Stem Cells International最新文献

Skin aging is a multifaceted biological process driven by genetic and environmental factors, in which epidermal stem cells (EpSCs) decrease in number and decline in function. Emerging evidence indicates that epigenetic modifications play a crucial regulatory role in the aging process. Therefore, elucidating the epigenetic mechanisms in aging will provide novel avenues for developing strategies to delay aging. In this review, we explore the epigenetic mechanisms regulating EpSCs function, namely DNA methylation (DNAm), histone modifications, noncoding RNA, and their dysregulation and the resulting series of manifestations during aging. Furthermore, we introduce epigenetic clocks such as Horvath's and the skin-specific VisAgeX to quantify these age-related changes, which provide precise biomarkers of biological age, enabling the assessment of both aging progression and therapeutic outcomes. Finally, we summarize emerging interventions targeting these epigenetic disruptions. Advancing these epigenetic modulations holds significant potential for cutaneous antiaging and fostering innovative dermatological treatments.

Apoptotic vesicles (ApoVs) have garnered considerable attention within the realm of tissue regeneration research, necessitating a comprehensive bibliometric analysis to delineate current international trends and to map out historical and contemporary developments in this domain.

Methods: This study conducted a bibliometric analysis leveraging data sourced from the SCI-Expanded Web of Science (WOS) database. The analysis encompassed publications from October 1, 1991, to December 31, 2023. A total of 1209 articles focusing on ApoVs for tissue regeneration were scrutinized, considering attributes such as publication year, journal, author, institution, country/region, references, and keywords. Coauthorship, cocitation, co-occurrence analyses, network visualizations were generated using VOSviewer and CiteSpace.

Results: The analysis indicated a steady annual rise in global publications pertaining to ApoVs for tissue regeneration. The United States emerged as the foremost contributor, with the highest citation count and H-index. Furthermore, University of Tehran Medical Sciences was pinpointed as the most prolific institution. The journal International Journal of Molecular Sciences issued the largest account of articles on this topic. Notable subtopics such as "regenerative medicine," "delivery," and "mesenchymal stem cells" are poised to become significant research focal points in the near future.

Conclusions: Over the past 30 years, research on ApoVs for tissue regeneration has witnessed substantial growth, mirroring increasing collaboration across various countries and institutions. This study illuminates trends, collaboration patterns, research hotspots, and future trajectories in the field, providing valuable insights for researchers and practitioners.

Background: Periodontitis refers to a chronic inflammatory illness that induces the destruction of periodontal tissues and can be driven by bacterial lipopolysaccharide (LPS) of pathogens. This study investigated the anti-inflammatory potential and underlying mechanisms of ferulic acid (FA) in periodontitis.

Method: An in vitro periodontitis model was established by treating human periodontal ligament stem cells (hPDLSCs) with 10 µg/mL LPS for 24 h. The experimental groups included a control group, an LPS-treated group, and an LPS + FA cotreatment group. In addition, phorbol 12-myristate 13-acetate (PMA) treatment was used for nuclear factor κB (NF-κB) pathway activation. Cell proliferation was evaluated using the Cell Counting Kit-8 (CCK-8) test, and osteogenic differentiation was measured by alkaline phosphatase (ALP) and alizarin red S (ARS) staining. Apoptosis was detected with flow cytometry utilizing Annexin V-APC/PI double staining. Protein expressions were measured by Western blot. Inflammatory cytokine secretion was measured via enzyme-linked immunosorbent assay (ELISA) kits.

Result: This study uncovered that FA alleviates LPS-induced inflammatory responses in hPDLSCs, promoting cell proliferation and osteogenic differentiation. FA inhibits NF-κB pathway activation, reduces proinflammatory cytokines (tumor necrosis factor-alpha [TNF-α], interleukin [IL]-1β, IL-6), increases anti-inflammatory cytokine IL-10, and upregulates osteogenic markers (runt-related transcription factor 2 [Runx2], type I collagen [COL1], osteopontin [OPN], osteocalcin [OCN]). However, the protective effects of FA are reversed by the NF-κB activator PMA, indicating that its therapeutic efficacy primarily depends on NF-κB signaling regulation.

Conclusion: This study evaluated FA's effects on inflammation and osteogenic function in LPS-induced hPDLSCs, revealing its potential to alleviate periodontitis via NF-κB pathway inhibition and identifying a possible therapeutic target for periodontal disease.

Background: Glioblastoma (GBM) is the most common and aggressive malignant neoplasm in the central nervous system. Apoptosis is crucial in the genesis, progression, and management of tumors. Nevertheless, the influence of apoptosis-associated genes on GBM prognosis is unclear.

Methods: Transcriptome data and single-cell sequencing data were obtained from TCGA, CGGA, and GEO databases. Differential genes related to apoptosis were screened using the limma software, and an apoptosis-related gene prognostic model (apoptosis signature [AS] model) was constructed through univariate Cox analysis under the optimization of 101 machine learning algorithm combinations. Validation analyses were conducted using bioinformatics tools.

Results: A notable divergence in the expression levels of genes associated with programed cell death was identified when comparing GBM neoplastic tissues to their surrounding non-neoplastic counterparts. They were closely related to the prognosis of GBM patients. BRCA1, CHEK2, and IKBKE genes exhibited elevated levels of expression within neoplastic tissues and were identified as risk factors for prognosis, while ZMYND11, MAPK8, and RPS3 genes were highly expressed in adjacent nontumor tissues as protective factors. The AS model demonstrated good predictive performance across multiple datasets, showing a higher concordance index (C-index) value compared to conventional indicators of outcome. Moreover, the correlation coefficient between HSPB1 and the risk score associated with the AS model was positive, with a value of 0.75 (p < 2.2e-16).

Conclusions: An apoptosis-related gene prognostic model (AS model) with high predictive performance was constructed and had close associations with the tumor immune microenvironment and intercellular communication. The HSPB1 had a good predictive effect on GBM prognosis.

[This corrects the article DOI: 10.1155/2023/1662182.].

Background: In recent years, the incidence rates of type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) have increased significantly. Currently developed therapeutic approaches (e.g., pharmacotherapy) exhibit limited efficacy in the treatment of T2DM and OA, failing to fully restore joint function and pancreatic islet function. Mesenchymal stem cells (MSCs) have demonstrated substantial potential in repairing cartilage damage, reducing blood glucose levels, and other related aspects.

Objective: This review aims to evaluate whether MSC therapy represents a potential therapeutic strategy for T2DM complicated with OA.

Summary: This review highlights the association between OA and T2DM and summarizes the applications of MSCs in the treatment of OA and T2DM, the potential mechanisms of MSCs, as well as relevant therapeutic strategies.

Conclusion: MSC therapy may exert therapeutic effects in models of T2DM complicated with OA. This approach is expected to serve as an innovative and effective therapeutic method, promoting research on stromal cells and their applications. However, further studies are still required to verify its safety and feasibility.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease that significantly impacts quality of life. Reducing inflammation and restoring the skin barrier are key to its management.

Objective: This study aimed to investigate the protective and therapeutic effects of secretory substances from induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) in AD.

Methods: The protective effects of iMSC secretome pretreatment were evaluated in HaCaT cells by assessing cell viability, AD biomarker expression, and cell migration. Therapeutic efficacy was examined in a 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD mouse model through clinical, histological, and immunological assessments. Proteomic analyses were performed to relevant biological processes.

Results: iMSC secretome significantly reduced AD-induced cell death and AD biomarker expressions in vitro (p  < 0.05), with 200 μg/mL iMSC secretome promoting cell migration. In vivo, high dose (20 mg/mL) iMSC secretome alleviate clinical indicators compared to the vehicle group (p  < 0.05). Serum immunoglobulin (Ig) E, interleukin (IL)-4, IL-31, and IL-6 levels, along with the expression of AD biomarkers in skin, were significantly decreased (p  < 0.05). Proteomic analyses revealed upregulation of genes involved in the regulation of immune responses and the restoration of skin barrier.

Conclusion: iMSC secretome demonstrates significant anti-inflammatory and regenerative effects, making it a promising therapeutic option for AD.

Background: Protein kinase R-like endoplasmic reticulum kinase (PERK) mediates the endoplasmic reticulum stress (ERS) response. However, it remains unclear whether PERK regulates the odontogenic differentiation of human dental pulp stem cells (hDPSCs) and contributes to the repair and regeneration of the pulpo-dentinal complex (PDC) during inflammation. This study aimed to investigate the regulation of ERS-PERK in the differentiation and apoptosis of hDPSCs and its contribution to the repair and regeneration of PDC injury in the inflammatory microenvironment.

Methods: In vivo dentin defect (DD group) and pulp perforation (PP group) were established to evaluate the expression and healing-promoting properties of PERK in dental pulp at different injury stages. Using LPS with concentration gradients to simulate the inflammatory microenvironment, the activation of ERS-PERK pathway-related genes was investigated using quantitative real-time polymerase chain reaction (RT-qPCR). hDPSCs' apoptosis and odontogenic potential under inflammatory stimulation were also assessed using Calcein-AM/7AAD Live/Dead cell double staining, RT-qPCR, alkaline phosphatase (ALP) staining, and Alizarin Red S (ARS) staining. The potential role of PERK in odontogenesis and apoptosis of hDPSCs under inflammatory stimulation was explored.

Results: With the extension of dental defects in vivo, PERK expression was gradually upregulated in the DD group, whereas, in the PP group, it increased in the early stage of inflammation and then decreased. Under LPS stimulation, the expression of inflammatory factors increased with the activation of the PERK pathway, while the ALP activity of hDPSCs and mineralized nodules decreased. PERK knockdown attenuated mRNA levels of ERS-related genes and apoptosis-related genes, whereas the expression of odontogenic-related factors increased. The ALP activity and the number of mineralized nodules increased. PERK may regulate odontogenesis through the mitochondria-associated endoplasmic reticulum (ER) membrane.

Conclusion: Our results demonstrated PERK pathway activation, which enhances the expression of inflammatory factors and suppresses the odontogenic ability of hDPSCs in inflammatory microenvironments.

Background: Hyperthermia is a widely used adjunct treatment for different cancers. The GLI1 is upregulated in ESCC and its expression is associated with the stemness of ESCC.

Objective: We hypothesized that GLI1 constitutes an important hyperthermia treatment target, and investigated its contribution to hyperthermia responses in ESCC.

Methods: The growth of the human ESCC cell lines KYSE70 and KYSE140 was analyzed using CCK-8, clonogenicity and spheres formation assays after 43°C hyperthermia, under conditions of knockdown or overexpression of GLI1. Stemness-related proteins were determined using Western blotting and immunofluorescence staining. Last, the molecular mechanism of GLI1 degradation was studied using chemical inhibitors and immunoprecipitation assays.

Results: Hyperthermia increased the ubiquitination and proteasomal destruction of GLI1, causing a rapid decline in GLI1 protein levels of ESCC cells. Similar to GLI1 knockdown, ESCC cells treated with hyperthermia showed growth inhibition associated with the downregulation of cancer stemness proteins.

Conclusion: Our study reveals that hyperthermia can readily destabilize GLI1 levels in ESCC cells and inhibit ESCC cells growth. This proposes new strategies for implementing hyperthermia to target GLI1 driven cancers to improve therapeutic efficacy.

Objective: This study aimed to investigate the effect of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway inhibition on D-galactose (D-gal)-induced senescence in nucleus pulposus cells (NPCs) and its potential to delay intervertebral disc degeneration (IVDD), as well as to investigate the underlying mechanisms.

Methods: A cellular senescence model was established by treating rat NPCs with D-gal. The model was then intervened with a JAK2/STAT3 pathway inhibitor (ruxolitinib) or JAK2-specific small interfering RNA (siRNA). Cellular senescence was evaluated by senescence-associated β-galactosidase (SA-β-gal) staining. The expression of senescence markers (p16, p21, and p53), extracellular matrix (ECM) components (aggrecan and collagen II), catabolic enzymes (ADAMTS-4, ADAMTS-5, MMP-3, and MMP-13), and JAK2/STAT3 pathway proteins was analyzed by western blotting and immunofluorescence. The levels of inflammatory factors (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α [TNF-α]) and advanced glycation end-products (AGEs) were measured by enzyme-linked immunosorbent assay (ELISA). Cell proliferation, apoptosis, and cell cycle distribution were assessed using cell counting kit-8 (CCK-8) and flow cytometry. In a parallel in vivo study, a rat model of IVDD was induced by D-gal and treated with the JAK inhibitor. Disc degeneration was evaluated by magnetic resonance imaging (MRI) and histopathological examination after 8 weeks.

Results: Both in vitro and in vivo, inhibition of the JAK2/STAT3 pathway, either pharmacologically or genetically, effectively attenuated D-gal-induced effects. It suppressed the phosphorylation of STAT3, reduced the expression of SA proteins (p16, p21, and p53), ECM catabolic enzymes (ADAMTS-4, ADAMTS-5, MMP-3, and MMP-13), and proinflammatory cytokines (IL-1β and IL-6). Consequently, this inhibition decreased SA-β-gal positivity, alleviated cell cycle arrest and apoptosis, and enhanced the synthesis of aggrecan and collagen II in NPCs. In the rat model, JAK inhibitor treatment improved MRI scores, restored disc signal intensity, and ameliorated histopathological degeneration.

Conclusion: : Inhibition of the JAK2/STAT3 pathway reduced the expression of inflammatory factors and oxidative stress markers in D-gal-treated NPCs. It also suppressed ECM degradation and apoptosis, delayed cellular senescence, and attenuated the progression of IVDD in rats.