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Materials Today Bio · 2025 · IF 10.2

In Situ Vascularization and Epithelialization of Segmental Bioengineered Trachea Based on Marrow-Derived Stem/Progenitor Cells

Fei Sun,Yibo Shan,Shu Pan,Yi Lu,Zhiming Shen,Jianwei Zhu,Lei Yuan,Qi Wang,Wenxuan Chen,Hao Chen,Hongcan Shi

The success of tracheal transplantation depends on the rapid establishment of vascularization and epithelialization to support functional tissue formation. This study presents an innovative approach for in situ transplantation of a biomimetic tracheal graft, integrating microvascularization and epithelialization. First, endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) were isolated and purified from bone marrow, serving as seed cells for graft vascularization and epithelialization. Next, 3D printing was employed to create a bilayered tracheal graft using poly(ε-caprolactone) (PCL) and decellularized tracheal extracellular matrix (dtECM), which provided both optimal biomechanical properties and angiogenic potential. MSCs and EPCs were seeded on the inner and outer surfaces of the graft, respectively, and implanted in a long-segment in situ transplantation model. Six months post-transplantation, CT scans revealed a patent luminal space, bronchoscopy confirmed successful anastomosis, scanning electron microscopy showed abundant cilia on the inner graft surface, and α-SMA immunofluorescence demonstrated significant neovascularization. The PCL/dtECM graft exhibited excellent biomechanical properties, along with enhanced cell adhesion and proliferation. The combination of EPCs and MSCs effectively promoted both vascularization and epithelialization, ensuring successful graft integration and long-term survival of the experimental animals.

CAS / MDL: 7719-12-2
✓ 已验证 产品关联 DOI PubMed 高影响因子
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PLoS Genetics · 2025 ·Vol. 21 ·期 5 ·e1011704 · IF 3.7

Age-associated decline of Coenzyme A leads to intestinal stem cells dysfunction via disturbing iron homeostasis

Zhiming Liu,Gang Du,Yi Chen,Haiyang Chen

The decline in adult stem cell performance is closely linked to tissue malfunction and the rising incidence of age-related diseases. To investigate the molecular basis of these impairments, our screening strategy identified reduced activity in the pantothenate/coenzyme A (CoA) pathway within aged ISCs. Furthermore, exogenous CoA supplementation restructured ISC metabolic pathways, reversing age-induced hyperproliferation and intestinal dysfunction, and thus extending Drosophila lifespan by curbing excessive iron accumulation in ISCs. These findings uncover a new mechanism of stem cell aging and propose that pantothenate and CoA could be potential therapeutic targets for treating age-related diseases and enhancing healthy aging in humans. In our study, we explored the connection between the aging of adult stem cells and the rise of age-related diseases, uncovering a significant metabolic link. As stem cells age, a key metabolic pathway involving pantothenate and CoA becomes less active, leading to an accumulation of excess iron, which disrupts cellular function and contributes to the aging process. To counteract this decline, we added pantothenate and CoA to the aging stem cells, restoring their normal function, reducing iron buildup, and ultimately improving the health and lifespan of old fruit flies. This simple intervention not only highlights the potential of pantothenate and CoA as powerful tools to combat the effects of aging but also suggests broader implications for treating age-related diseases and promoting healthy aging in humans. Our findings provide a new perspective on the biology of aging and open up exciting new avenues for therapeutic interventions that could improve the quality of life for older individuals.

研究领域: 细胞生物学 · 分子生物学 · 衰老研究 · 营养学
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Journal of Materials Chemistry B · 2025 · IF 5.7

Metal-Phenolic Network Coatings Delivering Stem Cells from Apical Papilla Derived Nanovesicles for Bone Defect Regeneration

Jiuzhi Ma,Qi Feng,Zhipeng Sun,Manru Wang,Qiyuan Dai,Yue Huang,Xiaodong Cao,Qingtao Li

Bone defects have a broad impact, with over four million patients globally needing bone defect reconstruction every year due to various causes. Extracellular vesicle-functionalized scaffolds have recently emerged as a novel therapeutic approach for enhancing bone tissue regeneration. However, the clinical application of exosomes is limited by their low yield and rapid in vivo clearance. To address these challenges, we prepared nanovesicles (SCAPs-NVs) from stem cells of the apical papilla (SCAPs) using the extrusion method and loaded them into a tannic acid-Fe3+ network modified decellularized diaphragmatic tendon matrix. SCAPs can be abundantly obtained directly from extracted immature permanent teeth, are more readily available than other stem cells and also have the potential for multi-lineage differentiation. The strong interaction between tannic acid (TA) and the phospholipid bilayer of SCAPs-NVs enabled the controlled release of SCAPs-NVs. In our study, under the same conditions, the yield of SCAPs-NVs was approximately 23-fold higher than that of exosomes obtained by ultracentrifugation, highlighting the efficiency of the extrusion method. Moreover, MicroRNA sequencing of SCAPs-NVs reveals that they are enriched in angiogenic and osteogenic miRNAs. In vitro results showed that the composite scaffold loaded with SCAPs-NVs stimulated osteogenic differentiation of mesenchymal stem cells and promoted angiogenic activity of human umbilical vein endothelial cells. Micro-CT and histological evaluation confirmed the efficacy of the NVs-functionalized scaffold in promoting bone regeneration within a rat cranial defect model. This study provides novel insights into the therapeutic potential of nanovesicles, particularly SCAPs-NV, for clinical translation in bone regeneration.

研究领域: 生物材料学 · 再生医学 · 组织工程学
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Materials Today Bio · 2025 · IF 10.2

Transformable self-assembling peptide nanoplatforms with tumor microenvironment responsiveness for tumor stem cell suppression and immunomodulation

Chen Wei,Xinyu Sun,Lijuan Gao,Yue Wang,Fantao Lin,Yao Du,Xiaoyu Zhao,Wei Gao,Jingkun Bai

Breast cancer stem cells (BCSCs) drive tumor formation and growth via self-renewal, differentiation, and high tumorigenic potential, and the persistence of BCSCs is an important cause of treatment failure in patients with breast cancer. In addition, the tumor microenvironment promotes the maintenance of BCSC stemness, inhibits immune cell activity, and forms an immune escape “barrier”. In this study, we developed an amphiphilic peptide nanocarrier system, PA/Pep1, with an RGD-targeting sequence. The delivery system simultaneously encapsulates the hydrophobic drugs paclitaxel (PTX) and all-trans retinoic acid (ATRA) and releases them in response to low pH in the tumor microenvironment. PA/Pep1 causes apoptosis in breast cancer cells, induces the differentiation of BCSCs and inhibits their expression, thus enhancing the killing effect of PTX. In breast cancer, PA/Pep1 effectively alleviates immune evasion by modulating transforming growth factor-β (TGF-β) and interleukin-6 (IL-6), thereby reducing the expression of programmed cell death-ligand 1 (PD-L1). Importantly, the transformation of the nanosystems into forms with high aspect ratios under acidic conditions effectively reduced drug efflux and extended the duration of drug action. In conclusion, the combination of stem cell therapy and immunotherapy, as well as the development of novel deformable amphiphilic peptide nanocarrier systems, provides new possibilities for breast cancer treatment.

CAS / MDL: 38215-36-0
研究领域: 生物医学 · 肿瘤学 · 免疫学 · 药剂学
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Nature Communications · 2025 ·Vol. 16 ·期 1 ·1-20 · IF 15.7

Vesicle-associated membrane protein 5 is an intrinsic defense factor for embryonic stem cells against coronaviruses

Dong Huijun,Pan Zihang,Jiao Pengtao,Ye Fei,Peng Qi,Yu Yanying,Lai Xinyuan,Li Huan,Guan Zhao,Deng Juan,Shen Tao,Tan Wenjie,Shi Yi,Ding Qiang,Luo Jianyuan,Li Tong,Zhuang Hui,Xiang Kuanhui

Embryonic stem cells (ESCs) display a distinctive resistance against various viruses, irrespective of any interferon response. Nevertheless, the underlying mechanism of this resistance remains unclear. In this study, we identify vesicle-associated membrane protein 5 (VAMP5) as a potent cell-autonomous defense factor against coronaviruses, including SARS-CoV-2, with high expression levels observed in ESCs and mesoderm. VAMP5 not only exhibits functional conservation in restricting the replication of SARS-CoV-2 and its variants, as well as other highly pathogenic coronaviruses, but also shows efficacy in combating the replication of viruses from other families. Mechanistic investigations reveal that VAMP5 localizes to double membrane vesicles (DMVs) and impedes viral replication by relying on its vesicle-side C-terminal domain to interact with the viral non-structural protein 8 (NSP8), thus inhibiting the synthesis of negative-strand RNA. Our research demonstrates that VAMP5 in ESCs disrupts the protected environment of DMVs, which is essential for viral genome replication, and interacts with RNA replication complexes to defend against viral infection. This provides a novel strategy for developing broad-spectrum antiviral treatments.

CAS / MDL: 1809249-37-3
研究领域: 细胞生物学 · 病毒学 · 分子生物学 · 发育生物学
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ACS Nano · 2025 · IF 16

The Key to Spinal Cord Recovery: Harnessing p21 Inhibition to Boost Neural Stem/Progenitor Cell Proliferation

Tiandi Xiong,Xiaofang Xiao,Haitao Zhao,Wen Yang,Xu Gao,Keni Yang,Kexin Zheng,Yuxuan Ji,Duoduo Xu,Ruoyao Fu,Longwei Li,Lulu Zhang,Yan Zhuang,Yanyan Chen,Jianwu Dai

Spinal cord injury (SCI) is a devastating traumatic condition of the central nervous system (CNS), usually resulting in irreversible motor and sensory deficits that severely compromise patients’ quality of life. Harnessing the untapped potential of endogenous neural stem/progenitor cells (NSPCs) may yield revolutionary therapeutic techniques for overcoming the limited NSPC proliferative capacity following SCI in adults. Single-cell sequencing results demonstrated that the limited proliferative capacity of NSPCs after SCI is associated with the upregulation of the p21. Herein, we developed a cationic liposome-based delivery system encapsulating p21 small interfering RNA (P21siRNA@LP) to enhance NSPC proliferation following SCI. P21siRNA@LP significantly increased the primary NSPC proliferation rate (145.4% on day 1 and 144.7% on day 3, respectively) while maintaining differentiation capacity in vitro. Transcriptomic and functional characterization showed that P21siRNA@LP modulated the expression of cyclin-dependent kinases in NSPCs, enhancing cell cycle pathways (enrichment score: 0.6691) and proliferation, with extracellular matrix reorganization (col1a1, col5a1) and gliogenesis (olig1/2) identified as key regulation pathways. Gelatin hydrogels incorporating P21siRNA@LP promoted dense tissue cable formation in T9 SCI rats, facilitating NSPC migration and proliferation at lesion sites, which accelerated locomotor function recovery. These findings emphasize cell cycle manipulation as a promising method to spinal cord regeneration, providing a basis for future therapeutic advances in CNS disorders.

研究领域: 神经生物学 · 再生医学 · 分子生物学 · 生物材料学 · 转化医学
✓ 已验证 DOI PubMed 高影响因子
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Materials Today Advances · 2025 · IF 8

A pH-triggered antioxidative stem cell spheroid platform restores paracrine signaling to enhance osteoporotic bone regeneration

Lina Huang,Chao Lin,Hanyi Hua,Zehao Chen,Yong Xu,Kezhen Zhou,Xiaoming Liu,Yifan Li,Jiangming Yu,Xiaojian Ye,Xiaoxiao Li,Shuai Jiang

In osteoporotic bone defects, bone marrow mesenchymal stem cells (BMSCs) play a pivotal role in tissue regeneration by orchestrating the local microenvironment through both differentiation and paracrine signaling. However, persistent pathological stimuli such as oxidative stress significantly impair their functionality, while limited cell survival and homing efficiency at the defect site remain major obstacles hindering therapeutic efficacy. To overcome these issues, we designed a stem cell delivery system using microfluidic techniques, in which microspheres were modified with resveratrol. This system leveraged a sustained-release liposomal formulation of resveratrol to enhance the antioxidant resilience of BMSCs. Simultaneously, the platform created a three-dimensional porous microenvironment using pH-responsive microspheres, which supported the maintenance of paracrine activity and promoted osteogenic differentiation of transplanted cells, thereby accelerating bone regeneration. In vitro experiments demonstrated that this system significantly enhanced mineralized nodule formation, accompanied by marked upregulation of osteogenesis-related genes and proteins including RUNX2, COL-1, and SP7. Furthermore, BMSCs exhibited increased secretion of key paracrine factors such as VEGFA, thereby improving proangiogenic support to endothelial cells. In vivo study, we employed an osteoporotic rat model with femoral bone defects, micro-CT imaging and multimodal histological analyses confirmed that the proposed platform markedly facilitated new bone formation and structural tissue reconstruction. Collectively, this study proposes a synergistic strategy for osteoporotic bone repair, providing a new approach to cell therapy design.

研究领域: 再生医学 · 组织工程 · 干细胞生物学 · 骨科学 · 生物材料学 · 药物递送系统
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

Injectable Thermosensitive Hydrogel Encapsulating Mesenchymal Stem Cell Membrane-Based Biomimetic Liposomes for Local Rheumatoid Arthritis Treatment

Lan Ma,Taoming Dong,Liang Pei,Xinchi Jiang,Jianqing Gao

In rheumatoid arthritis (RA), the immune system mistakenly attacks joints by releasing harmful inflammatory substances that cause swelling and gradual joint damage. As inflammation progresses, patients experience severe pain and reduced mobility. Therefore, localized anti-inflammatory and analgesic therapeutic interventions may offer a viable strategy for the clinical management of RA. To effectively regulate joint inflammation, it is essential to prolong the retention time of therapeutic agents within the joint cavity and enhance the target delivery capability. To achieve this, we loaded mesenchymal stem cell membrane biomimetic liposomes (MSCsome) into the injectable thermosensitive hydrogel for RA therapy in this study. Specifically, the thermosensitive hydrogels injected into the joint cavity enabled the sustained and localized release of dexamethasone (Dex)-encapsulated MSCsome due to the slow degradation rate, and subsequently, Dex-MSCsome can be internalized by activated macrophages due to the intrinsic targeting capability. This composite biomimetic formulation effectively alleviated joint inflammation and pain, while significantly promoting articular cartilage repair. In conclusion, this study presents a novel strategy using cell membrane-based biomimetic carriers combined with thermosensitive hydrogels, offering a promising platform for targeted and sustained anti-inflammatory therapy.

CAS / MDL: 8002-43-5
研究领域: 免疫学 · 药剂学 · 生物材料 · 炎症性疾病 · 转化医学 · 分子治疗 · 再生医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Cell and Developmental Biology · 2025 · IF 4.3

Psoralen-mediated regulation of osteogenic differentiation of periodontal ligament stem cells: involvement of the mTOR pathway

Yujia Wang,Hongbo Zhang,Jie Yu,Jin Jing,Zhaojiang Fu,Yuanping Hao,Qihang Huang,Ruibin Ma,Yingjie Xu,Yingtao Wu

Background Chronic periodontitis is a prevalent inflammatory and destructive oral disease, and its primary treatment is to control the development of inflammation and promote the regeneration of periodontal tissue. Psoralen (Pso) has been shown to promote the osteogenic differentiation of periodontal ligament stem cells (PDLSCs), suggesting its potential as a therapeutic agent for osteogenic regeneration. Methods Network pharmacology and transcriptomic sequencing were exploited to screen target genes of Pso in PDLSCs, lentiviruses were employed to interfere with the target gene, and RT-qPCR was conducted to assess the expression levels of osteogenesis-related factors. Pso-loaded mesoporous polydopamine (MPDA-Pso) nanoparticles were constructed and evaluated in vitro , and in vivo osteogenesis was assessed in rats with alveolar bone defects. Results Network pharmacology analysis revealed that the mammalian target of rapamycin (mTOR) was a potential target of Pso, and Pso significantly modulated the expression levels of mTOR in PDLSCs and markedly enhanced osteogenic differentiation. However, Pso did not significantly alter osteogenesis-related genes in PDLSCs after mTOR-inhibitor treatment. We also confirmed that MPDA-Pso nanoparticles promoted the expression of osteogenesis-related genes in PDLSCs; and compared with the control group, observed that the mass of new bone was augmented in the MPDA-Pso group. Conclusion Pso was shown to promote the osteogenic differentiation of PDLSCs, and we postulate that this differentiation was facilitated in the LPS-induced inflammatory microenvironment via inhibition of the autophagy-related mTOR-signaling pathway. Additionally, the MPDA-Pso nanoparticles we developed promoted osteogenesis.

CAS / MDL: 62-31-7
研究领域: 干细胞生物学 · 牙周病学 · 药理学 · 再生医学 · 信号转导 · 纳米技术
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Bioactive Materials · 2025 · IF 20.3

Engineering a stem cell-embedded bilayer hydrogel with biomimetic collagen mineralization for tendon-bone interface healing

Tingyun Lei,Tao Zhang,Tianshun Fang,Jie Han,Chunyi Gu,Youguo Liao,Yang Fei,Junchao Luo,Huanhuan Liu,Yan Wu,Weiliang Shen,Xiao Chen,Zi Yin,Junjuan Wang

The tendon-bone interface effectively transfers mechanical stress for movement, yet its regeneration presents significant clinical challenges due to its hierarchical structure and composition. Biomimetic strategies that replicate the distinctive characteristics have demonstrated potential for enhancing the healing process. However, there remains a challenge in developing a composite that replicates the nanostructure of the tendon-bone interface and embeds living cells. Here, we engineered a nanoscale biomimetic bilayer hydrogel embedded with tendon stem cells for tendon-bone interface healing. Specifically, the biomimetic hydrogel incorporates intra- and extrafibrillar mineralized collagen fibrils as well as non-mineralized collagen fibrils resembling the tendon-bone interface at the nanoscale. Furthermore, biomimetic mineralization with the presence of cells realizes living tendon-bone-like tissue constructs. In the in vivo patella-patellar tendon-interface injury model, the tendon stem cell-laden biomimetic hydrogel promoted tendon-bone interface regeneration, demonstrated by increased fibrocartilage formation, improved motor function, and enhanced biomechanical outcomes. This study highlights the potential of the stem cell-laden biomimetic hydrogel as an effective strategy for tendon-bone interface regeneration, offering a novel approach to engineering complex tissue interfaces.

CAS / MDL: 154071-48-4
研究领域: 生物材料学 · 再生医学 · 组织工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ADVANCED MATERIALS · 2025 · IF 26.8

Neuroimmune Microenvironment Reprogramming via Immuno-piezoelectric Transducers for Synergistic Stem Cell Therapy in Traumatic Brain Injury

Linlin Liang,Xin Li,Kai Hu,Pingqiang Cai,Jianwu Wang,Jing Yu,Shasha Wang,Yuwei Zhao,Changgeng Xu,Siwei Li,Hong Liu,Changyong Wang,Jin Zhou

Secondary traumatic brain injury (TBI) induces a pro-inflammatory microenvironment that hampers neural stem cells (NSCs) therapy and tissue regeneration. To address this challenge, an immuno-piezoelectric transducer have been developed to create an anti-inflammatory immune microenvironment, deliver wireless electrical stimulation, and facilitate multimodal NSCs therapy. The immuno-piezoelectric transducer drives the polarization of microglia towards the anti-inflammatory M2 phenotype and secretion of anti-inflammatory cytokines. This modulation significantly reduces the inflammatory response, creating an optimal microenvironment for NSCs survival. Furthermore, the wireless electrical stimulation generated by ultrasound facilitates NSCs differentiation into glutamatergic and GABAergic neurons, enhances neurite complexity, upregulates synaptic proteins expression and neural integration in injured regions. The multimodal therapy demonstrates superior outcomes in restoring structural integrity, improving functional, and enhancing behavioral action in TBI rat models. This study integrates piezoelectric with immunomodulation to reprogram the neuroimmune microenvironment, providing novel therapeutic paradigm for brain injury repair.

CAS / MDL: 1310-65-2 57-13-6
研究领域: 神经科学 · 免疫学 · 生物医学工程 · 干细胞治疗 · 转化神经病学 · 组织工程 · 生物材料
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Eco-friendly taro stem-sourced cellulose/polypyrrole hybrid aerogel: An efficient capture strategy for microplastics removal

Wei-peng Qiu,Hai-ze Su,Hao Su,Shao-hua Luo,Li-shan Lai,Jia-le Zhu,Zhen-lin Xu,Hong Wang,Peng Wen

The escalating issue of microplastic pollution poses significant threats to food safety and human health. A porous biomass aerogel synthesized by in-situ growth of polypyrrole on the surface of waste taro stem cellulose-based aerogel was prepared for the adsorption and enrichment of microplastics from aqueous solutions and liquid food. The optimized TS-MCC/PPy 4.0 aerogel demonstrated exceptional mechanical strength (137.55 kPa) and outstanding polystyrene (PS) microplastics adsorption capacity, with q m being 818.06 mg/g at 298 K. The aerogel maintained robust applicability across varying pH conditions and ionic strengths, exhibiting superior adsorption efficiency (>80 %) for microplastics of varying sizes (200 nm to 2000 nm) and types (polyethylene (PE), polyethylene glycol terephthalate (PET), polypropylene (PP) and PS). Scanning electron microscope, fourier transform infrared spectrometer and X-ray photoelectron spectroscopy analysis identified multiple adsorption mechanisms: physical entrapment (PE, PP, PS, PET), hydrogen bonding (PE, PP, PS, PET), electrostatic interactions (PP, PS, PET), and π-π interactions (PS, PET). The adsorption efficiency was kept 91.55 ± 0.53 % for PS after 5 reuse cycles, complemented by favorable biocompatibility and complete soil biodegradation within 12 weeks. The aerogel demonstrated exceptional adsorption performance and recovery rates in four liquid food matrices application. This study presented an efficient and green cellulose-based aerogel adsorbent for microplastics removal.

CAS / MDL: 10025-77-1 109-97-7
研究领域: 环境科学 · 材料科学 · 污染控制 · 食品安全 · 纳米技术 · 可持续化学
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