Search Results (4,135)

Coronary artery disease is a leading cause of morbidity and mortality in modern medicine. In contrast, surgical myocardial revascularization via coronary artery bypass grafting (CABG) remains the gold standard of treatment for complex multivessel disease. The great saphenous vein remains the most frequently used conduit due to its availability and technical simplicity, but its long-term patency is significantly inferior to that of arterial grafts. The primary pathological process responsible for vein graft failure is intimal hyperplasia, which represents a complex response of the vascular wall to surgical trauma, vein arterialization, inflammation, and hemodynamic stress. This process is characterized by endothelial dysfunction, inflammatory cell activation, proliferation and migration of vascular smooth muscle cells, and extracellular matrix remodeling. Underpinning these alterations are numerous molecular pathways, including NF-κB, MAPK, PI3K/Akt, TGF-β, and mTOR signaling, as well as substantial contributions from oxidative stress, cytokines, growth factors, and microRNAs. Contemporary research indicates that the phenotypic transformation of vascular smooth muscle cells constitutes the central event in the development of intimal hyperplasia. Understanding the cellular and molecular mechanisms underlying this disease’s onset enables the development of novel therapeutic strategies to preserve long-term graft patency. This review paper aims to provide a systematic overview of current knowledge regarding the molecular and cellular mechanisms of intimal hyperplasia development in vein grafts following CABG. Full article

Background: Cerebrovascular diseases have complex pathogenesis and pose a serious threat to human health; thus, novel diagnostic and therapeutic strategies are needed. Small extracellular vesicles (sEVs), commonly referred to as exosomes, are 30–150 nm lipid-bilayer vesicles that shield long noncoding RNAs (lncRNAs) from degradation. Because exosomal lncRNAs are more stable than free lncRNAs in blood and cerebrospinal fluid and can cross the blood–brain barrier, they are promising as biomarkers and therapeutic vectors. This review summarizes the roles and mechanisms of exosomal lncRNAs in cerebrovascular diseases. Methods: This narrative review is based on the experimental literature and focuses on the biological functions and regulatory mechanisms of exosomal lncRNAs in cerebrovascular disorders. Results: As competing endogenous RNAs (ceRNAs), they sequester microRNAs (miRNAs), thereby derepressing downstream target-gene expression and modulating neuronal injury (oxidative stress, apoptosis, neuroinflammation) through the nuclear factor kappa-B (NF-κB) and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathways. They show altered profiles in acute stroke (ischemic/hemorrhagic) correlated with neurological deficits, and are relevant to the early diagnosis of chronic diseases (atherosclerosis, aneurysm) and vascular dementia. Conclusions: Exosomal lncRNAs demonstrate promising translational potential in preclinical studies because they combine exosome delivery capabilities with lncRNA regulatory functions, although clinical validation remains limited. Full article

Cancer remains a highly complex and heterogeneous disease, causing major morbidity and mortality worldwide despite advances in diagnosis and treatment. The hallmarks of cancer enlighten the biological mechanisms supporting tumourigenesis and malignant evolution, while helping to identify potential therapeutic targets. Medical cannabis has mostly been used in oncology for supportive care, but increasing preclinical evidence suggests interference with cancer-related signalling pathways. This narrative review summarizes the current evidence on cannabinoids, in particular the phytocannabinoids cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), framing their prospective anticancer effects in the hallmarks of cancer. Preclinical studies imply that CBD exerts antiproliferative effects by modulating oncogenic signalling pathways, including EGFR, PI3K/AKT, RAS/RAF/ERK, mTOR and Wnt/β-catenin, while also influencing tumour suppressor pathways involving p53, p21 and p27, causing cell cycle arrest. CBD has additionally been shown to promote programmed cell death via mitochondrial dysfunction and autophagy, altering cancer metabolism as well. Furthermore, CBD has shown anti-invasive and antiangiogenic properties and also appears to modulate immune responses and interactions with the tumour microenvironment, including emerging links with the microbiome. Overall, cannabinoids exhibit biologically plausible antitumour activity across multiple cancer hallmarks and may present promising candidates for combination therapeutic strategies. Nonetheless, the current evidence remains predominantly preclinical, and robust translational studies and clinical trials are needed to clarify their pharmacokinetic and pharmacodynamic profiles, determine their clinical efficacy and safety while assessing their potential integration into multimodal cancer treatment. Full article

Hair follicle stem cells (HFSCs) are critical for hair follicle (HF) morphogenesis and cyclic hair regeneration. Periostin (POSTN), an extracellular matrix protein involved in tissue development and skin cell regulation, remains poorly characterized in HFSCs. In this study, we constructed CRISPR/Cas9 vectors targeting POSTN and validated their editing efficiency in primary HFSCs. POSTN editing significantly suppressed cell proliferation and promoted apoptosis. Transcriptomic analysis identified 988 differentially expressed genes (DEGs) enriched in immune responses and MAPK, PI3K–Akt, and cAMP pathways. Metabolomic analysis revealed 98 differential metabolites (DMs) associated with nucleotide metabolism and FoxO, AMPK, and cAMP pathways. Integrated multi-omics analysis showed extensive correlations between DEGs and DMs, and highlighted the cAMP pathway as the core regulatory axis. Western blot (WB) validation confirmed that POSTN editing reduced PKA and CREB phosphorylation, indicating inhibition of the cAMP/PKA/CREB signaling. These findings demonstrate that POSTN regulates HFSCs’ proliferation and apoptosis partially via the cAMP/PKA/CREB pathway, providing novel insights into the functional regulation of HFSCs. Full article

Background: High-altitude hypobaric hypoxia (HH) is a major environmental stressor that impairs cognitive function, yet effective and widely available therapeutics remain limited. Although Rhodiola rosea has shown neuroprotective effects, its resource scarcity restricts large-scale application. Cistanche tubulosa (Schrenk) Wight, a traditional Chinese functional food, has been increasingly used in health supplements due to its anti-fatigue, anti-dementia, and memory-enhancing properties, suggesting potential benefits against hypoxia-induced cognitive impairment. Objective: This study aimed to investigate the effects of C. tubulosa ethanol extract (CTE) on hippocampal tissue and gut microbiota upon chronic HH exposure using SPF male Sprague–Dawley (SD) rats. Methods: A total of 60 male SD rats were randomly assigned to six experimental groups (n = 10 per group): normoxic control, untreated HH model, positive control (R. rosea), and low-, medium-, high-dose CTE treatment groups. Behavioral tests (Morris water maze), hippocampal histopathology, serum and hippocampal oxidative stress markers (SOD, GSH-Px, MDA), expression of PI3K/Akt/mTOR-HIF-1α signaling pathway proteins (by immunohistochemistry), and gut microbiota composition (by 16S rRNA sequencing) were evaluated. Results: The results demonstrated that CTE significantly improved cognitive function, enhanced SOD and GSH activities, and reduced MDA levels in both hippocampus and serum. CTE also modulated the expression of PI3K/Akt/mTOR-HIF-1α pathway proteins in the hippocampus. Furthermore, CTE altered gut microbial diversity and abundance, increasing the proportion of beneficial bacteria, which may further influence hippocampal function via the gut–brain axis. Conclusion: These findings provide scientific evidence for the application of C. tubulosa as a potential health supplement for high-altitude adaptation and lay a foundation for subsequent research. Full article

Enhydrin, a melampolide-type sesquiterpene lactone abundant in the leaves of yacon (Smallanthus sonchifolius), has not previously been investigated for its anti-prostate cancer activity. This study investigated the antiproliferative effects of enhydrin in human prostate cancer cells, its regulatory effects on apoptosis-related molecules, and its impact on the PI3K/AKT and NF-κB signaling pathways. Three prostate cancer cell lines (PC3, DU145, and LNCaP) were treated with enhydrin, and its effects were analyzed using cell viability assays, morphological observation, flow cytometry, apoptosis-focused TaqMan qPCR array, qRT-PCR, and Western blotting. In vivo antitumor activity was assessed in a PC3 xenograft mouse model. Enhydrin reduced cell viability in a dose- and time-dependent manner, induced morphological changes associated with cytotoxicity, and caused G1 cell-cycle arrest. Gene expression analysis revealed downregulation of PI3K/AKT- and NF-κB-related genes and modulation of BCL2 family genes toward a pro-apoptotic profile, which was confirmed at both mRNA and protein levels. In vivo, enhydrin suppressed tumor growth without significant body-weight loss. These findings suggest that enhydrin exerts antitumor effects in prostate cancer by reducing the expression of PI3K/AKT and NF-κB related molecules and modulating apoptosis-related proteins. Although additional studies are required to determine pathway activity, directly confirm apoptosis, and evaluate normal-cell cytotoxicity and the therapeutic window, these findings provide preliminary biological evidence of the effects of enhydrin in prostate cancer models. Full article

Background/Objectives: Achondroplasia is the most common genetic skeletal dysplasia associated with disproportionate short stature and is primarily caused by gain-of-function variants in the fibroblast growth factor receptor 3 (FGFR3) gene. Constitutive FGFR3 activation disrupts growth plate homeostasis and endochondral ossification through complex alterations in chondrocyte proliferation, differentiation, hypertrophy, extracellular matrix organization, and intracellular signaling. The increasing understanding of these mechanisms has enabled the transition from exclusively supportive management toward disease-modifying and precision-based therapeutic strategies. This narrative review aimed to critically synthesize current evidence on the genetic basis, molecular pathogenesis, growth plate abnormalities, and current and emerging targeted therapies in achondroplasia. Methods: A narrative literature review was conducted using PubMed/MEDLINE, Scopus, and Web of Science Core Collection, with Google Scholar used as a supplementary source, together with manual screening of the reference lists of relevant original studies, clinical trials, reviews, consensus documents, and clinical guidelines. The principal literature search covered publications from January 2010 to March 2026, while selected seminal primary studies published before 2010 were included when necessary to document the original identification of pathogenic FGFR3 variants and foundational mechanisms of FGFR3-mediated growth plate regulation. Particular emphasis was placed on FGFR3 variants, receptor activation mechanisms, growth plate dysfunction, intracellular signaling pathways, vosoritide, C-type natriuretic peptide-based therapies, FGFR3 inhibitors, ligand–receptor blockade, drug repurposing, Wnt/β-catenin modulation, and gene-based therapeutic approaches. Results: Achondroplasia is characterized by marked molecular homogeneity, with the recurrent p.Gly380Arg substitution accounting for most cases. Mutant FGFR3 displays sustained activity through partial ligand independence, enhanced receptor dimerization and kinase activation, increased receptor stability, and reduced degradation. Excessive signaling through MAPK/ERK, STAT, PI3K/AKT, IHH/PTHrP, and related pathways impairs chondrocyte proliferation and hypertrophic differentiation, alters extracellular matrix turnover, disrupts primary cilium function, and reduces longitudinal bone growth. Vosoritide provides clinical proof that pharmacological modulation of FGFR3-related signaling can improve growth velocity. Additional therapeutic strategies under clinical or preclinical investigation include long-acting CNP analogues, selective FGFR inhibitors, decoy receptors, RNA aptamers, repurposed drugs, Wnt/DKK1 pathway modulation, and gene- or enhancer-targeted interventions. Conclusions: Achondroplasia is increasingly understood as a disorder of dysregulated growth plate signaling rather than solely a condition of reduced stature. Although vosoritide has established the feasibility of disease-modifying treatment, substantial uncertainty remains regarding final adult height, skeletal proportionality, cranio-spinal development, orthopedic outcomes, and long-term safety. Future progress will depend on mechanistically informed therapeutic combinations, improved biomarkers, advanced cellular and animal models, and long-term clinical and real-world evidence. Full article

The ruminal epithelium plays a central role in nutrient absorption, epithelial barrier function, and mucosal immune defense. However, the molecular mechanisms by which dietary Perilla frutescens seeds (PFS) regulate ruminal epithelial immunity remain poorly understood. This study investigated the transcriptomic responses of the sheep ruminal papilla to dietary PFS supplementation. Forty-five male Tan sheep were assigned to three dietary treatments (n = 15 per group): a low-concentrate diet (LC), a high-concentrate diet (HC), and the LC diet supplemented with 3% PFS (LC + PFS). After an 84-day feeding trial, ruminal papilla tissues from six animals per group were randomly subjected to RNA sequencing and integrated bioinformatic analyses, covering all three pairwise comparisons (LC vs. HC, HC vs. LC + PFS, and LC vs. LC + PFS). The LC vs. LC + PFS comparison served as the direct assessment of PFS effects under the same basal diet, whereas HC vs. LC + PFS was treated as a cross-dietary comparison. LC vs. HC yielded 387 differentially expressed genes (DEGs), HC vs. LC + PFS yielded 104 DEGs, and LC vs. LC + PFS yielded 33 DEGs, with predominant enrichment in metabolic and stress-adaptive pathways (AMPK, MAPK, PI3K-Akt). The latter were mainly associated with metabolic and structural pathways. Propionate and valerate were negatively correlated with several interferon-signaling and antigen-presentation genes. Collectively, the direct LC vs. LC + PFS comparison demonstrates that PFS supplementation under physiological conditions is associated with targeted metabolic modulation. Meanwhile, the cross-dietary HC vs. LC + PFS comparison reveals that, relative to high-concentrate feeding, the PFS-supplemented low-concentrate feeding regimen is transcriptionally associated with enhanced immune surveillance capacity in a non-inflammatory manner. These findings provide transcriptomic evidence supporting the potential of PFS as a modulator of ruminal epithelial homeostasis and offer a foundation for further investigation into its application as a functional feed ingredient. Full article

Background/Objectives: Exposure to lead (Pb) is a serious public health concern for which there is no safe level. The aim of this study was to investigate the toxicity of Pb to undifferentiated (uSH-SY5Y) and differentiated (dSH-SY5Y) human neuroblastoma cells and to evaluate gene transcription in response to sub-lethal lead exposure. Methods: Pb was applied to uSH-SY5Y and dSH-SY5Y cells across a concentration range of 0–5 mM for 4, 6, and 24 h, and cell viability was assessed using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase assays. Results: Pb induced a significant concentration- and exposure-dependent reduction in cell viability. Pb significantly impacted cellular bioenergetics and reduced ATP production in a concentration- and exposure duration-dependent manner, triggering elevated levels of deleterious reactive oxygen species. Transcriptomic profiling in dSH-SY5Y cells after a sub-lethal 24 h exposure to 1.25 mM Pb revealed 757 upregulated and 2206 downregulated genes. From Gene Ontology and KEGG pathway enrichment analysis, biological processes were predominantly associated with immune and inflammatory processes, including cytokine-mediated signalling. Upregulated differentially expressed genes (DEGs) included those for PI3K/Akt and cytokine signalling, and downregulated DEGs included genes linked to spinocerebellar ataxia, mitophagy, cytokine receptor interaction and cellular metabolism. Protein–protein interaction analysis identified six key hub-upregulated genes with a primarily inflammatory focus (CD44, CXCR4, PTGS2, IL1β, TNF, MMP9) and one downregulated gene (CD4) as potential regulators of Pb-induced cellular responses. Disease association analyses revealed links to chemical carcinogenesis and neurodegenerative diseases. Conclusions: Collectively, these findings provide molecular insights into Pb-induced neurotoxicity and highlight a network of genes that converge on neurological and inflammatory pathways, which are candidates for further mechanistic investigation and possible therapeutic targeting following Pb poisoning. Full article

Mesenchymal stem/stromal cells (MSCs) are promising candidates in regenerative medicine, but their effectiveness is significantly influenced by the surrounding metabolic and nutritional conditions. Increasing evidence suggests that lipids act not only as energy sources but also as regulators of MSC fate. This review explores how lipid metabolism influences the balance among stemness, immunomodulation, and differentiation into adipogenic or osteogenic lineages. It does so through mechanisms such as fatty acid uptake, β-oxidation, de novo lipogenesis, and membrane remodeling, all orchestrated by CD36, carnitine palmitoyltransferase 1A, PPARγ, AMP-activated protein kinase, and the PI3K/AKT/mTOR pathway. We then examine how diet reshapes the MSC lipidome: obesity and high-fat diets promote adipogenesis and senescence, while omega-3 fatty acids, caloric restriction, micronutrients, and a balanced microbiota help preserve regenerative capacity. Lastly, we discuss how combining lipidomics with multi-omics could uncover lipid-metabolic signatures and regulatory nodes that connect diet to MSC function. Overall, the diet–lipid–MSC axis emerges as a modifiable determinant of MSC function. Full article

Centella asiatica (L.) Urb. (Apiaceae) is widely incorporated into dermatological and wound-healing formulations, where dechlorophylization is commonly used to improve extract stability, although its biological consequences are not fully understood. In this study, an ethanolic extract of C. asiatica leaves (CAE) was compared with a dechlorophylized C. asiatica extract (DCAE) in terms of cytotoxicity, wound-healing, anti-inflammatory, and antimicrobial activities, complemented by network pharmacology analysis. DCAE exhibited improved cytocompatibility, remaining non-cytotoxic up to 100 µg/mL, whereas CAE showed cytotoxic effects above 25 µg/mL. In contrast, CAE demonstrated superior wound-healing performance, reducing the residual wound area to 21.77% compared with 36.81% for DCAE and inducing higher Ki67 expression (1.94-fold versus 1.58-fold). These findings suggest that chlorophyll-associated constituents may contribute to keratinocyte proliferation and re-epithelialization. Although DCAE was enriched in pentacyclic triterpenes, including asiatic acid, asiaticoside, madecassic acid, and madecassoside, it showed stronger anti-inflammatory effects by more effectively suppressing CXCL10, IL-6, TNF-α, and IL-8 expression. Both extracts displayed weak antibacterial activity but moderate antifungal effects against Candida albicans, likely mediated through membrane disruption. Network pharmacology further indicated that wound-healing activity is associated with the regulation of COL1A1 and VEGFA through quercetin, kaempferol, and asiatic acid by way of the PI3K-Akt and MAPK signaling pathways, whereas anti-inflammatory effects involve modulation of PTGS2 and TNF through the NF-κB and IL-17 pathways. Overall, DCAE enhances cytocompatibility and anti-inflammatory activity, while CAE retains stronger regenerative capacity. These findings support the rational design of tailored formulations for specific dermatological applications, such as promoting wound repair or alleviating chronic skin inflammation. Full article

Kaempferol, a naturally occurring dietary flavonoid abundantly found in various fruits and vegetables, has garnered significant attention due to its diverse pharmacological properties, most notably its potent anticancer activity. In the orchestration of cancer pathogenesis, the PTEN/PI3K/AKT/mTOR signaling cascade plays a pivotal role, where aberrant activation or dysregulation of this pathway drastically accelerates tumor cell proliferation, survival, and metabolic reprogramming, thereby driving tumorigenesis. Moreover, non-coding microRNAs (miRNAs) have emerged as key modulators involved in regulating this pathway, functioning as either oncogenes or tumor suppressors to determine cancer cell fate. Previous studies have demonstrated that kaempferol and its derivatives, owing to their molecular structures, suppress the PI3K/AKT/mTOR signaling pathway either directly or indirectly, thereby playing a critical role in inhibiting cancer cell proliferation. Hence, this comprehensive review elucidates the therapeutic potential of kaempferol and its derivatives, focusing specifically on their molecular mechanisms in modulating the PTEN/PI3K/AKT/mTOR pathway. Furthermore, this review highlights the crosstalk between kaempferol and the specific miRNAs targeting these signaling components in various cancer types. Full article

Background/Objectives: While currently termed premature ovarian insufficiency (POI), premature ovarian failure (POF) remains a prominent driver of female infertility with a molecular pathogenesis that is still lacking comprehensive clarification. In in vitro studies, the pathology of POI is commonly simulated through a well-characterized model involving VCD (4-vinylcyclohexene diepoxide)-mediated cytotoxicity within KGN-derived human granulosa cells. However, the key regulatory molecular networks involved in this process are still poorly characterized. Although microRNAs (miRNAs) have emerged as critical regulators in ovarian function decline, the specific role and underlying mechanism of miR-27b-3p in POI remain elusive. Methods: A VCD-induced KGN cell injury model was established by treating cells with 1.0 mM VCD for 24 h. Cell viability, apoptosis rate, and miR-27b-3p expression were assessed by CCK-8 assay, flow cytometry, and RT-qPCR, respectively. Overexpression and targeted suppression of miR-27b-3p were achieved by introducing its specific mimics and inhibitors, respectively. Target identification was conducted via bioinformatic prediction, EdU incorporation, Western blot, and dual-luciferase reporter assays. Functional rescue experiments were carried out by co-transfection with a PAPPA-overexpressing plasmid (oe-PAPPA). IGF-1 secretion was quantified by ELISA, and phosphorylation of IGF1R and AKT was analyzed by Western blot to determine whether miR-27b-3p modulates cellular phenotypes via the PAPPA–IGF-1–PI3K/AKT axis. Exogenous IGF-1 supplementation was further applied to confirm pathway dependence. Results: VCD treatment dose-dependently restrained cellular growth and stimulated apoptotic pathways in KGN cells; paralleling these phenotypic changes, miR-27b-3p abundance was remarkably increased. Ectopic expression of miR-27b-3p exacerbated VCD-induced growth inhibition and apoptosis, whereas its inhibition conferred cytoprotective effects. Through the integration of computational predictions and dual-luciferase reporter systems, PAPPA was definitively established as a direct downstream target of miR-27b-3p. miR-27b-3p negatively regulated both PAPPA mRNA and protein levels, thereby impairing PAPPA-mediated cleavage of IGF-binding proteins (e.g., IGFBP4) and subsequent release of free IGF-1. This led to reduced IGF-1 secretion and significantly diminished phosphorylation of IGF1R and AKT. Remarkably, PAPPA overexpression effectively reversed the detrimental effects of miR-27b-3p, and exogenous IGF-1 supplementation similarly attenuated miR-27b-3p–mediated proliferation arrest and pro-apoptotic phenotypes. Conclusions: This study uncovers a novel pathogenic mechanism whereby miR-27b-3p exacerbates VCD-induced granulosa cell injury by directly targeting PAPPA, suppressing IGF-1 release, and consequently inhibiting the PI3K/AKT pro-survival signaling pathway. A novel perspective on the fundamental basis of POI is established by this research, which further posits therapeutic manipulation of the miR-27b-3p/PAPPA/IGF-1 module as a prospective treatment for disrupted ovarian function. Full article

To investigate the role and underlying mechanisms of TIMM8A in breast cancer progression. The expression of TIMM8A in breast cancer tissues and cell lines was assessed. Functional assays were performed to evaluate the effects of TIMM8A knockdown on proliferation, metastasis, and apoptosis in BT549 and MCF-7 cells. Co-immunoprecipitation (Co-IP) and ubiquitination assays were used to examine the interaction between TIMM8A and HSPA9, as well as the involvement of the E3 ubiquitin ligase RNF4. PI3K/AKT pathway activity was assessed by Western blotting. In vivo tumor growth was evaluated using a xenograft mouse model. TIMM8A was significantly upregulated in breast cancer tissues and cell lines, and high TIMM8A expression correlated with poor prognosis. TIMM8A knockdown suppressed proliferation and metastasis while inducing apoptosis in vitro. Mechanistically, TIMM8A interacted with HSPA9 and maintained its protein stability by inhibiting RNF4-mediated ubiquitination and degradation, thereby sustaining PI3K/AKT signaling activation. Conversely, TIMM8A depletion reduced HSPA9 stability and attenuated the pathway. Rescue experiments confirmed that HSPA9 overexpression restored PI3K/AKT activation and reversed TIMM8A-knockdown-induced malignant suppression. In vivo, TIMM8A silencing efficiently inhibited tumor growth, accompanied by reduced HSPA9 and Ki-67 expression and decreased PI3K/AKT phosphorylation. TIMM8A promotes breast cancer progression through the TIMM8A/HSPA9/PI3K/AKT regulatory axis, highlighting TIMM8A as a promising prognostic biomarker and potential therapeutic target for breast cancer. Full article

Tendinopathies represent a major clinical challenge. Vasculature, neuromuscular junctions, low cellularity, and slow extracellular matrix (ECM) turnover restrict endogenous repair and predispose injured tendons to fibrosis, mechanical weakness, and reinjury. Current therapeutic strategies including rehabilitation protocols, anti-inflammatory medications, platelet-rich plasma (PRP) injections, and surgical repair primarily address symptoms or structural deficits without correcting the underlying biological limitations of tendon healing. Cell-based therapies have emerged as a promising regenerative approach aimed at restoring tissue homeostasis through modulation of angiogenesis, collagen synthesis, immune responses, and tenogenic differentiation. Mesenchymal stem cells (MSCs), adipose-derived stem cells (ADSCs), tendon-derived stem cells (TDSCs), induced pluripotent stem cells (iPSCs), differentiated tenocytes, and extracellular vesicle (EV)-based products have demonstrated the ability to enhance vascularization, promote type I collagen remodeling, suppress excessive inflammation, and stimulate tenocyte lineage commitment. These effects are mediated through paracrine signaling, growth factor secretion, and activation of key pathways, including HIF-1α, TGF-β/SMAD, NF-κB, and PI3K/Akt signaling. Despite promising preclinical data, significant translational challenges remain, including limited cell survival at the injury site, variability in cell sources and dosing, immunogenicity, risk of misdifferentiation, and lack of standardization across clinical protocols. Emerging strategies such as genetic modification, hypoxic preconditioning, scaffold-based delivery systems, and extracellular vesicle engineering aim to enhance therapeutic efficacy and reproducibility. This review synthesizes current evidence on cell-based tendon repair, critically evaluates mechanistic insights, clinical trials, and translational barriers, and outlines future directions toward biologically informed regenerative therapies. Full article