Current stem cell research & therapy最新文献

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 has 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 (hESCs) 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 the D-gal-induced hESC-NSCs senescence model, transcriptome sequencing was performed and analysed by bioinformatics method, followed by verification using 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, involving 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 to investigating human NSCs aging and provide valuable data for understanding the underlying mechanisms of oxidative stress-induced aging.

Nanotechnology seems to provide solutions to the unresolved complications in skin tissue engineering. According to the broad function of nanoparticles, this review article is intended to build a perspective for future success in skin tissue engineering. In the present review, recent studies were reviewed, and essential benefits and challenging issues regarding the application of nanoparticles in skin tissue engineering were summarized. Previous studies indicated that nanoparticles can play essential roles in the improvement of engineered skin. Bio-inspired design of an engineered skin structure first needs to understand the native tissue and mimic that in laboratory conditions. Moreover, a fundamental comprehension of the nanoparticles and their related effects on the final structure can guide researchers in recruiting appropriate nanoparticles. Attention to essential details, including the designation of nanoparticle type according to the scaffold, how to prepare the nanoparticles, and what concentration to use, is critical for the application of nanoparticles to become a reality. In conclusion, nanoparticles were applied to promote scaffold characteristics and angiogenesis, improve cell behavior, provide antimicrobial conditions, and cell tracking.

Background: While there is no certain treatment for spinal cord injury (SCI), stem cellbased therapy may be an attractive alternative, but the survival and differentiation of cells in the host tissue are poor. Conditioned medium (CM) has several beneficial effects on cells.

Objective: In this meta-analysis study, we examined the effect of CM on SCI treatment.

Methods: After searching on MEDLINE, SCOPUS, EMBASE, and Web of Science, first and secondary screening were performed based on title, abstract, and full text. The data were extracted from the included studies, and meta-analysis was performed using STATA.14 software. A standardized mean difference (SMD) with a 95% confidence interval was used to report findings. Quality control and subgroup analysis were also performed.

Results: The results from 52 articles and 61 separate experiments showed that CM had a significantly strong effect on improving motor function after SCI (SMD = 2.58; 95% CI: 2.17 to 2.98; p < 0.001) and also analysis of data from 12 articles demonstrated that CM reduced the expression of GFAP marker (SMD = -4.16; p < 0.0001) compared to SCI group without any treatment. Subgroup analysis showed that treatment with CM of neural stem cells was better than CM of mesenchymal stem cells. It was more effective after a mild lesion than a moderate or severe one. The improvement was more pronounced with <4 weeks than >4 weeks follow-up.

Conclusion: CM had a significant effect in improving motor function after SCI, especially in cases of mild lesions. It has been observed that if CM originates from the neural stem cells, it has a more significant effect than mesenchymal cells.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system and is a leading cause of disability in young adults. Most therapeutic strategies are based on immunosuppressant effects. However, none of the drugs showed complete remission and may result in serious adverse events such as infection. Mesenchymal stem cells (MSCs) have gained much attention and are considered a potential therapeutic strategy owing to their immunomodulatory effects and neuroprotective functions. Experimental autoimmune encephalomyelitis (EAE), a classical animal model for MS, is widely used to explore the efficacy and mechanism of MSC transplantation. This review summarises the therapeutic mechanism of MSCs in the treatment of EAE, including the effects on immune cells (T cells, B cells, dendritic cells, natural killer cells) and central nervous system-resident cells (astroglia, microglia, oligodendrocytes, neurons) as well as various strategies to improve the efficacy of MSCs in the treatment of EAE. Additionally, we discuss the clinical application of MSCs for MS patients as well as the challenges and prospects of MSC transplantation.

Background: The heavy burden of cardiovascular diseases demands innovative therapeutic strategies dealing with cardiomyocyte loss. Cardiac Stem Cells (CSCs) are renewable cells in the myocardium with differentiation and endocrine functions. However, their functions are significantly inhibited in conditions of severe hypoxia or inflammation. The mechanism of hypoxia affecting CSCs is not clear. Interleukin-6 (IL-6) appears active in both hypoxic and inflammatory microenvironments. The aim of this study was to explore whether IL-6 is related to CSC apoptosis and autophagy under severe hypoxia.

Methods: In this study, rat CSCs were extracted by alternate digestion. The interaction of miR-98 and IL-6 mRNA was detected by the dual luciferase method, and qPCR was applied to confirm the effect of miR-98 on IL-6 expression. The effect of IL-6 on CSC apoptosis was measured by flow cytometry and the effect of IL-6 on CSC autophagy by transmission electron microscopy. The western blot method was applied to detect the effect of IL-6 on the expressions of proteins related to apoptosis and autophagy. ANOVA and Dunnett T3's test were employed in the statistical analysis. When p < 0.05, the difference was significant.

Results: Under severe hypoxia conditions, IL-6 increased CSC apoptosis and decreased p-STAT3 expression significantly. CSC apoptosis increased significantly after inhibition of the STAT3 signaling pathway under severe hypoxia. IL-6 could also significantly inhibit CSCs' autophagy and block their autophagy flow under severe hypoxic conditions. Meanwhile, it was confirmed that miR-98 had a binding site on IL-6 mRNA and miR-98 significantly inhibited IL-6 mRNA expression in CSCs under severe hypoxic conditions.

Conclusion: miR-98/IL-6/STAT3 has been found to be involved in the regulation of CSCs' apoptosis and autophagy under severe hypoxic conditions and there might be a mutual linkage between CSCs' apoptosis and their autophagy.

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.

Background: Burn injuries pose a significant health challenge, leading to intense physiological stress compared to other types of trauma. Myrtle has been traditionally used for treating various skin ailments, while mesenchymal stem cells (MSCs) have introduced innovative approaches for burn treatment. This study aimed to evaluate the impact of myrtle compared to MSCs on the healing of deep second-degree burns.

Methods: Fifty adult male albino rats were randomly divided into five groups: Group A served as the control, Group B received an excision burn without treatment, Group C was treated with topical myrtle paste, Group D received an intradermal injection of mesenchymal stem cells (MSCs), and Group E received both topical myrtle paste and intradermal MSC injection. Burn healing was assessed based on visible characteristics over 21 days. At the end of the treatment, skin samples were collected for biochemical analysis, histological examination using hematoxylin and eosin (H&E) staining, and VEGF concentration measurement via ELISA. Additionally, PCR analysis was conducted to assess the expression levels of COL1a1, COL3a1, TNF-α, and IL-6, providing insights into collagen production and inflammatory response.

Results: Gross evaluation and histopathological analysis indicated that Groups D and E exhibited complete skin regeneration compared to the burn group. VEGF analysis demonstrated enhanced angiogenesis in the treated groups. PCR analysis revealed upregulation of COL1a1 and COL3a1, along with downregulation of TNF-α and IL-6, suggesting reduced inflammation and improved skin healing.

Conclusion: The study demonstrated that both MSCs and myrtle contributed to significant burn healing. The combination of myrtle and MSCs (Group E) exhibited the most effective skin regeneration, likely due to enhanced collagen production, reduced inflammation, and improved angiogenesis. These findings suggest that combining traditional herbal treatments with stem cell therapy may offer a promising strategy for burn management.

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.