Stem Cell Research & Therapy最新文献

Lung cancer is the first leading cause of cancer death worldwide. oxysterol-binding protein-like 2 (OSBPL2), is a lipid transport protein regulating cholesterol homeostasis. Here, we clarified the previously unreported role of OSBPL2 in lung cancer stemness properties. We observed that OSBPL2 reduced cholesterol content by HPLC-MS. It inhibited the accumulation of lipid droplets (LDs) in lung cancer. OSBPL2-mediated lipid transportation significantly suppressed tumor sphere formation, stemness markers expression and in vivo tumorigenesis and tumor metastasis. In clinical specimens, we also demonstrated that OSBPL2 repressed the expression of Lung cancer stem-like cells (LCSCs) markers-ALDH1A1, CD133 and Nanog. The level of OSBPL2 was negatively correlated with malignant of lung cancer, such as tumor stage progression and lymph node metastasis. Taken together, these findings illustrated that OSBPL2-mediated lipid transportation inhibited the stemness and aggressiveness of lung cancer cells. OSBPL2 was a potential therapeutic target to develop novel cancer-preventive compound.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by disrupted epidermal barrier function, immune dysregulation, and persistent inflammation. Affecting both children and adults, AD significantly impairs quality of life due to its visible symptoms and associated psychosocial and economic burdens. Traditional treatments such as application of topical corticosteroids, calcineurin inhibitors, moisturizers and antibiotics, while managing symptoms, often fall short of providing long-term solutions and can lead to adverse effects over time. This review explores innovative approaches to AD management, focusing on the therapeutic potential of the secretome. The secretome, a collection of bioactive molecules secreted by cells, has shown promise in promoting tissue regeneration and modulating immune responses. This study investigates how secretome therapy can restore the integrity of keratinocytes, the primary cells responsible for maintaining the skin barrier, which is severely compromised in AD. Using in vitro AD models, the secretome's potential to reduce inflammation and enhance skin barrier function is evaluated. By targeting the underlying mechanisms of AD, secretome-based therapies could offer a novel approach to treatment, providing both regenerative and anti-inflammatory benefits. The findings from this study may pave the way for more effective, non-invasive treatments that address the root causes of AD, potentially reducing the disease's impact and improving patient outcomes.

Background: Neurotmesis, remains a significant clinical challenge due to limited intrinsic regenerative capacity and suboptimal outcomes of current therapies. Mesenchymal stromal cells (MSCs) secretome has emerged as a promising cell-free alternative, providing neurotrophic and immunomodulatory factors to support nerve repair. This study aimed to evaluate the regenerative efficacy of primed adipose-derived MSC secretome in a rat model of sciatic nerve neurotmesis.

Methods: Human and rat adipose-derived MSCs were cultured and primed under hypoxic and inflammatory conditions. Secretomes were characterized by nanoparticle tracking analysis, proteomics, and total protein quantification. Neurotmesis was induced in Wistar rats, followed by repair with biomaterial alone or combined with human or rat secretome. Functional recovery was assessed by neurophysiological measurements at 6 months. Molecular and morphological regeneration was evaluated.

Results: Secretome priming enhanced the secretion of neurotrophic factors and immunomodulatory proteins, as confirmed by transcriptomic and proteomic analyses. In vivo, secretome-treated groups showed significantly improved neurophysiological recovery and increased NGF levels. qPCR revealed upregulation of myelination-associated genes in treated nerves. Histological and TEM analyses demonstrated robust axonal regeneration.

Conclusions: Primed MSC secretome markedly enhances structural and functional recovery after sciatic nerve neurotmesis, supporting its potential as a safe, effective, and scalable cell-free therapy for peripheral nerve repair.

Background: Human basal stem cells, with their self-renewal and multilineage differentiation capacity, are essential tools for modeling airway diseases and advancing regenerative medicine. However, existing culture systems often rely on undefined components like serum, bovine pituitary extract, or feeder cells, limiting reproducibility and clinical translation. To address this limitation, we developed a well-defined culture medium that enables the long-term expansion of human airway basal stem cells while preserving their proliferative and differentiation potential.

Methods: We formulated a novel medium (sfBSC) comprising 14 defined components, including basal media, supplements, growth factors (EGF, FGF10), and signaling inhibitors (Y-27632, A-83-01, DAPT, DMH1). Human bronchial and small airway epithelial cells were cultured over multiple passages in sfBSC and assessed for morphology, population doublings, marker expression, and differentiation capacity via air-liquid interface and organoid cultures. RNA-seq was performed to explore molecular changes across passages.

Results: Bronchial and small airway epithelial cells were expanded up to 17 and 24 passages, respectively, with stable morphology and consistent cell size (10-15 μm). Cells maintained expression of canonical BSC markers (TP63, KRT5, NGFR) throughout long-term culture. Differentiation assays confirmed the ability to generate ciliated, goblet, and club cells. Optimized concentrations of EGF (1 ng/mL) and FGF10 (0.4 ng/mL) were critical for sustained proliferation. RNA-seq revealed stable marker expression and metabolic changes over time.

Conclusions: sfBSC medium offers a defined, reproducible, and scalable platform for basal stem cell culture, enabling applications in disease modeling, regenerative medicine, and clinical-grade cell production.

Background: Endothelial cells (ECs) are crucial for tissue repair and wound healing but are prone to damage and apoptosis. When tissues or blood vessels are injured, endothelial progenitor cells (EPCs) are quickly activated, home to the site, and differentiate into ECs for endothelial integrity restoration. Apoptotic extracellular vesicles (Apo-EVs), released during apoptosis, have been found to regulate the micro environment, mediate intercellular communication, and participate in tissue repair, yet there's a lack of research on how EC-derived Apo-EVs, as intercellular communication media-tors, regulate EPCs' differentiation into ECs and promote angiogenesis and wound re-pair. Therefore, this study aims to explore whether EC-derived Apo-EVs can promote the differentiation of EPCs into ECs, facilitating wound angiogenesis, and to deeply analyze the underlying molecular mechanisms and key signaling pathways.

Methods: Human embryonic stem cells were differentiated into endothelial progenitor cells (EPCs) and endothelial cells (ECs), followed by phenotypic characterization. ECs were induced to undergo apoptosis for isolating EC-derived apoptotic extracellular vesicles (EC-Apo-EVs), which were co-cultured with EPCs to evaluate their pro-differentiation capacity. Integrative analysis of EPC transcriptome and EC-Apo-EV miRNA sequencing identified key mediating miRNAs and signaling pathways, validated in vitro. A murine skin wound model was established (randomized into control, EC-Apo-EV, and positive control groups) to assess EC-Apo-EVs' therapeutic efficacy in wound healing.

Results: In this study, we induced ECs apoptosis, extracted Apo-EVs for promoting angiogenesis and wound repair. The isolated Apo-EVs showed excellent ability to promote EPCs differentiation and angiogenesis in vitro and in vivo. In wound healing, Apo-EVs outperformed the positive control group. Mechanistically, miR-30a-5p in Apo-EVs inhibits Promyelocytic Leukemia (PML), activating the Epidermal Growth Factor Receptor/Phosphatidylinositol 3-Kinase/Protein Kinase B/Vascular Endothelial Growth Factor (EGFR/PI3K/AKT/VEGF) pathway in EPCs and exerting biological effects.

Conclusion: EC-derived Apo-EVs demonstrated excellent capacity to promote EPCs differentiation and angiogenesis both in vitro and in vivo, the mechanism is associated with miR-30a-5p within the vesicles inhibiting PML and activating the EGFR/PI3K/AKT/VEGF signaling pathway. This finding provides a new perspective for revealing the role of EC-derived Apo-EVs in tissue repair and offers potential strategies for the treatment of related diseases.

Adipose tissue-derived stromal vascular fraction (SVF) has rapidly emerged as a promising tool in regenerative medicine due to its accessibility, autologous origin, and potent reparative potential. However, despite encouraging preclinical outcomes, the clinical safety of SVF across organ systems remains insufficiently characterized. This comprehensive review synthesizes current evidence on the safety and tolerability of autologous SVF therapy in humans, organized by target organ systems including cardiovascular, pulmonary, hepatic, renal, musculoskeletal, cutaneous, neurological, and inflammatory applications. Across studies, SVF therapy appears technically feasible and generally well tolerated, with adverse events predominantly mild and procedure-related (e.g., transient pain, swelling, or local inflammation). Serious complications - including embolism, infection, fibrosis, or tumor formation - have not been reported to date in clinical settings. However, available studies suffer from major limitations: small and heterogeneous cohorts, non-randomized designs, variability in cell preparation and dosing, and short follow-up durations. The lack of standardized isolation protocols and absence of mechanistic endpoints further restrict interpretation. Overall, current data support the short-term safety of autologous SVF therapy, while underscoring the need for large-scale randomized controlled trials, harmonized methodologies, and long-term surveillance to fully establish its risk-benefit profile.

Background: Hair follicle stem cells (HFSCs) in androgenetic alopecia (AGA) patients exhibit functional impairment, reduced quantity, dysregulation, and androgen sensitivity, which hinder therapeutic strategies targeting HFSCs activation for hair regeneration. This study aims to elucidate the molecular mechanisms underlying HFSCs dysfunction in AGA and identify novel therapeutic targets.

Methods: We compared the expression of insulin-like growth factor 1 (IGF-1) in hair follicle tissues between AGA patients and healthy controls, analyzing transcriptional and protein-level differences. Bioinformatics, luciferase assays, and correlation analyses were employed to investigate the AR/miR-128-3p/IGF-1 pathway. Mechanistic studies were conducted using dermal papilla cells (DPCs) from both AGA patients and normal donors, which included RNA interaction assays and functional validation. Furthermore, the mechanism was validated by assessing the phenotypic changes in HFSCs co-cultured experiments. In vivo experiments in AGA mice were performed to evaluate hair follicle regeneration following ASLNC168501 overexpression.

Results: IGF-1 expression was markedly reduced in hair follicles of AGA patients, with transcriptional alterations occurring later than changes at the protein-level alterations. Dysregulation of the AR/miR-128-3p/IGF-1 pathway in DPCs was identified as a key driver of HFSCs dysfunction: AR transcriptionally activates miR-128-3p, which in turn suppresses IGF-1 by binding to its 3'UTR. Consequently, the ability of IGF-1 to sustain and support HFSCs activity is impaired. The endogenous ASLNC168501 functions as a ceRNA, sequestering miR-128-3p and thereby restoring IGF-1 expression and secretion. Exogenous overexpression of ASLNC168501 in DPCs significantly promoted the self-renewal, proliferative and differentiation potential of co-cultured HFSCs in vitro and reversed hair follicle atrophy in AGA mice.

Conclusions: Our findings demonstrate that loss of ASLNC168501 accelerates the progression of AGA by activating AR/miR-128-3p/IGF-1 pathway activation. Acting as a pathway-independent RNA, ASLNC168501 holds a target significant therapeutic potential for restoring HFSCs function and promoting hair follicle regeneration. This finding highlights a novel molecular target and contributes to the advancement of precision medicine strategies for androgen-related alopecia.

Stem cell therapy represents an emerging intervention for pulmonary fibrosis (PF), a severe lung disease lacking effective treatments. We conducted a systematic retrospective review of stem cell clinical trials for PF registered up to the end of 2024, utilizing the Trialtrove database alongside other registries.

Background: Acute lung injury/Acute respiratory distress syndrome (ALI/ARDS) is a life-threatening inflammatory lung disorder characterized by high mortality rates and a lack of effective treatment options. Although mesenchymal stem cell (MSC)-based therapies have emerged as a promising approach for ARDS management, optimizing their therapeutic efficacy remains a significant challenge. Recent advances in gene modification techniques have opened new avenues for enhancing MSC functionality. Among these, Fibronectin type III domain-containing protein 5 (Fndc5)/irisin has attracted considerable attention due to its ability to improve endothelial function. This study aims to evaluate the therapeutic potential of Fndc5-modified MSCs in sepsis-induced ALI/ARDS and to elucidate the underlying molecular mechanisms driving their protective effects.

Methods: To comprehensively evaluate the therapeutic potential of Fndc5-modified MSCs (MSCs-Fndc5) in ARDS, we employed both in vivo and in vitro experimental models. In vivo, a mouse model of sepsis-induced ALI was established through intraperitoneal injection of lipopolysaccharide (LPS), and the protective effects of MSCs-Fndc5 were systematically assessed by analyzing lung histopathology, inflammatory cytokine levels, vascular endothelial integrity, lung wet-to-dry weight ratio, and MSC retention in lung tissue. In parallel, in vitro studies were conducted to investigate the role of MSCs-Fndc5 in mitigating LPS-induced endothelial cell (EC) injury, with a focus on EC proliferation, angiogenesis, barrier permeability, apoptosis, and the regulation of key signaling pathways.

Results: Fndc5 modification significantly increased the retention rate of MSCs in sepsis-induced ALI murine model while augmenting their in vitro proliferation and migration potential. In vivo, treatment with Fndc5-modified MSCs markedly attenuated lung inflammation, as evidenced by reduced levels of pro-inflammatory cytokines, decreased neutrophil infiltration, and improved lung histopathology. Additionally, MSCs-Fndc5 alleviated pulmonary edema, reduced fibrosis, lowered the lung wet-to-dry weight ratio, and preserved vascular endothelial integrity. In vitro, MSCs-Fndc5 significantly enhanced cell proliferation, migration, angiogenesis, endothelial barrier function, apoptosis inhibition, likely via PI3K/AKT pathway activation.

Conclusions: Fndc5 overexpression in MSCs augments their therapeutic efficacy in sepsis-induced ALI/ARDS, which may be achieved by activating the endothelial PI3K/AKT pathway and improving MSCs retention in vivo. These findings propose MSCs-Fndc5 as a promising therapeutic strategy for sepsis-induced ALI/ARDS by enhancing endothelial repair, curbing inflammation, and modulating pivotal signaling pathways. Further investigation is warranted to explore the clinical applicability of MSCs-Fndc5 therapy for ARDS.