Science of Advanced Materials
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2024
·Vol. 16
·期 11
·1150-1156
·
IF 0.9
Yang Shiqing,Lian Yunfei,Song Ge,Ni Huiyan,Jia Beidi,Qian Xinyu,He Guanxu,Ullah Aftab,Qi Xueyong
Background: The uterine endometrium plays a important role in the processes of fertilization and embryogenesis, with its impairment or dysfunction leading to pathologies such as intrauterine adhesions, miscarriage, and infertility. In addressing endometrial damage, the application
of stem cell has attracted considerable attention. To promote the paracrine capabilities of mesenchymal stem cells (MSCs), this study employed pro-inflammatory cytokines (Tumor Necrosis Factor-α and Interferon-γ, TNF-α and IFN-γ, IT) along with 3D culture techniques
on pretreated MSCs (3D-IT-MSCs). We focused on evaluating the therapeutic potential of 3D-IT-MSCs and elucidating the mechanisms involved in endometrial repair. Method: Pretreated MSCs were co-cultured with human umbilical vein endothelial cells (HUVECs) or drug-induced endometrial
stromal cells (ESCs) to observe the promoting effect on biological function. Results: The findings demonstrated that 3D-IT-MSCs exhibit markedly elevated paracrine molecule expression and secretion compared to conventional MSCs. Additionally, treatment with 3D-IT-MSCs significantly
promoted the proliferation and migration of HUVECs and ESCs, resulting in increased HUVECs angiogenesis and inhibition of mifepristone-induced ESCs apoptosis. Conclusion: Our findings demonstrated that the combined approach of applying pro-inflammatory cytokines and 3D culture techniques
on pretreated MSCs holds substantial promise as a therapeutic strategy for repairing endometrial injuries.
研究领域:
生殖生物学
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干细胞治疗
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组织工程
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再生医学
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Current Stem Cell Research & Therapy
·
2024
·Vol. 20
·期 7
·795-809
·
IF 2.1
Wenpo Feng,Chenxi Feng,Binbin Wang,Mengqi Lv,Xicong Li,Aihua Jing,Yuanhao Qiu,Huashan Gao,Gaofeng Liang
BackgroundWith the passage of time, the incidence rate of diabetes continues to rise. As a common and serious complication of diabetes, the economic burden of diabetes ulcers is also increasing. However, there is currently no unified clinical treatment strategy for its repair and research, and the treatment effect is not satisfactory. Exosomes derived from MSCs play a crucial role in improving diseases.MethodsThis study used the explant culture method to isolate human umbilical cord mesenchymal stem cells (hucMSCs) from Wharton’s jelly, which were identified by flow cytometry and differentiation potential and evaluated tumorigenic potential. The supernatant of P3-P5 cell culture medium was collected and high-concentration human umbilical cord mesenchymal stem cell exosomes (hucMSCs-Exos) were isolated through ultracentrifugation. Qualitatively identified were finished by transmission electron microscopy (TEM), nanosight tracking analysis (NTA) and Western blot (WB). CCK-8 assay and cell scratch experiment were used to evaluate the effects of hucMSCs-Exos on proliferation and migration ability of cells; chicken embryo chorioallantoic membrane experiment (CAM) was used to evaluate the angiogenic effect of hucMSCs-Exos. In order to study the effect of hucMSCs-Exos on diabetes wound healing, type 2 diabetes mellitus (T2DM) mouse model was constructed by a high-fat feeding and a low-dose streptozotocin (STZ) injection. Fasting blood glucose and blood lipids were measured and oral glucose tolerance test (OGTT) was conducted; HucMSCs-Exos were subcutaneously injected into the T2DM wound model mice which were established by a high-fat diet and by a low-dose STZ, and the wound healing was evaluations.ResultsCells were isolated by explant culture method, and flow cytometry analyses showed that these isolated cells were positive for cells markers CD29, CD90, and CD105, while negative for CD34 and CD45; moreover, these cells could be induced to osteoblasts, adipocytes, and islet-like cells. The tumorigenic experiments showed that these cells have no tumorigenicity. HucMSCs-Exos, separated by ultracentrifugation, displayed spherical or ellipsoidal vesicles with a diameter of around 120 nm, positive for CD9, CD63, and CD81. And they could promote cell proliferation and migration, as well as promote vascular growth (p < 0.01). In vivo experiments showed that hucMSCs-Exos had a promoting effect on wound repair in T2DM mice (p < 0.01).ConclusionThis study provides a new scheme for the treatment of T2DM ulcer.
研究领域:
再生医学
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糖尿病研究
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干细胞治疗
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分子生物学
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伤口修复
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Nano Select
·
2024
·
IF 0
Leihao Lu,Xiao Yang,Dulin Wang,Suting Zhong,Ying Zhang,Guanshan Zhou,Chenlin Li,Jie Wang,Mingying Yang
Scaffold and stem cells are the key elements in the procedure of bone repair. Bombyx mori silk fibroin (SF) is the proper material for bone tissue engineering due to its biocompatibility and its easy to obtain nanofiber structure. The suitable cell substrate is also an important factor because different cells have different adaptations to composite. For this case, selecting a scaffold that can promote osteogenic differentiation of various cells is crucial and meaningful. In this work, hydroxyapatite (HA) was deposited precisely onto each silk nanofiber by electrochemical mineralization (EC) to form SF/HA. SF/HA can promote the proliferation and osteogenic differentiation of both human bone marrow mesenchymal-derived stem cells (hMSCs) and human adipose-derived mesenchymal stem cells (hAMSCs). It also promot the expression of alkaline phosphatase (ALP) and osteogenic differentiation related genes. Western blot analyses show mitogen-activated protein kinase (MAPK) signal pathway is regulated by SF/HA. Therefore, the study provides a proper method to obtain a good composite SF/HA and it promotes the osteogenic differentiation of both hMSCs and hAMSCs.
研究领域:
生物材料
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组织工程
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干细胞分化
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生物医学工程
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DOI
Signal Transduction and Targeted Therapy
·
2026
·Vol. 11
·期 1
·341
·
IF 81.2
Liu Shuai,Ma Yunfeng,Zeng Yujie,Lv Dekang,Hou Zhijie,Huang Junxiu,Gong Yaqi,Feng Ruijun,Wang Zihan,Sui Ran,Huang Dan,Wu Yameng,Chen Nuo,Yao Mingzhi,Shan Ying,Huang Yuan,Wang Yuesheng,Yan Jinsong,Peng Fei,Liu Quentin,Xu Jie
Activation of quiescent or extremely slow-cycling breast cancer stem-like cells (qsBCSCs) contributes to tumor progression, yet the regulatory mechanisms involved in triple-negative breast cancer (TNBC) remain elusive. We developed a dual-reporter system combining NANOG-EGFP and H2B-mCherry pulse-chase labeling to separately identify qsBCSCs and active BCSCs (aBCSCs) in vitro and in vivo. aBCSCs display significant enrichment of glycolysis and lactylation signatures, a finding corroborated by single-cell RNA sequencing (scRNA-seq) of TNBC patient samples. Glycolytic enzyme Enolase 1 (ENO1) expression is positively correlated with elevated histone H4 lysine 12 lactylation (H4K12la) in aBCSCs. Functional studies revealed a positive feedback circuit in which ENO1-increased lactate promotes H4K12la, which in turn activates ENO1 transcription. The ENO1-lactate-H4K12la axis enhances proliferating cell nuclear antigen ( PCNA ) transcription to activate qsBCSCs. Suppression of ENO1 or H4K12la prevents PCNA upregulation and qsBCSC activation. Importantly, PCNA knockdown alone blocks the activation of qsBCSCs induced by exogenous sodium L-lactate (NALA). In orthotopic breast cancer mouse models, both genetic depletion of ENO1 and pharmacological inhibition of lactate production attenuated tumor growth by blocking qsBCSC activation. Clinically, ENO1 expression was strongly correlated with PCNA expression, with high expression predicting poor OS, RFS, and DMFS. Our results establish the ENO1-H4K12la-PCNA axis as a key metabolic‒epigenetic driver of qsBCSC activation and a therapeutic target in TNBC.
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International Journal of Oral Science
·
2026
·Vol. 18
·期 1
·52
·
IF 17.6
Di Tiankai,Liu Yuhan,Li Zhili,Wang Lulu,Li Peiyi,Nian Meng,Zhou Dezhong,Niu Lina,Chen Yujiang
The age-related decline in the pro-angiogenic capacity of mature dental pulp stem cells (DPSCs) severely limits pulp regeneration. We identify impaired glycolytic metabolism, driven by reduced glucose transporter type 1 (GLUT1) and hexokinase 2 (HK2) expression, as the key mechanism, as its inhibition diminished endothelial tube formation. To reverse this, we developed an aminolyzed highly branched poly(β-amino ester) (HBPA) as a vector for GLUT1/HK2 mRNA co-delivery, achieving >90% transfection efficiency with excellent biocompatibility. In vitro, conditioned medium from reprogrammed mature DPSCs resulted in a 2.0-fold increase in capillary length and a 2.3-fold increase in branch points, restoring angiogenic potential to levels equivalent to those of immature DPSCs. This efficacy translated robustly in vivo, where a tooth root slice model showed reprogrammed cells generated tissue with a vessel density of 10.2 vessels per mm 2 , 2.5-fold higher than that of untreated controls. Crucially, this level of vascularization was statistically indistinguishable from that achieved by the benchmark immature DPSCs. Our study demonstrates that HBPA-mediated metabolic reprogramming effectively rejuvenates mature DPSCs by restoring the “Metabolic-ECM-Angiogenesis Axis”, offering a translatable strategy for predictable, vascularized pulp regeneration.
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PubMed
高影响因子
FASEB JOURNAL
·
2026
·Vol. 40
·期 13
·e72115
·
IF 4.3
Hanjing Song,Jiani Zhang,Suman Huo,Xian Xu,Caiyan Huang,Lin Chen,Xueqin Yang,Yeqing Qian,Xiao-Jing Zhu
The transcription factor p63 is indispensable for epithelial stem cell proliferation/differentiation and epidermal development, with alterations in the p63 pathway underlying a subset of ectodermal dysplasias. Despite its critical role, the mechanisms regulating p63 expression remain poorly understood. Here, we identify an m 6 A-mediated posttranscriptional mechanism controlling the expression of ΔNp63 , the predominant functional p63 isoform in epidermal basal cells. We found that Cre-mediated conditional deletion of Mettl16 , encoding a conserved m 6 A methyltransferase, in mouse epithelial basal cells caused severe skin developmental abnormalities, reminiscent of human ectodermal dysplasias. RNA sequencing revealed significant downregulation of ΔNp63 and its target genes in Mettl16- deficient skin, which linked METTL16 to p63 pathways. Mechanistically, we demonstrated that METTL16 directly binds to ΔNp63 mRNA to mediate its m 6 A modification; this modified ΔNp63 mRNA is subsequently recognized by the m 6 A reader IGF2BP2, which stabilizes ΔNp63 mRNA and thereby modulates its protein levels. Critically, restoration of ΔNp63 expression mitigated the epidermal defects in Mettl16 -deficient mice. Collectively, our findings uncover a novel METTL16-m 6 A-IGF2BP2- ΔNp63 regulatory axis governing epidermal development, providing insights into the etiology of ectodermal dysplasias. Graphical p63 is essential for epithelial stem cell proliferation, differentiation, and epidermal development, and alterations in its pathway are associated with human ectodermal dysplasias. This study identifies a posttranscriptional mechanism whereby METTL16 directly binds to p63 mRNA and adds m6A modifications. The m6A reader IGF2BP2 recognizes these modifications, stabilizes p63 mRNA, and controls p63 protein levels. Together, these findings uncover a METTL16-m6A-IGF2BP2-p63 regulatory axis governing epidermal development, offering new insights into the etiology of human ectodermal dysplasias.
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ACS Applied Polymer Materials
·
2026
·
IF 5.2
Shaokun Zhang,Bo Zou,Yiwei Zhang,Zhenhao Teng,Qingqing Sun,Jianzhong Xu,Xiaomeng Li
Microspheres have been widely applied in osteoarthritis (OA) treatment and tissue engineering because of their favorable biocompatibility and drug delivery capabilities. However, single-component microspheres often fail to provide satisfactory therapeutic outcomes under the complex mechanical environment of the joint, particularly under persistent friction and shear stress. In this study, poly(l-lactic acid) (PLLA)–gelatin grafted with hydroxyphenyl propionic acid (GelHPA) core–shell microspheres were successfully fabricated via an in situ enzymatic cross-linking method. The PLLA core provides structural support and serves as a reservoir for bioactive agents, such as kartogenin (KGN) and nanohydroxyapatite (nHA), while the GelHPA shell offers a hydrated, gelatin-derived interface with improved cytocompatibility and lubrication-related properties. The GelHPA shell supported cell adhesion and spreading on the microsphere surface, while KGN- and nHA-loaded microspheres promoted chondrogenic and osteogenic differentiation of mesenchymal stem cells, respectively. Overall, the PLLA-GelHPA core–shell microsphere system integrates mechanical support with biological functionality, offering a promising injectable platform for OA-related osteochondral repair and tissue engineering applications.
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Stem Cell Reports
·
2026
·Vol. 21
·期 9
·
IF 5.6
Li Wenjing,Feng Yiting,Han Dongbo,Ao Yanxiao,Michael W. Chen,Li Ning,Jin Yuhong,Liang Haiwei,Liu Wen,Zhu Xiaoyu,Du Yanan
Understanding the regulation of hematopoietic stem and progenitor cell (HSPC) fate and translating it into effective culture strategies remains a significant challenge. Asymmetric lysosomal inheritance during HSPC division has been shown to predict variations in daughter cell activity and fate, yet the underlying regulators remain unclear. Through cell-cell communication analysis of bone marrow single-cell sequencing data, we identified the Notch ligand Delta-like protein 1 (DLL1) as a potential regulator in HSPC asymmetric division (ACD). Interactions between DLL1-presenting microparticles (MP-Ds) and HSPCs were observed in addressable microwell arrays, simulating cellular responses to localized niche signals. Long-term single-cell tracking revealed that MP-D interactions polarized HSPC lysosomes toward the contact site, directing division orientation and consequent asymmetric lysosomal inheritance in paired daughter cells. Furthermore, this co-culture system enhanced long-term hematopoietic reconstitution capacity of HSPCs in serial transplantations. Our findings support an association between HSPC ACD and the presentation mode of DLL1 signals, which enhances the ex vivo maintenance of HSPCs.
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Frontiers in Immunology
·
2026
·
IF 7
Gaohua Li,Lingping Zhao,Jingzhi Shen,Haiyang Wang,Jinru He,Yiming Liu,Ruge Zang,Tiantian Cui,Quan Zeng,Junnian Zhou,Wen Yue,Yanan Wang,Jiafei Xi
BackgroundCarcinoembryonic antigen (CEA) is overexpressed in most colorectal cancers (CRC) and serves as a promising immunotherapeutic target. However, current immune cell therapies against CRC show limited clinical efficacy, and the lack of renewable, standardized cell sources hampers broader application. The present study aimed to establish a scalable source of CEA-targeted natural killer (NK) cells from engineered human embryonic stem cells (hESCs).MethodshESCs were genetically engineered to express a CEA‑specific chimeric antigen receptor (CAR). The modified hESCs were subsequently differentiated into NK cells, yielding a homogeneous population of CAR hESC-NK cells. In vitro cytotoxicity against CEA-high CRC cell lines was evaluated using LDH and IFN-γ release assays. For in vivo assessment, we established a xenograft mouse model bearing CEA-positive CRC tumors. Following adoptive transfer of CAR-hESC-NK cells, tumor growth was monitored by bioluminescence imaging, overall survival was recorded for Kaplan–Meier analysis, and the persistence of transferred cells in peripheral blood was examined by flow cytometric analysis at serial time points.ResultsIn vitro, CAR hESC‑NK cells demonstrated potent and specific cytotoxicity against CEA-high CRC cell lines, along with significantly enhanced cytokine secretion compared to unmodified NK cells. In the xenograft model, adoptive transfer of CAR hESC‑NK cells resulted in marked tumor growth inhibition and prolonged survival, with no observable off‑target toxicity. Importantly, the CAR CEA‑ESC line maintained stable transgene expression and could serve as a renewable seed cell source.ConclusionWe have established a scalable platform for producing CEA‑targeted NK cells from engineered hESCs, providing an off‑the‑shelf, homogeneous cell product with robust antitumor activity. This strategy provides effective and specific immunotherapy against CEA-positive colorectal cancer and holds potential for other CEA-expressing malignancies.
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CHEMISTRY OF MATERIALS
·
2026
·
IF 7.1
Qian Yang,Zhuoying Chen,Ziyao Mao,Guangzhao Li,Lijing Hao,Yunhua Chen
Mesenchymal stem cells (MSCs) have attracted considerable interest for therapeutic delivery owing to their multilineage differentiation capacity, low immunogenicity, and broad immunomodulatory functions. However, the development of biomaterials that simultaneously enable efficient stem cell encapsulation, minimally invasive delivery, and improved retention remains a significant challenge. Herein, we report a supramolecular granular hydrogel matrix with an intrinsic macroporous architecture designed to enhance the MSC viability and in vivo retention. The resulting granular hydrogel exhibits robust self-healing and dynamic mechanical properties arising from reversible physical interactions and can be readily processed as a three-dimensional (3D) printable ink for continuous and stable extrusion. This granular hydrogel supports long-term 3D culture of MSCs and markedly enhances cell adhesion and stemness maintenance compared with conventional two-dimensional culture conditions. In a murine cell delivery model, MSC-laden GMU granular hydrogels maintained a stable 3D matrix following injection, leading to significantly improved cell retention in vivo. These results demonstrate that the GMU granular hydrogel is a promising carrier platform for stem cell delivery and regenerative therapy.
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JOURNAL OF BIOMATERIALS APPLICATIONS
·
2026
·
IF 2.4
Jia Wu,Renguo Gong,Yongmei Wen,Shan Kong,Pan Yang,Xia Deng
Bone and cartilage regeneration remains a major clinical challenge due to the limited intrinsic repair capacity of musculoskeletal tissues. Biomaterial strategies capable of regulating stem cell behavior at the single-cell level offer new opportunities for precise control of tissue regeneration. Herein, we developed tannic acid–metal (TA–metal) coordination systems incorporating Fe3+, Sr2+, and Mg2+ ions as single-cell nano-coatings to modulate the pericellular microenvironment of bone marrow–derived mesenchymal stem cells (BMSCs). The physicochemical properties of the TA–metal coatings, including protein adsorption, surface morphology, surface charge, ion release behavior, and elemental composition, were systematically characterized. All TA–metal systems formed conformal coatings on individual cells with excellent cytocompatibility and showed detectable retention during early culture. The TA–metal nano-coatings significantly regulated cell morphology and cytoskeletal organization in a metal ion–dependent manner. Notably, TA–Sr and TA–Mg coatings promoted enhanced cell spreading and well-organized actin structures. Tri-lineage differentiation assays revealed distinct lineage-specific regulatory effects. TA–Fe nano-coatings preferentially enhanced adipogenic differentiation, whereas TA–Sr coatings significantly promoted chondrogenic matrix production while supporting osteogenic differentiation. TA–Mg nano-coatings exhibited the strongest osteogenic potential, as evidenced by increased alkaline phosphatase activity and extracellular matrix mineralization. Collectively, these results demonstrate that TA–metal single-cell nano-coatings enable programmable, ion-specific regulation of stem cell fate within an identical coordination framework. This cell-level biomaterial strategy provides a versatile platform for skeletal tissue engineering and cell-based regenerative therapies.
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Yonghu Chen,Linying Hu,Qiang Fu,Hongzhen Chen,Zhe Jiang,Xuezheng Li
Ethnopharmacological relevance Pulmonary fibrosis (PF) is a progressive interstitial lung disease characterized by alveolar epithelial injury, inflammation, and excessive extracellular matrix deposition, yet current therapeutic options remain limited. Panax ginseng C.A. Meyer, a renowned qi-tonifying herb in traditional Chinese medicine, has long been used to enhance spleen and lung function by replenishing qi. However, the mechanism of action of its primary active component, ginseng stem and leaf saponins (GSLS), in pulmonary fibrosis remains incompletely understood. Aim of the study : This study aims to elucidate the protective role of GSLS against pulmonary fibrosis by investigating how GSLS regulates mitochondrial transcription factor A (TFAM)–mtDNA homeostasis and suppresses PANoptosis in alveolar epithelial cells. Materials and methods The major constituents of GSLS were identified using UHPLC–Q Exactive HFX. A BLM-induced mouse model of pulmonary fibrosis and an MLE-12–primary fibroblast co-culture system were established to evaluate the therapeutic effects of GSLS. Surface plasmon resonance (SPR) and cell thermal shift assays (CETSA) were performed to assess the direct interaction and thermal stability between GSLS and TFAM. Co-immunoprecipitation (Co-IP), RT-qPCR, and immunofluorescence were used to evaluate PANoptosome assembly, cytosolic double-stranded DNA (dsDNA) leakage, and fibrotic marker expression. Results GSLS was found to contain multiple active ginsenosides, including Rk2, CK, Rk3, and Rf. In vivo , GSLS markedly alleviated BLM-induced lung pathological injury, reduced collagen deposition, and decreased oxidative stress. In vitro , GSLS directly bound to TFAM and enhanced its thermal stability. RT-qPCR and immunofluorescence analyses further demonstrated that GSLS effectively suppressed abnormal cytosolic dsDNA leakage, reduced MLE-12 cell death, and ameliorated mitochondrial dysfunction. Moreover, GSLS inhibited the assembly of the PANoptosome complex, suppressed epithelial PANoptosis, and decreased the expression of fibrosis-related proteins. Conclusion GSLS mitigates BLM-induced pulmonary fibrosis by stabilizing TFAM, maintaining mtDNA homeostasis, and suppressing PANoptosis. This clarifies the potential mechanism of GSLS therapy for PF.
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