Stem Cell Research & Therapy最新文献

{"title":"Mitochondria: the key hub for hematopoietic stem cell homeostasis maintenance and fate determination.","authors":"Ran Xu, Yaowei Meng, Anyu Xu, Xiaoming Yang, Weiming Tian, Changyan Li","doi":"10.1186/s13287-026-05183-2","DOIUrl":"10.1186/s13287-026-05183-2","url":null,"abstract":"<p><p>Hematopoietic stem cells (HSCs) constitute the pivotal cellular subset sustaining long-term hematopoietic homeostasis, characterized by robust self‑renewal and multilineage differentiation potential. Under physiological conditions, HSCs undergo stepwise differentiation through rigorously controlled regulatory networks to produce a full repertoire of mature blood cells, fulfilling basal physiological demands. Upon exposure to stress or pathological insults (e.g., bone marrow niche dysregulation), HSCs rapidly activate emergency regenerative programs to reconstitute hematopoietic function and restore systemic homeostasis. As intracellular \"powerhouses\" and central hubs of metabolic regulation, mitochondria exert profound regulatory effects on HSCs fate determination. The dynamic balance of mitochondrial metabolism not only furnishes HSCs with sufficient bioenergy but also generates critical metabolic intermediates; meanwhile, the fine-tuning of oxidative stress and autophagic machinery ensures mitochondrial network integrity. These biological processes are intricately intertwined, forming a complex regulatory network that profoundly modulates HSCs self-renewal, lineage commitment, and long-term hematopoietic reconstitution potential. This review systematically dissects the multi-dimensional regulatory mechanisms by which mitochondria govern HSCs, elaborates on the synergistic interactions and antagonistic effects among distinct components of the regulatory circuitry, and defines the pivotal role of mitochondria in sustaining HSCs homeostasis and orchestrating their repair responses to cellular damage. This work establishes a novel theoretical framework for devising mitochondrial-targeted interventions to sustain metabolic homeostasis in HSCs. Furthermore, it lays a solid scientific foundation for the treatment of hematological diseases and the development of precision therapeutic strategies, offering new insights into the clinical management of hematopoietic disorders.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low frequency sinusoidal electromagnetic field accelerating intervertebral fusion through YAP/β-catenin axis.","authors":"Guangzi Chen, A Chunpin, Tao Xu, Jian Li, Weigang Li, Delu Zeng, Li Huang, Xuan Fang, Gaohong Sheng, Hongqi Zhao, Chaoxu Liu","doi":"10.1186/s13287-026-05137-8","DOIUrl":"10.1186/s13287-026-05137-8","url":null,"abstract":"<p><strong>Objective: </strong>Lumbar interbody fusion plays a crucial role in treating lumbar degenerative diseases, but its fusion rate is influenced by various factors. As a non-invasive physical therapy, low-frequency sinusoidal electromagnetic fields have been proven to promote bone tissue regeneration, although the specific molecular mechanisms remain incompletely understood. The aim of this study is to investigate whether low-frequency sinusoidal electromagnetic fields (LF-SEMF) can regulate the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts through YAP/β-catenin axis in vitro, and to evaluate the effect of LF-SEMF in assisting HA/Col I composite scaffold loaded with BMSCs in intervertebral fusion.</p><p><strong>Methods: </strong>The impact of LF-SEMF on osteogenic differentiation and mineralization was studied using BMSCs through alkaline phosphatase (ALP) staining and Alizarin red staining. Techniques such as Western blot, immunofluorescence, and qRT-PCR were employed to detect the impact of LF-SEMF on the YAP/β-catenin signaling pathway and related osteogenic genes. Gene silencing was performed to validate the critical role of the YAP/β-catenin axis in the promotion of osteogenic differentiation by LF-SEMF. A rat intervertebral fusion model was established, and the effects of LF-SEMF on intervertebral fusion were evaluated using imaging techniques (X-ray, Micro-CT) and histological analysis (HE staining, Masson staining, and immunohistochemical staining).</p><p><strong>Results: </strong>In vitro experiments demonstrated that exposure to LF-SEMF could facilitate the osteogenic differentiation of BMSCs, significantly upregulating the protein expression levels of YAP and β-catenin, and enhancing the expression of osteogenesis-related genes. Gene silencing experiments confirmed that the YAP/β-catenin axis played a critical role in the promotion of osteogenic differentiation by LF-SEMF. Additionally, animal studies showed that LF-SEMF could significantly promote new bone formation and increase bone strength in the fusion region of caudal vertebrae, while inhibition of YAP/β-catenin signaling pathway attenuated the fusion effect.</p><p><strong>Conclusions: </strong>LF-SEMF promotes the differentiation of bone marrow mesenchymal stem cells into osteoblasts through YAP/β-catenin signaling pathway. The hydroxyapatite/collagen I composite scaffold loaded with bone marrow mesenchymal stem cells can effectively improve the fusion effect of caudal vertebral fusion by LF-SEMF.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-derived decidual organoids reveal rhG-CSF-associated protective responses involving JAK2/STAT3 signaling in recurrent spontaneous abortion.","authors":"Changqiang Wei, Xuemei Tan, Yiyun Wei, Jinlian Cheng, Zhuolin Zhou, Wenmei Yang, Yulu Zeng, Wenyao Jing, Xiangyun Zhu, Lihong Pang","doi":"10.1186/s13287-026-05187-y","DOIUrl":"10.1186/s13287-026-05187-y","url":null,"abstract":"<p><strong>Background: </strong>Recurrent spontaneous abortion (RSA) is a complex reproductive disorder frequently lacks effective therapeutic interventions. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) has shown promise in improving pregnancy outcomes in RSA, but its underlying mechanisms remain unclear. Organoid technology offers new opportunities for disease modeling and mechanistic research in reproductive medicine.</p><p><strong>Methods: </strong>Decidual tissue samples from RSA patients were utilized to establish decidual organoids using three-dimensional (3D) culture techniques. These organoids were characterized via morphological observation, hematoxylin and eosin (H&E) and Periodic Acid-Schiff (PAS) staining, immunofluorescence, and immunohistochemistry to validate key marker expression and hormone responsiveness. The effects of rhG-CSF on organoid viability were evaluated using luminescence assays. Transcriptomic sequencing and bioinformatics analyses were performed to identify differentially expressed genes and pathways following rhG-CSF stimulation. Protein expression and signaling pathway activation were further assessed via Western blot analysis.</p><p><strong>Results: </strong>Decidual organoids were successfully established and recapitulated the structural and functional features of primary tissue, including hormone responsiveness and marker expression. rhG-CSF significantly promoted organoid proliferation, enhanced anti-apoptotic and angiogenic capacity, and induced inflammatory responses. Transcriptomic and pathway analyses indicated an enrichment and activation of the JAK2/STAT3 signaling pathway following rhG-CSF treatment. Western blot indicated increased phosphorylation of JAK2 and STAT3, upregulation of PCNA, VEGFA, IL-1β, IL-6, and Bcl-2, and downregulation of Bax in response to rhG-CSF.</p><p><strong>Conclusion: </strong>A patient-derived decidual organoid model was established and validated to recapitulate in vivo tissue characteristics. In this in vitro RSA model, rhG-CSF appeared to exert protective effects by promoting proliferation, inhibiting apoptosis, and enhancing angiogenesis-responses that are potentially associated with the activation of JAK2/STAT3 signaling. These findings provide new insights and experimental evidence that may inform future RSA treatment strategies.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomimetic scaffolds based on stem cells for neural tissue engineering: a review.","authors":"Somayeh Kakehbaraei, Cyrus Jalili, Amin Bahreini, Touraj Zamir Nasta, Seyran Kakebaraei, Morteza Arab-Zozani","doi":"10.1186/s13287-026-05182-3","DOIUrl":"10.1186/s13287-026-05182-3","url":null,"abstract":"<p><p>Implementing biomaterials, scaffolds, and stem cell therapy for neural tissue regeneration introduces a revolutionary strategy in regenerative healthcare. By embedding stem cells within intricately engineered scaffolds that replicate the natural extracellular matrix (ECM), remarkable advancements in patient well-being can be realized. These biomimetic scaffolds not only emulate native tissues; they also possess a dynamic, multidimensional structure. Their biocompatibility and capacity to influence cellular metabolism position them as exceptional platforms for bioengineering. The outstanding flexibility of this technique enables optimal selection of biomaterials, scaffold designs, cells, and inorganic materials. A formidable body of evidence is emerging to highlight the vast potential of biomimetic scaffolds in tissue engineering and personalized medicine. Recent scientific studies reveal a significant rise in in vivo testing of biomimetic scaffold-based products, highlighting the critical importance of this research domain and the pressing necessity for continued exploration to facilitate the safe advancement of human-compatible biomimetic tissues and organs. This comprehensive analysis illuminates the vital conditions, challenges, and exciting innovations in scaffold design, especially in the context of brain tissue engineering. Ultimately, this review formulates a comprehensive framework for generating scaffolds that incorporate biomimetic attributes and optimal structures. The innovation of brain-implantable scaffolds holds great promise for reducing the impact of neurological disorders (ND).</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving stem cell-derived extracellular vesicles for better tendon and tendon-to-bone junction regeneration: strategies and future directions.","authors":"Haining Liu, Pauline Po Yee Lui","doi":"10.1186/s13287-026-05171-6","DOIUrl":"10.1186/s13287-026-05171-6","url":null,"abstract":"<p><p>Chronic tendinopathy is a debilitating tendon overuse disorder characterized by localized tenderness, swelling, and pain, significantly impairing physical function. It is particularly common among the overuse and aging populations. Traditional treatment options, including conservative therapies and surgical interventions, often yield limited success. Recent studies indicate that extracellular vesicles (EV) derived from stem cells provide a promising therapeutic avenue for healing of tendon and tendon-to-bone junction (TBJ) injuries associated with chronic tendinopathy. Their unique properties, such as higher cargo stability and the ability to serve as carriers for targeted drug delivery, position them as ideal candidates for tendinopathy treatment. However, the low yield of EVs presents challenges for clinical applications. This review systematically review various strategies to enhance EV yield and function, including preconditioning stem cells through biophysical, biological, or chemical means; genetic engineering of stem cells; in vitro loading of proteins or drugs and surface modification of EVs; and modifying the stem cell culture environment, particularly through three-dimensional (3D) culture techniques. Emphasis is placed on scaffold-free methods, scaffold-based methods, 3D printing, spinner flasks, and bioreactors, which can potentially improve EV yield and functions for tendon and TBJ regeneration. The review also summarizes relevant preclinical data and explores the molecular mechanisms underlying enhanced EV yield and functions, as well as the mechanisms of EVs on tendon and TBJ repair. Future research directions include investigating various EV enhancement strategies in models of degenerative tendon injury, studying the underlying molecular mechanisms, establishing cost-effective methods for scalable EV production, optimizing EV treatment protocols for clinical translation, and exploring combination strategies to enhance therapeutic EV production and function.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A non-invasive, patient-derived organoid platform from uterine lavage fluid for modeling endometrial implantation and disease.","authors":"Huiyu Qiu, Zhiwen Fan, Di Liu, Li Deng, Xiaoxia Wang, Yuanyuan Yang, Tianli Yang, Fen Tian, Jie Hao, Qiong Zhang, Bin Xu, Jing Fu, Huiling Ni, Yinshuang Li, Hankun Su, Fen Xiao, Yuanyuan Sun, Jingjing Chen, Zhiying Duan, Jing Zhao, Hui Li, Yanping Li","doi":"10.1186/s13287-026-05166-3","DOIUrl":"10.1186/s13287-026-05166-3","url":null,"abstract":"<p><strong>Background: </strong>Endometrial organoids, with their three-dimensional structure and robust hormonal responsiveness, have emerged as valuable models for investigating uterine physiology and embryo implantation. However, conventional derivation from endometrial biopsies is invasive, carries surgical risks, and limits repeated sampling. This study introduces uterine lavage fluid as a non-invasive source for generating endometrial organoids.</p><p><strong>Methods: </strong>We established endometrial organoids from uterine lavage fluid (UF-EOs) and compared them with matched tissue-derived endometrial organoids (T-EOs) for morphology, proliferation, epithelial marker expression, transcriptomic profiles, and hormone responsiveness. Lavage fluid was collected from reproductive-age women with normal endometrium and from patients with intrauterine adhesions (IUA). Differential gene-expression analysis between IUA-derived and control organoids was performed to identify IUA-associated signatures. A microinjection platform was developed to deliver HTR8/SVneo trophoblast spheroids into the organoid lumen.</p><p><strong>Results: </strong>UF-EOs were successfully derived from 90% of control individuals (9/10) and 60% of IUA patients (6/10). UF-EOs and T-EOs were morphologically indistinguishable, with comparable proliferation rates (104.6 ± 6.21 versus 106.4 ± 5.16; P > 0.05) and equivalent expression of epithelial markers (EpCAM, Cytokeratin 7, E-cadherin). Transcriptomic analysis showed tight paired clustering of UF-EOs with matched T-EOs across three independent patients. Both organoid types demonstrated equivalent hormone responsiveness, with progesterone-induced secretory differentiation evidenced by glandular folding, subnuclear vacuolization, glycogen accumulation, and upregulation of SPP1, PAEP, and 17HSDβ2. IUA-derived UF-EOs displayed 190 differentially expressed genes, with enrichment of cell cycle, TGF-β, and Hippo signaling pathways. TGF-β2 and Smad2 were significantly upregulated and SOX9, PCNA, and Ki67 were downregulated, consistent with compromised regenerative capacity. HTR8/SVneo spheroids were successfully microinjected into organoid lumens, with luminal localization observed at 24 h.</p><p><strong>Conclusion: </strong>We have introduced uterine lavage fluid as a feasible source for generating endometrial organoids with equivalent fidelity to tissue-derived counterparts. UF-EOs provide a non-invasive alternative that enables organoid-based research in populations previously excluded from invasive sampling, including patients with intrauterine adhesions. Our findings demonstrate applications in disease mechanism investigation, endometrial receptivity assessment, and modeling of early embryo-epithelium interactions. Future studies employing larger cohorts and integrated multicellular systems will be essential to validate the clinical utility of this approach.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148449504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Splice-altering TP53 missense mutations as drivers of dysfunction and targets for RNA-based therapy.","authors":"Sun-Ku Chung, Han-Byul Jung, Su-Jin Baek, Sang-Min Park, Jinchul Kim, Seo-Young Lee, Byungkuk Min, Yong-Kook Kang","doi":"10.1186/s13287-026-05176-1","DOIUrl":"10.1186/s13287-026-05176-1","url":null,"abstract":"<p><p>TP53 missense mutations introduce single amino acid substitutions in the p53 protein, which can lead to diverse functional consequences. However, their post-transcriptional impact, particularly on RNA splicing, remains underexplored. Herein, we analyzed cancer genome databases and identified 34 TP53 missense and synonymous mutations capable of generating de novo-splice sites. Using minigene assays, we confirmed the splicing-altering potential of several mutations, including c.178 C > A, c.182 A > G, c.318 C > G, c.356 C > G, c.362 C > A, c.551 A > G, and c.922 C > G. To assess the physiological relevance of these splicing changes, we developed mutant TP53 knock-in cell models using bacterial artificial chromosome DNA-mediated homologous recombination. These missense mutations can function as frameshift or hypomorphic mutations due to aberrant splicing, significantly compromising TP53 mRNA integrity. Meanwhile, severe impairment of constitutive splicing suggests that it correlates with an increased likelihood of nonsense-mediated mRNA decay for mutation-driven alternative transcripts carrying a frameshifted premature stop codon. By designing antisense morpholino oligomers targeting de-novo splice site, we were able to restore csV1 expression and enhance p53 function. This reclassification of select p53 mutations from simple missense to splicing-disruptive mutations reveals their underlying loss-of-function mechanisms and highlights their therapeutic reversibility. Our findings present a novel framework for RNA-based therapeutic strategies aimed at correcting splicing defects in TP53-mutant cancers.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulatory efficacy of culture condition-dependent modulation of mesenchymal stem cells.","authors":"Qiuli Sun, Xi Zhang, Huixian Dong, Chunliu Mi, Shaolei Geng, Qin Li, Jihong Zhang, Xiaoyin Wang, Tianyun Wang","doi":"10.1186/s13287-026-05169-0","DOIUrl":"10.1186/s13287-026-05169-0","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs), due to their unique anti-inflammatory, immunosuppressive, immunomodulatory, and regenerative properties, have been used in the treatment of various diseases. Despite the advancements in the technological development of culture media and cell cultures, ensuring that MSCs have immune regulatory functions while maintaining their application remains challenging. In this review, factors that affect the proliferation, stemness, immune regulation, and paracrine properties of MSCs in culture are summarized, and divided into three groups: culture environment, cytokines, and chemical additives. Understanding the factors that affect the immune regulatory properties of MSCs in culture will contribute to the large-scale cultivation of MSCs, in order to obtain high-quality MSCs for disease treatment.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanofiber-reinforced ECM-based bioink for hybrid biofabrication of adventitia-mimetic anisotropic vascular constructs.","authors":"Zhiyuan She, Yingqian Zhou, Shan Mou","doi":"10.1186/s13287-026-05168-1","DOIUrl":"10.1186/s13287-026-05168-1","url":null,"abstract":"<p><strong>Background: </strong>Tissue-engineered blood vessels are essential for vascular grafting. Despite significant progress, current research predominantly focuses on the macroscopic scale of vascular grafts, neglecting the anisotropic microstructure of the vascular wall, particularly the adventitia, which plays a key role in the mechanical stability and functional performance of native vessels. Consequently, this aspect remains underexplored in current vascular tissue engineering strategies, limiting the full potential of vascular graft development.</p><p><strong>Methods: </strong>In this study, we developed a novel hybrid biofabrication strategy combining electrospinning and coaxial extrusion printing with nanofiber-reinforced bioinks to fabricate vascular constructs that mimic the anisotropic structure of the vessel wall. The bioink, composed of a gelatin methacryloyl hydrogel matrix, contains short electrospun polycaprolactone fibers and vascular-derived extracellular matrix, which improve the mechanical stability, printability, and biocompatibility of the bioink while also providing micro/nano-scale structure.</p><p><strong>Results: </strong>Using coaxial extrusion printing, we successfully fabricated vascular constructs with well-aligned fibers and cells oriented along the long axis of the artificial vessel, mimicking the micro-/nano-architecture of the adventitia. Finite element analysis revealed that shear stress during extrusion induced fiber and cell alignment, creating anisotropic structures that enhance the potential for vascular tissue engineering applications. In vivo studies demonstrated that these constructs promote host integration and vascular ingrowth without causing excessive inflammation.</p><p><strong>Conclusions: </strong>A promising strategy for fabricating vascular grafts with biomimetic adventitia-like structures is presented in this study, thereby providing a versatile platform for engineering vascular and other anisotropic tissues.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stem cells reverse ovarian dysfunction by inhibiting autophagy in polycystic ovary syndrome mice.","authors":"Qiwei Liu, Lei Zhan, Liang Kong, Yuanyuan Ma, Jinjuan Wang, Junhui Zhang","doi":"10.1186/s13287-026-05162-7","DOIUrl":"https://doi.org/10.1186/s13287-026-05162-7","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is a chronic inflammatory disorder that affects the reproductive health of 6%-20% of women of reproductive age worldwide. However, PCOS is yet to be completely cured. As a biomaterial that regulates the conditions of the female reproductive system, many studies have demonstrated that mesenchymal stromal cells (MSCs) have significant therapeutic potential for restoring impaired ovarian function. The purpose of the study was to examine the therapeutic benefits of human umbilical cord mesenchymal stromal cells (Huc-MSCs) in mice with dehydroepiandrosterone (DHEA)-induced PCOS and to assess their effects on ovulation, sex hormones, and the estrous cycle.</p><p><strong>Methods: </strong>Flow cytometry (FCM) was used to identify Huc-MSCs. The expression of the autophagy-related proteins LC3 II, Beclin1, and mammalian target of rapamycin (mTOR) was evaluated by Western blot (WB) and real-time quantitative polymerase chain reaction (RT-qPCR). Changes in the number of autophagosomes were assessed by transmission electron microscope (TEM). DHEA was subcutaneously injected into female C57BL/6J mice to develop a PCOS model. The morphological changes in the ovaries and the number of oocytes at various stages of development in PCOS mice were observed using hematoxylin and eosin (H&E) staining. The levels of sex hormones were measured using enzyme-linked immunosorbent assay (ELISA), and the estrous cycle of PCOS mice was monitored using vaginal smears.</p><p><strong>Results: </strong>The PCOS patient group exhibited significantly higher levels of ATG5 and Parkin than the control group and a significant increase in the number of autophagosomes in the GCs of PCOS patients compared with those of non-PCOS women. Huc-MSCs are capable of repairing the impaired estrous cycle in PCOS mice and decreasing the level of testosterone (T) and the ratio of luteinizing hormone (LH)/ follicle-stimulating hormone (FSH) (LH/FSH ratio). Huc-MSCs are also able to repair ovulatory functions and facilitate oocytes maturation in PCOS mice. Autophagy suppression can improve oocytes viability in mice. Huc-MSCs also can inhibit granulosa cell autophagy, promote oocytes development, maintain homeostatic hormone levels, and restore the estrous cycle in PCOS mice. Huc-MSCs have the potential to treat ovarian dysfunction in PCOS mice by inhibiting autophagy pathway. In KGN cells and in DHEA-induced PCOS mice, mTOR expression was significantly downregulated. Huc-MSCs treatment markedly upregulated mTOR levels.</p><p><strong>Conclusions: </strong>Our results suggest that Huc-MSCs improve ovarian dysfunction in PCOS by inhibiting autophagy, providing experimental evidence for the clinical application of hUC-MSCs and offering a new therapeutic approach for the treatment of PCOS.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}