Stem Cells International最新文献

Oral potentially malignant disorders (OPMDs) have varying risk of malignant transformation (MT), yet the underlying mechanisms remain unclear. Recent evidence suggest emerging role of stem cells in carcinogenesis. This systematic review aimed to synthesizes current knowledge on the role of stem cells in OPMD and MT. Review protocol was developed in accordance with PRISMA 2020 guidelines and registered with PROSPERO. Literature searches identified 4882 records from PubMed, Scopus, Embase, and Web of Science databases; from these, n = 97 primary research studies were selected via two stage screening. Data extraction and narrative synthesis was conducted according to synthesis without meta-analysis (SWiM) guidelines. Methodological quality was assessed using Joanna Briggs Institute (JBI) critical appraisal checklists. Studies included in this review were published between 2006-2025, where majority of the research were from India and China. Immunohistochemistry (IHC) was used to identify stem cell biomarkers in tissue samples, most studies demonstrated that higher expression of stem cell markers (CD44, ALDH1, HELLS, TARIF, SOX2, NANOG, and CD147) correlated with severity of epithelial dysplasia. Longitudinal data identified ALDH1 and Bmi-1 as promising prognostic biomarkers linked to MT. Evidence from cell culture and animal model experiments suggested potential therapeutic applications of stem cells and their exosomes in haltering the progression of OPMD. Notably, a clinical trial incorporated stem cell markers as surrogate end points for evaluating treatment options. While findings underscore the prognostic and therapeutic relevance of stem cells in OPMD, lack of prospective designs in biomarker validation and absence of clinical trial evidence on stem cell therapies limit clinical applicability.

Purpose: To evaluate the effects of limbal mesenchymal stem cell secretome (LMSC-S) on corneal endothelial NF-κB, TNF-α, and Caspase-8 expression after U/S power injury of the phacoemulsification machine.

Setting: Stem Cell Research and Development Center, Universitas Airlangga.

Design: Experimental studies on laboratory animals.

Methods: The normal group included eight eyes of four rabbits, and the other groups each included seven eyes of seven rabbits. The normal group consisted of eyes without exposure or treatment. Control group 1 (C1) served as the control for treatment group 1 (T1), where LMSC-S was administered simultaneously with the U/S power exposure. Control group 2 (C2) served as the control for treatment group 2 (T2), in which LMSC-S was administered 3 days after U/S power exposure. Corneal endothelial cell (CEC) damage was induced by exposure to ultrasound from a phacoemulsification machine. Rabbit LMSC-S cells were obtained from the Stem Cell Research and Development Center, Universitas Airlangga. Expression of NF-κB, TNF-α, and Caspase-8 were assessed by immunohistochemistry (IHC).

Results: All studied cytokines increased after U/S power injury (NF-κB: p = 0.047 for N-C1; p < 0.001 for N-C2, TNF-α: p < 0.001 for N-C1 and N-C2, Caspase-8: p < 0.001 for N-C1 and N-C2). T2 group showed the least increase and was closer to normal (NF-κB: p = 0.002 for N-T1, p = 0.081 for N-T2; TNF-α: p = 0.005 for N-T1, p = 0.161 for N-T2; Caspase-8: p = 0.013 for N-T1, p = 0.739 for N-T2).

Conclusions: LMSC-S therapy on the third day postexposure decreased corneal endothelial apoptotic cytokine expression.

Background: Meniscal healing is often limited because adult meniscal fibrochondrocytes (MFCs) possess inherently low proliferative and reparative capacities. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have recently emerged as promising cell-free therapeutics with regenerative potential, whereas transforming growth factor-β1 (TGF-β1) is a well-established chondrogenic factor. In this study, we investigated the potential synergistic effects of BMSC-Exos and TGF-β1 on MFC proliferation, migration, and extracellular matrix synthesis in vitro.

Objective: To explore the effects of BMSC-Exos combined with TGF-β1 on MFCs and to investigate new approaches for treating meniscus injuries.

Methods: BMSC-Exos were extracted by differential centrifugation and identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting. The meniscus fibrochondrocytes were treated with BMSC-Exos, TGF-β1, and BMSC-Exos + TGF-β1 for 24 h. The distribution of fluorescently labeled BMSC-Exos in meniscus fibrochondrocytes was observed by fluorescence microscopy. The effects of BMSC-Exos, TGF-β1, and BMSC-Exos + TGF-β1 on the proliferation and migration of meniscus fibrochondrocytes were evaluated by CCK-8 assay, DNA quantification, cell migration assay, and cell scratch assay.

Results: (1) BMSC-Exos are crescent-shaped, with an average particle size of approximately 118 nm, and express the specific protein TSG101. (2) The results of immunofluorescence staining showed that BMSC-Exos were aggregated in the fibrocartilage cells of the meniscus. (3) Compared with the blank control group (CON group), the proliferation and migration abilities of the fibrocartilage cells of the meniscus in the three experimental groups were all enhanced, among which the BMSC-Exos + TGF-β1 group had the most significant effect. (4) The DNA content of the cells in the three experimental groups was all higher than that of the CON group, and the DNA content of the cells in the BMSC-Exos + TGF-β1 group was the highest (p < 0.001).

Conclusion: The combined application of BMSC-Exos and TGF-β1 can more effectively promote the proliferation and migration of meniscus fibrocartilage cells, and holds promise as a new approach for the treatment of meniscus injuries.

The primary cilium is a protruding organelle present on many cell types with important roles for cell signaling. Defects in primary cilium formation and function are linked to numerous pathological conditions including neurodevelopmental defects, aging and cancer. The evaluation of ciliated cells within a cell sample traditionally relies on the visual assessment of cilia in fluorescence/confocal microscopy, after immunolabeling for ciliary markers highlighting the organelle for cilium counting. This can be influenced by operator-dependent factors, notwithstanding advanced image analysis tools developed to facilitate this labor-intensive evaluation. To address these limitations, a flow cytometry approach was trialed for neuroprogenitor cells (NPCs) differentiated from human iPSCs and stained for the ciliary markers ARL13B and PERICENTRIN measured on a flow cytometer, which detected positively-labeled ciliated cells. Specific staining was confirmed by microscopy and imaging flow cytometry, demonstrating for the first time the feasibility of cilium detection with axoneme and basal body markers colocalized on a single spot on human neuroprogenitor cell surface using a scalable, objective, and quantitative modality. Flow cytometry was able to measure changes in cilium frequency in a comparative analysis of neuroprogenitors derived from ciliopathy patients and healthy controls, underlining the discriminating capacity of this streamlined approach for the study of ciliary defects in a scalable and operator-independent manner.

[This corrects the article DOI: 10.1155/2019/6041816.].

In diabetic nephropathy (DN), classically activated macrophages (M1) are significantly increased, whereas alternatively activated macrophages (M2) are markedly decreased in the renal tissues. Mesenchymal stem cells (MSCs) have been shown to stimulate macrophages from M1 phenotype to M2 phenotype. Thus, we aimed to investigate whether the polarization of M1/M2 induced by MSCs was involved in DN. We injected human umbilical cord MSCs (UC-MSCs) into DN rats and found UC-MSC infusion reduced the infiltration of M1 macrophages and increased the infiltration of M2 macrophages in the glomerulus, thereby attenuating histopathological renal damage and improving renal inflammation and fibrosis in DN rats. Then, peritoneal macrophages were extracted and directed into M1 macrophages by lipopolysaccharides (LPS) in vitro. After coculturing UC-MSCs with M1 macrophages, we found that the M1 macrophage markers and related pro-inflammatory cytokines decreased. However, the expression of the M2 macrophage markers, as well as the anti-inflammatory cytokines, increased observably. Furthermore, UC-MSCs increased the expression of interleukin-4 receptor alpha chain (IL-4Rα) on macrophages by secreting interleukin-6 (IL-6); blocking IL-6 secretion inhibited the effect of UC-MSCs on M2 macrophage polarization. Then, we explored the mechanism by which M2 macrophages ameliorate DN in vitro and found that UC-MSC-induced M2 macrophages attenuated the secretion of the chemokine monocyte chemoattractant protein-1 (MCP-1) in hyperglycemia-induced mesangial cells, which led to reduced macrophage recruitment and infiltration. Moreover, UC-MSC-induced M2 macrophages inhibited transforming growth factor β (TGF-β) in glomerular mesangial cells. Our study proposes and discusses a mechanism by which MSCs promote the polarization of macrophages from M1 into M2 in the kidney, thereby ameliorating DN.

[This corrects the article DOI: 10.1155/2018/5420463.].

The present study aimed to evaluate the effect of apigenin (Api) on the osteogenic differentiation of adipose tissue-derived mesenchymal stem cells (ASCs) by stimulating autophagy. ASCs were isolated from fresh adipose tissues using mechanical and enzymatic digestion and characterized using flow cytometry. ASCs were treated with Api (0, 5, 10, 25, and 50 µM) for 48 and 72 h. After determining the optimal doses of Api (5 and 10 µM), ASCs were differentiated into the osteogenic lineage for 7 and 21 days. The expression of osteogenic and autophagy genes and proteins, as well as alkaline phosphatase (ALP) activity and calcium deposition, were assessed. About 94% of ASCs expressed CD73, CD90, and CD105, while 99% didn't express CD34 and CD45. Api treatment increased the expression of ALP, RUNX2, COL I, osteocalcin (OCN), ATG5, ATG7, and LC3A genes, and RUNX2, OCN, LC3-1, and LC3-II proteins dose-dependently. ALP activity and calcium deposition were significantly higher in Api-treated groups than in the control. Api increased the osteogenic differentiation of ASCs via inducing autophagy, an effect advantageous for enhancing SC differentiation efficiency.

The suboptimal reproductive performance of repeat-breeding (RB) cows is a major challenge for the dairy industry, leading to higher costs, prolonged calving intervals, and reduced productivity, negatively impacting herd productivity and economic viability. Among the associated factors, endometrial degeneration stands out, characterized by the replacement of functional tissue with fibrotic tissue, compromising uterine receptivity. In this context, regenerative therapy using mesenchymal stem cells (MSCs) has emerged as a promising alternative. This study evaluated the effects of intrauterine MSC inoculation in RB cows diagnosed with endometrial degeneration. Nine crossbred cows (Gyr × Holstein) were included and underwent clinical, cytological, microbiological, histopathological, ultrasonographic, and molecular evaluations on day 0 (pre-treatment) and day 30 (post-treatment). The results demonstrated endometrial remodeling, with fibrotic tissue replaced by loose connective tissue, increased vascularization, and the presence of new groups of endometrial glands. Doppler ultrasonography revealed enhanced blood flow of the endometrial mucosa and thickening of the uterine wall after therapy. qRT-PCR analysis indicated reduced expression of pro-inflammatory cytokines (IL-1β and IL-8), suggesting modulation of the uterine environment. Despite the observed tissue improvement and absence of adverse effects on ovarian function, none of the inseminated cows conceived. In conclusion, MSC therapy promoted favorable changes in the endometrium and uterine environment, although it did not result in pregnancy, highlighting the need for further studies to optimize dosage, administration route, and therapeutic response time.

Background: Growth Differentiation Factor 15 (GDF15), a stress-responsive cytokine, is involved in the progression of various cancers. However, its precise functional role and underlying mechanism in colorectal cancer (CRC) remain unclear.

Methods: GDF15 expression in CRC was analyzed using public databases and validated in patient tissues by Western blot. Functional assays, including colony formation, CCK-8, wound-healing, and Transwell, were performed on LOVO and HCT116 cells following GDF15 overexpression or knockdown to assess proliferation, migration, and invasion. Epithelial-mesenchymal transition (EMT) and stemness markers were examined by Western blot. Cancer stem cell properties were evaluated using a tumorsphere formation assay.

Results: GDF15 was significantly upregulated in CRC tissues at both mRNA and protein levels. In vitro, GDF15 overexpression in LOVO cells promoted proliferation, migration, and invasion and induced EMT, as evidenced by downregulated E-cadherin and upregulated vimentin and N-cadherin. Conversely, GDF15 knockdown in HCT116 cells produced opposite effects. Furthermore, GDF15 enhanced CRC cell stemness, increasing tumorsphere formation and upregulating stemness markers (CD133, SALL4, OCT4, NANOG). Clinically, high serum GDF15 levels were significantly associated with advanced age, late TNM stage, and elevated CEA, indicating its correlation with aggressive disease features.

Conclusion: Our findings demonstrate that GDF15 acts as a tumor promoter in CRC by driving EMT, facilitating proliferation and metastasis, and enhancing cancer stemness. This study identifies GDF15 as a potential biomarker and therapeutic target for CRC.