Stem Cells International最新文献

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) ameliorate motor deficits in cerebral palsy (CP), but the effect of injection frequency remains unclear. Moreover, most studies have focused on mild CP models (unilateral carotid artery occlusion [UCAO] model). This study explored the effect and mechanism of hUC-MSCs in a rat model of moderate-to-severe CP (bilateral carotid artery occlusion [BCAO] model). On postnatal Day 4 (P4), Wistar rat pups underwent BCAO induction. Subsequently, they received either a single intrathecal injection of hUC-MSCs on P21 or repeated injections on P21, P28, P35, and P42. Motor performance was assessed using the rotarod and front-limb suspension tests, while neuronal regeneration and inflammation were evaluated via biomarkers including neuronal nuclear antigen (NeuN), ionized calcium-binding adapter molecule-1 (Iba-1), glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), and brain-derived neurotrophic factor (BDNF). P18 model screening confirmed that the BCAO model resulted in more severe brain damage and motor impairment than the UCAO model. After injection of lentivirally transfected hUC-MSCs, it was found that hUC-MSCs could nest in the damaged area and survive for at least 3 days. Administration of hUC-MSCs following BCAO modeling led to notable improvements in both behavioral performance and histological outcomes. Furthermore, repeated injections offered greater therapeutic benefits compared to single injection. It indicated that the efficacy of repeated injections of hUC-MSCs in the treatment of moderate-to-severe CP was superior to that of single injection. Its mechanism was related to the improvement of damaged myelin structure, reduced immunoinflammatory responses, and increased neurotrophic support.

Globally, stroke stands as a principal cause of death and disability, presenting formidable challenges in rehabilitation. Conventional therapeutic modalities often fail to restore functional capabilities fully, underscoring the need for innovative treatment strategies. Stem cell therapy emerges as a revolutionary approach, capitalizing on the regenerative capabilities of stem cells to improve neurological function poststroke. This review evaluates the roles of various stem cell types-mesenchymal stem cells (MSCs), neural stem cells (NSCs), and induced pluripotent stem cells (iPSCs)-in the realm of stroke recovery. It elucidates their distinct biological mechanisms, evaluates their therapeutic impact based on clinical trial data, and discusses their efficacy in fostering neural repair and recovery. MSCs are particularly noted for their role in immunomodulation and promotion of angiogenesis and neurogenesis, with clinical evidence supporting their safety and effectiveness in stroke recovery. NSCs are lauded for their ability to differentiate into diverse neural lineages. They integrate into neural circuits to enhance synaptic connectivity and neuroplasticity. iPSCs, known for their versatility, can be tailored to patient-specific needs and are shown in preclinical settings to reduce infarct size and promote the survival of neuronal cells. However, the field grapples with challenges, including optimizing stem cell transplantation timing, precision in cell delivery, integration efficiency, and immune system compatibility. These issues call for harmonization of methodologies across ongoing studies to ensure the reliability and consistency of therapeutic outcomes. This review highlights the promising future and challenges of stem cell therapy for treatment of stroke.

Repair of large soft tissue defects by tissue expansion often faces difficulties in skin expansion. Particularly in those who have lost a significant amount of skin and subcutaneous tissue due to total mastectomy, tissue expansion may result in skin breakdown and exposure of the expander. Subcutaneous fat construction by autologous fat grafting before expansion seems to assist skin expansion. We hypothesize that it may be related to the adipose-derived stem cells (ADSCs) in subcutaneous fat. In this study, we confirmed this phenomenon through animal experiments and provided a preliminary investigation of the possible mechanisms involved. Four groups were designed for the experiment, experimental group (EG) for autologous fat flap transfer and tissue expansion. Fat grafting control group (FGCG), where only autologous fat flap transfer was performed without tissue expansion. Tissue expansion control group (TECG) did not perform autologous fat flap transfer but only skin tissue expansion on the back. Blank control group (BCG) has not received any surgery. In each group of 20 rats, skin, and fat flaps of the dilated area were sampled at four time points (7, 14, 21, and 28 days, n = 5), and the immediate skin retraction rate of the expanded area in the EG and TECG groups was measured to evaluate the expansion effect. GFP⁺ADSCs were observed to demonstrate whether they were facilitated by tissue expansion and migrated from autologous fat flaps to skin. Our study supported that fat layer construction prior to skin expansion helps to promote skin growth. The promotion may be related to the migration of ADSCs from adipose to dermis by compression, and ADSCs migrating to dermis further promote skin stretching through direct differentiation or paracrine cytokines to promote cell proliferation and collagen synthesis.

Thoracic aortic dissection (TAD) is a life-threatening condition characterized by medial degeneration and vascular smooth muscle cell (VSMC) dysfunction, with no effective medical therapy currently available. The underlying pathological mechanisms of TAD remain incompletely understood. In this study, we used a nonintegrated episomal vector-based reprograming system to generate induced pluripotent stem cells (iPSCs) from TAD patients and healthy controls. Both TAD and normal iPSCs expressed key pluripotency markers and were capable of differentiating into the three germ layers in vitro. These iPSCs were differentiated into vascular smooth muscle cells (VSMCs) through a mesodermal intermediate for disease modeling. VSMCs derived from both TAD and normal iPSCs expressed smooth muscle α-actin (α-SMA), calponin (CNN), and SM22α. However, TAD-iPSC-derived VSMCs exhibited significantly reduced contraction in response to carbachol stimulation compared to their normal counterparts. Whole-exome sequencing identified a mutation in the COL4A2 gene (c.392G > T, p. R131M) in TAD-iPSCs. This mutation was associated with reduced collagen IV expression and increased expression of collagen I and III in TAD-VSMCs, both with and without TGF-β stimulation. Furthermore, noncanonical TGF-β signaling was hyperactivated in TAD-VSMCs, accompanied by elevated MMP9 expression. This patient-specific iPSC model reveals key dysfunctions in VSMC contractility, extracellular matrix (ECM) protein expression, and dysregulated TGF-β signaling, which may contribute to TAD pathogenesis. Our findings provide new insights into the molecular mechanisms driving TAD and offer a platform for future therapeutic development.

[This corrects the article DOI: 10.1155/sci/8681205.].

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.].