Correction to "ADSC-Exos outperform BMSC-Exos in alleviating hydrostatic pressure-induced injury to retinal ganglion cells by upregulating nerve growth factors"
[This corrects the article on p. 1077 in vol. 15, PMID: 38179214.].
Sclerostin-silenced human umbilical cord mesenchymal stem cells ameliorate bone metabolism in steroid-induced femoral head necrosis
Steroid-induced avascular necrosis of the femoral head (SANFH) involves bone metabolism imbalance and lacks effective therapies. Mesenchymal stem cells (MSCs), particularly human umbilical cord MSCs (hUCMSCs), offer promise due to their osteogenic and immunomodulatory potential. Sclerostin () inhibits bone formation, so we developed a multi-target gene silencing strategy against using RNA interference. We created hUCMSCs with -silenced (sh-hUCMSCs) and compared their therapeutic efficacy with unmodified hUCMSCs in SANFH mice. This study explores a novel approach to enhance osteogenesis and mitigate SANFH progression.
Mesenchymal stem-derived exosomes enhance therapeutic benefits of exercise in isoproterenol-induced myocardial ischemia: Targeting ERK and Akt/mTOR signaling
Myocardial infarction (MI) is a significant global cause of chronic heart failure. In post-ischemic cardiac hypertrophy, multiple molecular targets and signals within the cardiac tissue are evident. Mesenchymal stem cell-derived exosomes (MSC-EXO) and exercise (EXE) showed promise in enhancing post-ischemic cardiac repair.
Efficacy of extracellular vesicles derived from mesenchymal stromal cells in regulating senescence: and insights
Extracellular vesicles derived from mesenchymal stromal cells (MSC-EVs) can be used for anti-aging therapy and treating various aging-related diseases. However, the clinical application of MSC-EVs is still limited, mainly due to insufficient information on the preparation process, quality, and mechanism of action of MSC-EVs.
Melanoma cell adhesion molecule-positive mesenchymal stromal cells alleviate acute respiratory distress syndrome nuclear factor kappa-B-mediated paracrine regulation
Mesenchymal stromal cells (MSCs) are renowned for their immunosuppressive properties, which make them widely used in managing excessive inflammation. Although CD146+ and CD146- MSCs exhibit similar morphological traits and surface marker expression levels, the specific characteristics and differential regulatory mechanisms of these two subtypes remain poorly understood. This knowledge gap has limited the precise application of MSCs in targeted therapeutic strategies.
Synovial mesenchymal stem cell-derived exosomes delivering GRPEL1 activate PINK1-mediated mitophagy to promote cartilage repair in arthritis
Osteoarthritis (OA) remains a challenging degenerative joint disease with limited therapeutic interventions.
Recombinant human thrombopoietin in pediatric allogeneic hematopoietic stem cell transplantation: Clinical insights and future directions
The cohort study by Li provides timely and clinically relevant evidence on the use of recombinant human thrombopoietin (rhTPO) in pediatric allogeneic hematopoietic stem cell transplantation. The authors report enhanced platelet engraftment and a favorable safety profile, particularly in younger children aged 0-9 years. This age-dependent difference not only highlights the physiological responsiveness of early hematopoietic environments to rhTPO but also raises important questions about tailoring supportive therapies across pediatric age groups. While the findings are promising, the lack of a control group and single-center limitations warrant further multicenter, long-term investigations. Nevertheless, the study lays a compelling foundation for integrating rhTPO more broadly into pediatric transplant protocols and for advancing individualized post-transplant care.
Silent saboteurs: How microplastics disrupt stem cells and tissue regeneration
Microplastics (MPs), defined as plastic particles with diameters less than 5 mm, have become significant global environmental contaminants. MPs accumulate in human tissues and organs, raising significant concerns about their potential biological toxicity. Evidence indicates that MPs and associated toxins disrupt stem cell self-renewal, proliferation, and differentiation processes essential for tissue regeneration and systemic homeostasis, yet research on MP-induced stem cell damage remains limited. To identify relevant and recent studies, we searched the PubMed database using title and abstract fields. This review synthesizes current evidence across organ systems, including nervous, hematopoietic, skeletal, and urinary systems, to systematically categorize phenotypic disruptions and underlying mechanisms in stem cells. We further evaluate the utility of stem-cell-derived organoids in modeling organ-specific MP toxicity. By consolidating fragmented findings, this work provides a critical framework for assessing MP risks to tissue regeneration and informs strategies for regenerative medicine and public health protection.
Engineering ligament tissues: Synergistic power of aligned nanofibers and cyclic stretch
Tendon and ligament injuries represent a major orthopedic challenge with limited effective regenerative options. In an original research study by Yang developed a tissue engineering approach combining aligned nanofiber scaffolds with cyclic uniaxial stretching to promote tenogenic differentiation in bone marrow-derived mesenchymal stem cells. Their results provide critical insight into how structural and mechanical cues can synergize to generate ligament-like tissue . This editorial contextualizes their findings within the broader field of ligament regeneration and highlights the translational potential of their strategy.
Extracellular vesicles from adipose-derived stem cells in bone regeneration: Mechanisms and therapeutic advances
Extracellular vesicles (EVs) secreted by adipose-derived stem cells (ADSCs) have emerged as a promising cell-free therapeutic tool for bone regeneration. These EVs deliver a diverse array of bioactive molecules, including proteins, lipids, and nucleic acids, thereby modulating the bone microenvironment, activating key signaling pathways, and promoting bone regeneration. Innovative strategies involving preconditioning, genetic modification, and biomaterial-assisted delivery have been explored, with preclinical studies demonstrating synergistic effects that enhance targeting specificity and therapeutic efficacy. Functionally, EVs derived from ADSCs promote osteogenesis by enhancing osteoblast and mesenchymal stem cell activity, support angiogenesis through vascular endothelial growth factor signaling, and modulate inflammation by shifting macrophages from pro-inflammatory to anti-inflammatory phenotypes. In disease-specific contexts, they reduce cartilage degradation and support subchondral bone restoration in osteoarthritis, while in osteoporosis, they help restore the balance between bone formation and resorption and mitigate bone loss. Despite these promising developments, challenges remain in standardizing production protocols, optimizing delivery systems, and confirming long-term safety and efficacy in clinical settings. This review summarizes current insights into the mechanisms of EVs derived from ADSCs in bone-related diseases and highlights recent innovations and future directions that may accelerate their clinical application as a regenerative therapy.
Mesenchymal stem cell-derived microRNAs: Key immunomodulators to prevent ocular tissue degeneration
MicroRNAs (miRNAs) are small non-coding RNAs of 20-22 nucleotides in length. They have been identified as major regulators in the secretome of mesenchymal stem cells (MSCs) including adipose tissue, bone marrow, Wharton's jelly, and dental pulp. These MSCs and their secretome with specific miRNAs are known modulators of the immune response, angiogenesis, inflammation, and apoptosis. In this review, the application of MSC-derived miRNAs in treating several ocular conditions including dry eye, glaucoma, and retinal degenerative diseases has been compiled. In addition, the emerging role of MSC-derived extracellular vesicles carrying miRNAs as a major cargo, regulating the target cells in the human eye has been reviewed. Finally, the bioengineering of nanovesicles with specific MSC-derived miRNAs as novel drug therapy has been discussed.
Living bio-drug therapies using mesenchymal stem cells and exosomes for mechanically ventilated patients with acute respiratory distress syndrome: A systematic review and meta-analysis
Mesenchymal stem cells (MSCs), as a living bio-drug, are being considered as a potential treatment for coronavirus disease 2019 (COVID-19)-induced acute respiratory distress syndrome (ARDS) due to their immunomodulatory and reparative properties.
Role of mesenchymal stem cell-derived exosomal non-coding RNAs in bone and bone-related disorders
Mesenchymal stem cells (MSCs) are known for their ability to differentiate into various cell lineages, including osteoblasts (bone-forming cells), and for their significant paracrine effects. Among their secreted products, exosomes have gained considerable attention as nanoscale carriers of bioactive molecules such as non-coding RNAs (ncRNAs). These ncRNAs, including microRNAs, long ncRNAs, and circular ncRNAs, are critical regulators of gene expression and cellular functions. Moreover, MSC-derived exosomes not only offer advantages such as targeted delivery, reduced immunogenicity, and protection of cargo material, but also carry ncRNAs that have therapeutic and diagnostic potential in bone-related disorders. Emerging evidence has highlighted the role of MSC-derived exosomal ncRNAs in osteogenesis, bone remodeling, and intercellular signaling in the bone microenvironment. This review consolidates recent research on the role of MSC-derived exosomal ncRNAs in maintaining bone homeostasis and bone-related disorders various signaling pathways and epigenetic modifications. Furthermore, we explore the therapeutic potential of MSC-derived exosomal ncRNAs as biomarkers and therapeutic targets. This comprehensive review offers key insights into the regulatory roles of MSC-derived exosomal ncRNAs in bone biology and their clinical significance in bone-related diseases.
Long-term follow-up of autologous nasal epithelial stem cell transplantation for congenital olfactory disorders in children
Congenital olfactory disorders (CODs) are rare but impactful conditions that impair the sense of smell from birth. These disorders can significantly affect a child's appetite, nutrition, safety awareness, and overall quality of life. Despite their clinical importance, treatment options for CODs remain limited and largely ineffective, with no established therapies capable of restoring olfactory function in pediatric patients. Recent advances in regenerative medicine and stem cell therapy offer promising avenues for addressing sensory deficits. Nasal epithelial stem cells have emerged as a viable candidate for therapeutic intervention due to their accessibility and intrinsic ability to differentiate into olfactory sensory neurons. Preliminary studies suggest their potential in promoting the regeneration of the olfactory epithelium and functional recovery. However, long-term data on the efficacy and safety of such approaches in children are lacking.
Neural crest-derived mesenchymal stem cells: Fates and perspectives
Neural crest-derived mesenchymal stem cells (NC-MSCs) represent a unique population with remarkable regenerative potential, owing to their embryonic origin and exceptional differentiation capacity. These cells demonstrate superior performance in neural and craniofacial tissue regeneration compared to conventional mesenchymal stem cells, with dental stem cells emerging as particularly promising candidates for clinical applications in periodontics and endodontics. Despite their therapeutic promise, adult NC-MSCs face significant challenges including donor site limitations, cellular heterogeneity, and scalability issues. Recent advances in pluripotent stem cell offer potential solutions through the generation of NC-MSCs , though safety concerns regarding tumorigenicity and long-term stability remain to be addressed through comprehensive preclinical studies. This review provides a comprehensive analysis of NC-MSC biology, highlighting their developmental origins, molecular characteristics, and current applications in regenerative medicine. We critically evaluate existing challenges and future directions, emphasizing the need for standardized protocols, improved characterization methods, and rigorous preclinical evaluation to facilitate clinical translation and therapeutic implementation.
Human umbilical cord mesenchymal stromal cell-derived extracellular vesicles alleviate radiation induced pulmonary fibrosis
Pulmonary fibrosis, a chronic, fatal lung disease affecting millions worldwide, urgently needs more effective treatments. This article comments on the study by Wang , which proposed that human umbilical cord mesenchymal stromal cell-derived exosomes alleviate rats radiation induced pulmonary fibrosis. The study demonstrated that these exosomes suppressed inflammation, extracellular matrix deposition, and epithelial-mesenchymal transition by inhibition of AKT signaling in radiation-exposed alveolar epithelial cells. Despite these observations, aspects of the study merit further discussion. Most importantly, further confirmation is needed to prove that the therapeutic effect is exerted through the AKT signaling pathway. Moreover, the definitions of both mesenchymal stem cell and exosomes require further refinement, more rigorous terms should be mesenchymal stromal cell and extracellular vesicles. It seems apparent that this therapy will develop into one of great clinical value.
Wumei Pills enhance intestinal stem cell - mediated repair in chemotherapy-induced mucositis - dependent modulation of the gut microbiota
Intestinal mucositis is a severe and common complication of chemotherapy, characterized by disruption of the gut microbiota, intestinal inflammation, and epithelial barrier damage. Intestinal stem cells (ISCs) are essential for epithelial renewal and barrier maintenance, yet chemotherapy impairs ISC proliferation and function, delaying mucosal repair. We hypothesized that Wumei Pills (WMP) could protect against chemotherapy-induced intestinal mucositis by modulating gut microbiota - particularly () - to restore ISC activity, preserve microbial balance, reduce inflammation, and promote epithelial regeneration.
Post-translational modifications in osteogenic differentiation of oral-derived stem cells: Mechanisms and clinical implications
Osteogenesis is driven by the differentiation of osteoblasts and the mineralization of the bone matrix, with oral-derived stem cells playing a significant role in this process. Various post-translational modifications (PTMs), such as phosphorylation, acetylation, methylation, and glycosylation, regulate osteogenic differentiation (OD). These modifications influence the expression of osteogenic genes by modulating the activity of key transcription factors like runt-related transcription factor 2 and osterix. While the molecular mechanisms behind OD are increasingly understood, many questions remain, particularly regarding how PTMs control the specificity and efficiency of stem cell differentiation. Recent research into these modifications has underscored the potential of stem cell therapy for bone regeneration and treating bone-related diseases. This review summarizes the role of PTMs in the OD of oral-derived stem cells, discusses their clinical applications, and suggests future research directions.
HOX and MEINOX in cellular plasticity, fibrosis, and cancer
HOX transcription factors and their cofactors, MEINOX, are critical regulators of positional identity and cellular plasticity. While their functions are essential during embryonic development, they also play key roles in maintaining adult tissue homeostasis. Dysregulation of and has been implicated in the pathogenesis of various diseases, including fibrosis and cancer. This review explores the contributions of HOX and MEINOX to dedifferentiation and cellular reprogramming, processes that drive fibrotic disease onset and cancer progression. It also addresses their role in extracellular matrix remodeling in these conditions. Particular attention is given to their involvement in epithelial-mesenchymal transition, where altered and expression promotes phenotypic plasticity, cancer invasiveness, and fibrotic tissue remodeling. By integrating these perspectives, this review underscores the significance of dysregulation and altered positional identity in disease progression. Targeting this dysregulation may offer innovative strategies to modulate epithelial-mesenchymal transition and extracellular matrix dynamics, presenting new therapeutic opportunities for combating fibrosis and cancer.
Exploring the critical therapeutic window: Dose-frequency optimization of human umbilical cord mesenchymal stem cells for preclinical asthma treatment
Current drugs primarily target inflammation control but do not reverse tissue remodeling changes for asthma. Human mesenchymal stem cells are known for their anti-inflammatory and tissue remodeling capabilities. However, limited research has explored the therapeutic impact of varying doses and frequencies of human umbilical cord blood-derived mesenchymal stem cells (HUC-MSCs) on established airway remodeling in experimental asthma.
Dual role and clinical application of extracellular vesicles in acute respiratory distress syndrome: Mechanism analysis and translational challenges
Acute respiratory distress syndrome (ARDS) is a severe and life-threatening manifestation of acute lung injury, characterized by widespread pulmonary inflammation and edema, ultimately resulting in acute respiratory failure. Despite advancements in mechanical ventilation and lung-protective strategies, targeted therapies aimed at modulating dysregulated inflammation and promoting tissue repair remain elusive. Extracellular vesicles (EVs), critical mediators of intercellular communication, have emerged as a promising research focus due to their dual regulatory roles in ARDS pathogenesis. Pro-inflammatory EVs, derived from pathogens or injury-stressed cells, exacerbate alveolar macrophage activation and increase endothelial permeability, thereby aggravating pulmonary damage. In contrast, anti-inflammatory EVs originating from mesenchymal stem cells facilitate alveolar barrier restoration and tissue repair by delivering reparative molecular cargo. This review systematically evaluates the dualistic functions of EVs in ARDS from three key perspectives: Molecular mechanisms, clinical translation, and technical challenges. We further discuss the complexities associated with EV heterogeneity, pathogen interactions, and standardization in EV production. Additionally, we propose future directions that integrate engineered EV modifications and multi-omics approaches to address current therapeutic limitations and enhance ARDS management.
