World journal of stem cells最新文献

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.

Tendon and ligament injuries represent a major orthopedic challenge with limited effective regenerative options. In an original research study by Yang et al 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 in vitro. This editorial contextualizes their findings within the broader field of ligament regeneration and highlights the translational potential of their strategy.

[This corrects the article on p. 1077 in vol. 15, PMID: 38179214.].

Background: 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.

Aim: To investigate how the exosomes released by stem cells and/or EXE can promote cardiac repair and improve isoproterenol (ISO)-induced post-ischemic hypertrophy.

Methods: The enrolled animals were divided into 8 control rats and 32 experimental rats. Induction of MI was performed using ISO. Then, the experimental rats were divided into 4 groups: Rats subjected to 4 weeks of swimming EXE, rats treated with exosomes, and the combined treatment. Additionally, functional and interactional exploration of targeted proteins was conducted using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and STRING database, along with histological examination.

Results: Both MSC-EXO or EXE significantly improved ISO induced elevation of cardiac enzymes, oxidative stress, and inflammatory markers, as well as the degenerative changes of the cardiac muscles, fibrosis, and apoptosis. Meanwhile, the combined treatment of EXE and MSC-EXO resulted in a significant improvement in cardiac function and structure as compared to all groups that synchronized with dual inhibition of extracellular signal-regulated kinase and protein kinase B/mammalian target of rapamycin (P < 0.01) signaling and modulation of matrix metalloproteinase 9 and sarcoplasmic endoplasmic reticulum calcium ATPase type 2a, with significant improved angiogenesis.

Conclusion: Functional and structural cardiac improvements are accompanied by reduced inflammation, oxidative stress, and apoptosis. Both MSC-EXO and EXE exert cardio-protection by upregulating sarcoplasmic endoplasmic reticulum calcium ATPase, the critical pump for normal calcium handling.

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.

Background: 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.

Aim: To study the biological effects of MSC-EVs in regulating cellular senescence.

Methods: In this study, we developed a clinical-grade production process for MSC-EVs and defined the release criteria for products suitable for human use. To support the clinical use of our product as a therapeutic agent, we performed efficacy assays to evaluate the anti-aging capacity of MSC-EVs in vitro and in vivo.

Results: The functional analysis results revealed that MSC-EVs significantly reduced the levels of senescence-associated β-galactosidase, matrix metallopeptidase 1, P21, and interleukin-1β and increased the level of collagen I in a naturally aged cell model of human dermal fibroblasts. Similarly, treatment with MSC-EVs effectively improved D-gal-induced subacute aging in mice, aging-related histopathological changes, oxidative stress, and aging-related gene expression.

Conclusion: These findings indicate that MSC-EVs can partially alleviate D-gal-induced senescence by reducing oxidative stress and regulating metabolism. Overall, these findings strongly suggest that MSC-EVs hold promise for aging therapy.

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 via 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.

Background: 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.

Aim: To compare the functional differences between CD146+ and CD146- MSCs and investigate the underlying mechanisms.

Methods: In this study, magnetic beads were used to sort umbilical cord-derived MSCs into CD146+ and CD146- subsets. The pro-angiogenic factors (hepatocyte growth factor, prostaglandin E2, vascular endothelial growth factor, angiopoietin-1) production and immunomodulatory effects on T lymphocyte subsets were evaluated in vitro. The therapeutic efficacy was assessed in an acute respiratory distress syndrome (ARDS) mouse model via tail vein injection.

Results: Cytokine secretion and angiogenesis: CD146+ MSCs significantly increased the production of hepatocyte growth factor, prostaglandin E2, vascular endothelial growth factor, and angiopoietin-1 and exhibited increased pro-angiogenic activity in vitro. Immunomodulatory effects: CD146+ MSCs potently inhibited the differentiation and proliferation of pro-inflammatory T helper type 1/T helper type 17 cells while promoting the expansion of regulatory T cells during T lymphocyte activation. ARDS therapy: In a mouse ARDS model, compared with CD146- MSCs, CD146+ MSCs demonstrated superior therapeutic efficacy, as evidenced by improved clinical scores. Mechanistically, CD146+ MSCs activated the nuclear factor kappa B pathway, upregulated cyclooxygenase 2 expression, and facilitated damaged epithelial cell repair.

Conclusion: CD146+ MSCs show stronger ARDS therapeutic potential than CD146- MSCs via pro-angiogenic/immunomodulatory traits. Nuclear factor kappa B/cyclooxygenase 2 activation aids epithelial repair, highlighting CD146+ MSCs as promising targets.