Search Results (2,044)

Background/Objectives: Neurodegenerative diseases (NDs) have a severe impact on patients’ quality of life, and effective treatments remain limited. As the focus is on treating the symptoms, the root cause of the problem is commonly not addressed. Mesenchymal stem cells show an emerging potential due to the ability for self-renewal combined with their capability for differentiation into various cell lines, which makes them a strong candidate for regenerative therapies in general, and for application in neurological issues in particular. This article provides an overview of the safety, efficacy, and challenges associated with the use of mesenchymal stem cells (MSCs) and their derived secretome in clinical and preclinical models of Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS). Methods: A systematic search was conducted on PubMed to identify published studies providing clinical and preclinical evidence on the use of MSCs in neurodegenerative disorders. Results: Overall, the literature consistently indicates that MSCs and their derivatives exert disease-modifying effects across multiple NDs. Across AD, PD, HD and ALS, preclinical studies uniformly report improvements in behavioural outcomes, attenuation of neuroinflammation, and neuroprotective effects, largely mediated by MSCs’ paracrine signalling rather than direct cell replacement. Clinical studies to date consistently support the safety and feasibility of MSC-based therapies, while efficacy signals remain modest, heterogeneous and predominantly short-term, highlighting the need for larger, well-controlled trials. Conclusions: Integration of genetic engineering, preconditioning, and EV technology may represent an emerging therapeutic approach that may complement existing neuroregeneration treatments, offering a scalable and minimally invasive frontier to improve long-term clinical outcomes in patients with AD, PD, HD, and ALS. Full article

Mesenchymal stem cells (MSCs) have been widely investigated in regenerative medicine owing to their immunomodulatory activity, paracrine signaling, and multilineage differentiation potential. However, accumulating clinical and preclinical evidence indicates that conventional MSC therapies based on single-cell injection often produce transient benefits due to rapid post-transplant cell loss and poor engraftment. These observations suggest that the limited efficacy of MSC therapy is not determined solely by cell type or disease context but may also be influenced by the delivery strategy. In this review, we focus on MSC-based cell sheet studies as an approach to improve cell retention and therapeutic persistence. Building on the clinical validation of cell sheet technology, we critically summarize preclinical evidence across distinct tissue environments. Preclinical studies in cardiac and cutaneous repair models demonstrate that MSC sheets enhance cell retention, sustain paracrine signaling, and promote tissue-level regeneration. Together, these findings highlight that effective MSC sheet therapy requires organ-specific, cell-source-dependent design strategies rather than a uniform approach across tissues. Finally, we propose that the MSC sheet engineering represents not a technical adjustment, but a conceptual shift from transient cell delivery toward structurally integrated, tissue-level regeneration engineering. Full article

Background: Extracellular vesicles (EVs) have emerged as promising cell-free therapeutic agents in regenerative medicine due to their ability to deliver bioactive molecules with enhanced stability and low immunogenicity. Their potential to replicate stem cell functions without the risks of live-cell transplantation has catalyzed a surge in global research. Objective: This study aims to perform a scientometric analysis of EV-based regenerative medicine research from 2014 to 2024, identifying publication trends, influential contributors, thematic clusters, and translational challenges. Methods: Data were retrieved from the Web of Science Core Collection and analyzed using CiteSpace software. The analysis included journal impact mapping, co-authorship networks, co-citation analysis, and thematic cluster identification. Metrics such as citation bursts, total link strength, and silhouette values were used to assess influence and thematic coherence. Results: The most prolific journals were Stem Cell Research & Therapy and International Journal of Molecular Sciences. China led in publication volume, while the USA dominated citation impact. Foundational works by Théry and Lai, including the MISEV guidelines, shaped methodological standards. Nine thematic clusters were identified, including oxidative stress, small EVs, mesenchymal stromal cells, muscle regeneration, and chronic kidney disease. A strategic shift toward engineered EVs and novel sources such as iPSCs and macrophages was evident. Key translational barriers include lack of standardization, scalability issues, and regulatory ambiguity. Conclusions: EV-based therapies are transitioning from foundational research to clinical application. Overcoming methodological and regulatory challenges will be critical to realizing their full therapeutic potential in regenerative medicine. Full article

Autogenous grafts remain the gold standard for repairing extensive maxillofacial bone defects, but their associated morbidity motivates the search for alternative strategies in tissue bioengineering. Deciduous dental pulp stem cells (DDPSCs) represent a promising cell source due to their accessibility, multipotency, and osteogenic potential, while nanostructured carbonated hydroxyapatite (cHA) microspheres exhibit biochemical similarity to bone mineral and favorable bioabsorption. This study investigated the osteogenic response induced by the association of DDPSCs with cHA in a rat calvaria critical-size defect model. DDPSCs were expanded, seeded onto cHA microspheres, and characterized in vitro prior to bilateral implantation in 12 Wistar rats, with each animal receiving cHA + DDPSC on the right defect and acellular cHA on the left. After 60 and 90 days, histological and histomorphometric analyses revealed new bone formation in both groups, predominantly from the defect margins toward the center. At 60 days, no significant difference in newly formed bone was observed between groups (p = 0.249). At 90 days, the DDPSC + cHA group demonstrated significantly greater bone formation compared with acellular cHA (median 40.70 vs. 11.10 histomorphometric points; p = 0.028) and significant reduction in connective tissue (p = 0.028). Complete scaffold resorption was observed in all DDPSC-treated defects at 90 days, whereas residual biomaterial persisted in the cHA group (p = 0.015), indicating progressive cHA resorption over time. These findings suggest that combining DDPSCs with cHA enhances bone regeneration and that this synthetic, bioabsorbable scaffold represents a promising strategy for future applications in bone tissue engineering. Full article

Acute and chronic kidney diseases remain significant challenges in regenerative medicine, with few therapies capable of reversing tissue injury or preventing progression. Bone marrow mesenchymal stem cell-derived exosomes (BM-MSC-Exos) are nanosized vesicles (30–150 nm) that have emerged as multifunctional nanotheranostic platforms, combining targeted therapeutic activity with imaging-enabled monitoring. In renal pathophysiology, BM-MSC-Exos exert anti-inflammatory, anti-fibrotic, angiogenic, and pro-regenerative effects. These actions are mediated by microRNAs, messenger RNAs, mitochondrial regulators, and bioactive proteins that modulate epithelial repair and immune responses. Recent bioengineering advances enable more precise BM-MSC-Exos design, including enrichment with synthetic RNAs or gene-editing components and membrane functionalization to enhance kidney tropism. In parallel, fluorescence, bioluminescence, and nanoparticle-based approaches support in vivo tracking. These tools allow real-time assessment of biodistribution and tubular uptake, strengthening evidence for target engagement. This review synthesizes current knowledge on BM-MSC-Exos in renal repair. We summarize contemporary strategies for cargo and surface engineering, outline imaging methodologies for in vivo tracking, and discuss how administration routes influence renal targeting. We also provide an updated overview of clinical trials evaluating exosomes as therapeutic agents or biomarkers in nephrology. Collectively, engineered BM-MSC-Exos represent a promising and increasingly sophisticated platform for precision-guided kidney therapy, supported by monitoring tools that facilitate preclinical evaluation of biodistribution and efficacy. Full article

Global agriculture faces unprecedented challenges, including a projected population of 10 billion by 2050, declining arable land, and the urgent need to phase out antibiotic growth promoters (AGPs) to stem antimicrobial resistance (AMR). This review evaluates fermentation technology as a sustainable solution to the “food–feed–fuel” three competing land uses. We systematically compare solid-state fermentation (SSF) and submerged fermentation (SmF), highlighting their quantitative advantages: SSF offers 2–3× higher volumetric productivity and 70–90% lower water usage for solid wastes (e.g., soybean meal, wheat bran), while SmF provides superior process control for high-value products (e.g., single-cell protein). Key molecular mechanisms are discussed, including enzymatic degradation of anti-nutritional factors (up to 95% phytate and 98.8% tannin removal), mycotoxin detoxification (60–80% reduction), and biosynthesis of bioactive compounds (e.g., vitamin B12 enrichment up to 15-fold). Fermented feeds benefit many livestock species, particularly in organic and high-density farming systems, improving growth performance, gut health, and disease resistance while reducing environmental footprints. Advanced technologies such as AI-driven digital twins, CRISPR-based strain engineering, and precision fermentation are explored to overcome bottlenecks, including heat dissipation, strain stability, and process control. Despite challenges in scale-up, economics, and divergent global regulations (EU, USA, China, Southeast Asia, and Africa), fermentation is a critical biotechnological paradigm for circularity—the circular bioeconomy—and long-term food security. Future research should prioritize cost-effective large-scale implementation and the harmonization of regulatory frameworks. Full article

The achievements of regenerative medicine are based on methods of controlling stem cell division and differentiation. Electromagnetic fields stimulate cell differentiation by means of affecting calcium channels and cellular signaling. However, only a small part of the mechanisms underlying electromagnetic field effect on cells has been studied. The prospect of their use in tissue engineering as an addition or alternative to biochemical effects becomes clear in the course of numerous experiments. Electromagnetic stimulation enhances the effect of biochemical differentiation inducers and can cause the secretion of exosomes of special properties, which may serve as a therapeutic tool. For example, it has been shown that EMFs at 15 Hz and 2 mT increased the expression of chondrogenic differentiation markers SOX9 and COL2 in human bone-marrow MSCs by up to 3-fold (based on Parate et al.). Optimizing EMF parameters (e.g., 15–50 Hz, 1–2 mT) for specific cells and pathologies remains a key challenge of the studies in the field of tissue engineering. This review describes the electromagnetic field effect on the chondrogenic and osteogenic differentiation of MSCs of various origins, which is important for the musculoskeletal tissue recovery, as well as on inflammatory diseases in model animals. Full article

The tendon-to-bone enthesis is a multiphasic structure with four structurally continuous and compositionally distinct regions: tendon, uncalcified fibrocartilage, calcified fibrocartilage and bone. Our study aimed to develop 3D scaffold-free in vitro spheroids and macro-tissues of the enthesis for applications as experimental tools to understand the development and repair of enthesis injury. This study hypothesises that integrating tendon and bone cell spheroids with bone marrow mesenchymal stem cell spheroids will facilitate the production of a fibrocartilaginous interface. 3D Spheroids: The biphasic (tendon–bone) and triphasic co-culture (tendon–stem cell–bone) of spheroids in growth media and chondrogenic media were investigated to establish fusion kinetics, and the cellular and ECM components produced via histology and immunohistochemistry. Complete fusion between spheroids occurred within 6-to-8 days in biphasic co-culture, and 15-to-20 days in triphasic co-culture. Compared to biphasic, the triphasic co-culture in chondrogenic media showed a continuous interface connecting the tendon and bone regions. The presence of collagen I, sulphated proteoglycans and collagen type II in the interface region of triphasic co-culture indicates fibrochondrogenic differentiation. 3D macro-tissues: The modular tissue engineering strategy was used in this study to produce enthesis macro-tissues using spheroids as building blocks. Spheroids were bio-assembled in the triphasic manner (12 tendon spheroids, 12 stem cell spheroids and 8 bone spheroids) in the custom-designed and 3D-printed temporary supports (Formlabs Clear Resin^®) using a customised spheroid bio-assembly system. The fusion of spheroids occurred by day 8 after bio-assembly, and they were removed from temporary supports and cultured in scaffold-free conditions. Although the bio-assembly methodology was successful in producing fused scaffold-free macro-tissues, the histological analysis revealed the presence of an extensive necrotic core due to the large-sized constructs. To conclude, the findings support the hypothesis that a triphasic co-culture has the potential to produce a structurally continuous fibrocartilaginous interface but requires further optimisation to produce macro-tissues with anatomical morphologies and reduced necrotic cores. Full article

Hypoxia and nutrient-deprived microenvironments pose significant challenges to the survival of transplanted human umbilical cord mesenchymal stem cells (UC-MSCs), necessitating the development of controllable oxygen delivery strategies. In this study, we engineered fluorosurfactant-coated oxygen nanobubbles (Tivida^®-stabilized; TONBs) and assessed their cytoprotective effects in a two-dimensional (2D) ischemia-mimetic model (1% O₂ and 1% FBS). The TONBs were characterized by nanoparticle tracking analysis and zeta potential, while dissolved oxygen (DO) release was quantified in DMEM culture media. TONBs formed stable sub-200 nm populations with high colloidal stability (−58 mV) and demonstrated elevated DO levels up to ~18 ppm, compared to DMEM control (~ 8 ppm). Under hypoxic stress, TONB treatment preserved metabolic activity and viability, reduced mitochondrial ROS levels by ~20% and resulted in an ~8–9 fold downregulation of HIF-1α expression relative to untreated hypoxic controls. These results indicate that TONBs provide oxygen buffering to mitigate hypoxia-driven metabolic stress, supporting their potential as an oxygen delivery adjunct for regenerative medicine applications and tissue engineering applications. Full article

Gouty arthritis (GA) is a debilitating autoinflammatory disorder precipitated by the deposition of monosodium urate (MSU) crystals, leading to intense, recurrent joint inflammation and systemic metabolic dysregulation. While hyperuricemia is a prerequisite, the transition to clinical gout involves complex intercellular signaling cascades that are not fully understood. Emerging evidence has identified exosomes,— nanoscale extracellular vesicles, —as critical mediators in this pathological process. Exosomes function as intercellular carriers, transporting a diverse cargo of bioactive molecules, including proteins, lipids, and nucleic acids (e.g., microRNAs), which profoundly influence immune cell activation, inflammasome regulation, and metabolic pathways. This review provides a critical analysis of the dual role of exosomes in both propagating and potentially resolving inflammation in GA. We delve into the intricate mechanisms of exosome-mediated pathogenesis, including the modulation of purine metabolism, lysosomal function, and complement–inflammasome crosstalk. Furthermore, we explore the burgeoning field of exosome-based therapeutics, critically evaluating strategies such as engineered exosomes for targeted drug delivery, mesenchymal stem cell (MSC)-derived exosomes for immunomodulation, and the development of exosomal biomarkers for diagnostics. Additionally, we examine how chemical drugs and herbal compounds may exert therapeutic effects by modulating exosome pathways, offering new insights into integrative treatment approaches. By synthesizing recent findings from proteomic, transcriptomic, and functional studies, we aim to unravel the complexities of exosome signaling in GA and to propose innovative therapeutic avenues that target these pathways to improve patient outcomes. Full article

Stem cells can selectively migrate toward cancer cells, and therapeutic genes can be introduced into stem cells. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells without harming normal cells. In this study, we evaluated the inhibition of tumor growth in castration-resistant prostate cancer (CRPC) using human adipose-derived stem cells (ADSCs) engineered to express cytosine deaminase (CD) and soluble TRAIL (sTRAIL), combined with the prodrug 5-fluorocytosine (5-FC). An immortalized human ADSC line (hTERT-ADSC) was transduced with a lentiviral vector encoding CD and sTRAIL, generating ADSC.CD.sTRAIL cells. Expression of chemoattractant ligands and receptors was assessed by RT-PCR. The suicide gene effect was evaluated by 5-FC treatment, measuring cell viability and apoptosis markers in vitro. A subcutaneous CRPC mouse model was used for in vivo studies. ADSC.CD.sTRAIL cells showed enhanced migration toward prostate cancer cells. Treatment with 5-FC significantly reduced cell viability, and co-culture with PC3 cells plus 5-FC increased apoptosis marker expression. In vivo, mice treated with ADSC.CD.sTRAIL and 5-FC had significantly smaller tumor volumes than control groups, with no treatment-related toxicity observed. These findings suggest that ADSCs overexpressing CD and sTRAIL, combined with 5-FC, effectively inhibit CRPC tumor growth and represent a promising targeted therapeutic strategy. Full article

Chronic liver disease remains a leading cause of global mortality, yet organ shortages and transplant complications limit the efficacy of orthotopic liver transplantation. While extracorporeal support systems serve as temporary bridges, they fail to restore long-term patient autonomy or replicate complex biosynthetic functions. This systematic review, conducted in accordance with PRISMA 2020 guidelines, evaluates recent advancements in implantable artificial livers (IALs) designed for permanent functional integration. We analyzed 71 eligible studies, assessing cellular sources, fabrication strategies, maturation processes, and functional readiness. Our findings indicate significant progress in stem-cell-derived hepatocytes and bioactive scaffolds, such as decellularized extracellular matrix (dECM). However, a critical technological gap remains in scaling current sub-centimeter prototypes toward clinically relevant volumes (~200 mL). Key engineering challenges include integrating hierarchical vascular networks, requiring primary vessels exceeding 2 mm in diameter for surgical anastomosis, and functional biliary systems to prevent cholestatic injury. Furthermore, while micro-vascularization and protein synthesis are well documented, higher-order functions such as spatial zonation and coordinated metabolic stability remain underreported. Future clinical translation necessitates advancements in multi-cellular patterning, microfluidic-driven maturation, and autologous reprogramming. This review provides a comprehensive roadmap for bridging the gap between biofabricated constructs and organ-scale hepatic replacement, emphasizing the need for standardized functional benchmarks to ensure long-term success. Full article

Nonsense-mediated mRNA decay (NMD) is a highly conserved RNA quality and quantity surveillance machinery in eukaryotic cells, serving as an important node in the post-transcriptional gene expression. Previous studies using the complete knockout of individual NMD factors in cells or animals reveal that NMD deficiency causes developmental defects and compromises tissue homeostasis. However, because most NMD factors participate in multiple molecular functions, a direct link between NMD and cell fate determination is missing. SMG6 is a core NMD effector and the only endoribonuclease among all NMD factors. The NMD function of SMG6 is exclusively mediated by its PIN (PilT N-terminus) domain. In this study, we engineered a mouse model with the capability of specifically deactivating the SMG6’s PIN domain/endoribonuclease activity (Smg6-PIN^F/F), but not knocking out the complete SMG6 protein. We found that SMG6’s PIN domain is essential for NMD activity in embryonic stem cells (ESCs) and various tissues of adult mice. Furthermore, loss of SMG6’s PIN domain is dispensable for the mouse ESC self-renewal, but severely compromises the differentiation, which consequently causes the mutant mice to die during the process of organogenesis. Through the induced deletion of SMG6’s PIN domain in adult mice, we found that loss of SMG6’s NMD function affects the homeostasis of several mouse tissues, including the testis and the intestine. In sum, our study establishes a mechanistic link between NMD per se and cell fate determination of mouse ESCs, as well as in the tissues of adult mice, where cell fate transitions are actively ongoing. The Smg6-PIN^F/F mouse line could be a valuable strain for elucidating the biology of NMD per se. Full article

Kidney organoids, as three-dimensional microstructures derived from human pluripotent stem cells or adult stem cells, precisely simulate the cellular heterogeneity, spatial conformation, and some physiological functions of human kidney units in vitro. Kidney organoids are three-dimensional microstructures derived from human pluripotent stem cells (hPSCs). They precisely simulate the cellular heterogeneity, spatial conformation, and key physiological functions of human kidney units in vitro. This technology, by replicating the interaction network between the glomerulus and renal tubules, provides an unprecedented window for observing the dynamic development and pathological processes of human kidneys. This technology replicates the interaction network between the glomerulus and renal tubules. It thereby provides an unprecedented window into human kidney development and disease. Based on the strong similarity between organoids and native organs, as well as the human genetic information they carry, both iPSC-derived and patient-specific organoids have demonstrated significant value in kidney disease modeling, drug toxicity testing, and the development of regenerative treatment strategies. This review systematically elucidates the key advancements in the field of kidney organoids, including optimized strategies for stem cell-directed differentiation, innovations in culture systems driven by biomaterials engineering, technological breakthroughs in disease model construction, and applications of organoids in drug screening platforms and regenerative medicine. Additionally, it analyzes translational challenges such as the lack of vascularization, insufficient functional maturity, and obstacles in standardized production. These insights will deepen the understanding of kidney pathological mechanisms and propel organoid technology towards substantial clinical therapeutic applications. This review summarizes how convergent technologies in stem cell biology and bioengineering aim to bridge this functional gap. We examine the use of advanced organoids in disease modeling and drug discovery. We also highlight their current limitations. Our focus is on the core translational bottlenecks: vascularization, long-term maturation, and scalable production. Overcoming these hurdles is essential to transform kidney organoids from a research tool into a platform for precision medicine and regenerative therapy. Full article

Temporomandibular joint (TMJ) disorders represent chronic degenerative musculoskeletal conditions with a high prevalence in the general population and limited regenerative treatment options. Owing to the insufficient efficacy of current conservative and surgical therapies, there is a growing clinical need for biologically based regenerative approaches. Tissue engineering (TE), particularly scaffold-based strategies, has emerged as a promising avenue for TMJ regeneration. This systematic review analyzed preclinical in vivo studies investigating scaffold-based interventions for TMJ disc and osteochondral repair. A structured literature search of PubMed and Scopus databases identified 39 eligible studies. Extracted data included scaffold composition, use of cellular and bioactive components, animal models, and reported histological, radiological, and functional outcomes. Natural scaffolds, such as decellularized extracellular matrix and collagen-based hydrogels, demonstrated favorable biocompatibility and support for fibrocartilaginous regeneration, whereas synthetic materials including polycaprolactone, poly (lactic-co-glycolic acid), and polyvinyl alcohol provided superior mechanical stability and structural tunability. Cells were used in 17/39 studies (43%); quantitative improvements were variably reported across these studies. Bioactive molecule delivery, including transforming growth factor-β, histatin-1, and platelet-rich plasma, further enhanced tissue regeneration, while emerging drug- and gene-delivery approaches showed potential for modulating local inflammation. Despite encouraging results, the reviewed studies exhibited substantial heterogeneity in experimental design, outcome measures, and animal models, limiting direct comparison and translational interpretation. Scaffold-based approaches show preclinical promise but heterogeneity in design and incomplete quantitative reporting limit definitive conclusions. Future research should emphasize standardized methodologies, long-term functional evaluation, and the use of clinically relevant large-animal models to facilitate translation toward clinical application. However, functional and biomechanical outcomes were inconsistently reported and rarely standardized, preventing robust conclusions regarding the relationship between structural regeneration and restoration of TMJ function. Full article