, the regulatory mechanisms between acetylation- associated genes (HAGs) and liver cancer stem cells remain unclear.

Objective: To identify a set of histone acetylation genes (HAGs) with close associations to liver cancer stem cells (LCSCs), and to construct a prognostic model that facilitates more accurate prognosis assessments for LIHC patients.

Methods: LIHC expression data were downloaded from the public databases. Using mRNA expression- based stemness indices (mRNAsi) inferred by One-Class Logistic Regression (OCLR), Differentially Expressed Genes (DEGs) (mRNAsi-High VS. mRNAsi-Low groups) were intersected with DEGs (LIHC VS. normal samples), as well as histone acetylation-associated genes (HAGs), to obtain mRNAsi-HAGs. A risk model was constructed employing the prognostic genes, which were acquired through univariate Cox and Least Shrinkage and Selection Operator (LASSO) regression analyses. Subsequently, independent prognostic factors were identified via univariate and multivariate Cox regression analyses and then a nomogram for prediction of LIHC survival was developed. Additionally, immune infiltration and drug sensitivity analysis were performed to explore the relationships between prognostic genes and immune cells. Finally, the expressions of selected mRNAsi-HAGs were validated in the LIHC tumor sphere by quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) assay and western blot analysis.

Results: Among 13 identified mRNAsi-HAGs, 3 prognostic genes (HDAC1, HDAC11, and HAT1) were selected to construct a risk model (mRNAsi-HAGs risk score = 0.02 * HDAC1 + 0.09 * HAT1 + 0.05 * HDAC11). T-stage, mRNAsi, and mRNAsi-HAGs risk scores were identified as independent prognostic factors to construct the nomogram, which was proved to predict the survival probability of LIHC patients effectively. We subsequently observed strongly positive correlations between mRNAsi-HAGs risk score and tumor-infiltrating T cells, B cells and macrophages/monocytes. Moreover, we found 8 drugs (Mitomycin C, IPA 3, FTI 277, Bleomycin, Tipifarnib, GSK 650394, AICAR and EHT 1864) had significant correlations with mRNAsi-HAGs risk scores. The expression of HDAC1 and HDAC11 was higher in CSC-like cells in the tumor sphere.

Conclusion: This study constructed a mRNAsi and HAGs-related prognostic model, which has implications for potential immunotherapy and drug treatment of LIHC.