Advancements and Challenges in Stem Cell Transplantation for Regenerative Medicine

Heliyon, Journal Year: 2024, Volume and Issue: 10(16), P. e35836 - e35836

Published: Aug. 1, 2024

Stem cell transplantation has emerged as a promising avenue in regenerative medicine, potentially facilitating tissue repair degenerative diseases and injuries. This review comprehensively examines recent developments challenges stem transplantation. It explores the identification isolation of various types, including embryonic, induced pluripotent, adult cells derived from multiple sources. Additionally, highlights tissue-specific applications these cells, focusing on bone cartilage regeneration, treatment neurological disorders, management hematological conditions. Future advancements effective resolution current will be crucial fully realizing potential medicine. With responsible ethical practices, field can transform disease injury treatment, ultimately improving quality life for countless individuals.

Language: Английский

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Inhibition of Rho GEFs attenuates pulmonary fibrosis through suppressing myofibroblast activation and reprogramming profibrotic macrophages

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 11, 2025

Idiopathic pulmonary fibrosis has a poor prognosis, with existing medications only partially alleviating symptoms, highlighting the urgent need for new therapeutic approaches. The dysregulations of Rho GTPases/ROCK are related various diseases, including fibrosis. Nevertheless, development drugs treatment predominantly concentrated on ROCK inhibitors. Small GTPases have been historically recognized as "undruggable". Here, we explore novel GEFs inhibitor GL-V9, and find that GL-V9 alleviates bleomycin-induced in mice by inhibiting myofibroblast activation reprogramming profibrotic macrophages. Distinct from mechanisms first-line drug Nintedanib, binds to DH/PH domain block GTPase signaling. This action subsequently suppresses interfering GTPase-dependent cytoskeletal reorganization activity MRTF YAP, inhibits M2 macrophage polarization modulating RhoA/STAT3 activity. discovery regulatory suggests targeting represents potent strategy treatment.

Language: Английский

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Elucidating the causal associations and mechanisms between circulating immune cells and idiopathic pulmonary fibrosis: new insights from Mendelian randomization and transcriptomics

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 17, 2025

Growing evidence indicates an association between circulating immune cell phenotypes and idiopathic pulmonary fibrosis (IPF). Although studies have attempted to elucidate the causal relationship two, further clarification of specific mechanisms linkages is warranted. We aimed conduct a two-sample Mendelian randomization (MR) analysis with transcriptomics data cells IPF explore potential biomarkers. first explored bidirectional using MR analysis. Genome-wide for phenotype were obtained from publicly available databases. A standardized instrumental variable screening process was used select single nucleotide polymorphisms (SNPs) inclusion in MR. Five methods represented by IVW assess effects. Subsequently, SNP-nearest genes combined subjected multiple bioinformatics analyses such as TIMER, WGCNA, functional enrichment analysis, protein-protein interaction ROC identify Finally, single-cell RNA sequencing (scRNA-seq) validate our findings The study identified 27 causally associated IPF, which 20 decreased risk developing 7 increased risk. CTSB (AUC=0.98), IL10 (AUC=0.83), AGER (AUC=0.87) promising biomarkers IPF. Single showed differences CD14+ CD16+ monocytes, monocytes Granulocyte-monocyte progenito group healthy control group. three hub highly expressed subsets patients. It underscores feasibility Our demonstrates associations through genetic identifies CTSB, IL10, These provide guidance future clinical basic research.

Language: Английский

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Myeloid‐Mesenchymal Crosstalk in Lung Fibrosis

Comprehensive physiology, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 1, 2025

ABSTRACT Idiopathic pulmonary fibrosis (IPF) is a chronic respiratory disease characterized by progressive scarring of the lung parenchyma. While two drugs have been approved US Food and Drug Administration (FDA) for IPF, median survival remains limited at 3 years, discovery novel therapeutic targets urgently needed. Recent studies indicate that immune cells play critical role in regulating fibrosis. In this Mini Review, we discuss recent literature focused on myeloid lineage serve as key agents pathologic interorgan communication These are recruited from bone marrow found to be drivers fibrotic process lung.

Language: Английский

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Identification of glycolysis-related gene signatures for prognosis and therapeutic targeting in idiopathic pulmonary fibrosis

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 28, 2025

Background Glycolysis plays a crucial role in fibrosis, but the specific genes involved glycolysis idiopathic pulmonary fibrosis (IPF) are not well understood. Methods Three IPF gene expression datasets were obtained from Gene Expression Omnibus (GEO), while glycolysis-related retrieved Molecular Signatures Database (MsigDB). Differentially expressed (DEGRGs) identified using “limma” R package. Diagnostic (GRGs) selected through least absolute shrinkage and selection operator (LASSO) regression support vector machine-recursive feature elimination (SVM-RFE). A prognostic signature was developed LASSO regression, time-dependent receiver operating characteristic (ROC) curves generated to evaluate predictive performance. Single-cell RNA sequencing (scRNA-seq) data analyzed examine GRG across various cell types. Immune infiltration analysis, Set Enrichment Analysis (GSEA), Variation (GSVA) performed elucidate potential molecular mechanisms. bleomycin (BLM)-induced mouse model used for experimental validation via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results 14 GRGs ( VCAN, MERTK, FBP2, TPBG, SDC1, AURKA, ARTN, PGP, PLOD2, PKLR, PFKM, DEPDC1, AGRN, CXCR4 ) as diagnostic markers IPF, with seven SDC1 forming demonstrating power (AUC: 0.831–0.793). scRNA-seq revealed cell-type-specific expression, particularly macrophages fibroblasts. analysis linked imbalanced immune responses. Experimental bleomycin-induced confirmed upregulation of (such CXCR4). Drug prediction inhibitors Tozasertib Plerixafor CXCR4) therapeutic agents. Conclusion This study identifies biomarkers highlights their modulating responses within fibrotic lung microenvironment. Notably, MERTK , associated pathways progression represent targets. Our findings provide insights into metabolic reprogramming suggest that targeting may offer novel pharmacological strategies antifibrotic therapy.

Language: Английский

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Assessment of Imatinib Anti-Remodeling Activity on a Human Precision Cut Lung Slices Model

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8186 - 8186

Published: July 26, 2024

Recent studies have emphasized the critical role of alteration in cellular plasticity development fibrotic disorders, particularly pulmonary fibrosis, prompting further investigation into molecular mechanisms and therapeutic approaches. In this context, Precision Cut Lung Slices (PCLSs) emerge as a valuable ex vivo research tool. The process PCLSs generation preserves most features naïve lung tissue, such its architecture complex composition. We previously stimulated normal with two different stimuli (fibrotic cocktail, composed by platelet lysate TGFβ, or neutrophil extracellular traps) we observed significant elevation Epithelial-Mesenchymal Transition (EMT) markers from 24 h to 72 culture. aim our work was exploit based model EMT, evaluate effect imatinib, an old tyrosine kinase inhibitor reported anti-remodeling activities vitro animal models. Imatinib treatment significantly decreased α-SMA collagen expression already starting on PCLS. showed toxicity unstimulated cells (3-fold increase

Language: Английский

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The possible role of hypoxia-induced exosomes on the fibroblast metabolism in idiopathic pulmonary fibrosis

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 181, P. 117680 - 117680

Published: Nov. 16, 2024

Language: Английский

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Quantitative proteomic landscape of the pathophysiology of adhesive arachnoiditis and its clinical significance: Structure and mechanism of TNC and RANBP1 proteins

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: unknown, P. 138444 - 138444

Published: Dec. 1, 2024

Language: Английский

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