Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 13
·2673-2688
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IF 5.344
Huanhuan Yan,Yu Wang,Linlong Li,Xiaosong Zhou,Xincui Shi,Yen Wei,Peibiao Zhang
An effective treatment for spinal cord injury (SCI) remains a severe clinical challenge due to the intrinsically limited regenerative capacity and complex anatomical structure of the spinal cord. The combination of biomaterials, which serve as scaffolds for axonal growth, cells and neurotrophic factors, is an excellent candidate for spinal cord regeneration. Herein, a new micropatterned conductive electrospun nanofiber mesh was constructed with poly{[aniline tetramer methacrylamide]-co-[dopamine methacrylamide]-co-[poly(ethylene glycol) methyl ether methacrylate]}/PCL (PCAT) using a rotation electrospinning technology. The aim was to study the synergistic effects of electrical stimulation (ES) and a micropatterned conductive electrospun nanofiber mesh incorporated with nerve growth factor (NGF) on the differentiation of rat nerve stem cells (NSCs). The hydrophilicity of the conductive nanofiber mesh could be tailored by changing the dopamine (DA) and aniline tetramer (AT) content from 19° to 79°. A favorable electroactivity and conductivity was achieved by the AT segment of PCAT. The as-fabricated micropatterned electrospun nanofiber mesh possessed a regularly aligned valley and ridge structure, and the diameter of the nanofiber was 312 ± 58 nm, while the width of the valley and ridge was measured to be 210 ± 17 μm and 200 ± 16 μm, respectively. The growth and neurite outgrowth of differentiated NSCs were observed along the valley of the micropatterned nanofiber mesh. In addition, the NGF loaded micropatterned conductive electrospun nanofiber mesh combined with ES exhibited the highest cell viability, and effectively facilitated the differentiation of NSCs into neurons and suppressed the formation of astrocytes, thus exhibiting a great application potential for nerve tissue engineering.
研究领域:
组织工程
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神经科学
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生物材料
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再生医学
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PubMed
高影响因子
Applied Materials Today
·
2021
·
IF 10.041
Zhijun Lin,Bolong Liu,Haixia Wang,Hailun Zhan,Yong Huang,Jianxi Lu,Yu Tao,Mingqiang Li,Xiangfu Zhou
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a critical disease characterized by debilitating pelvic pain associated with lower urinary tract symptoms. Effective therapeutic strategies remain challenging due to their elusive pathogenesis. Mesenchymal stem cell (MSC) therapy offers a promising therapeutic approach for IC/BPS treatment. Yet, the ethical arguments and tumorigenic risks from cell therapy by stem cells restrict the clinical application. Herein, we developed a nanoparticle that encapsulates the conditioned medium (CM) from stem cells and coated with cationic N-trimethyl chitosan chloride (TMC) on the surface to improve the penetration of epithelial barrier in intravesical therapy for IC/BPS. The TMC coating enhanced the accumulation of CM-loaded nanoparticles in the urothelium and subsequently improved the therapeutic efficacy on the mechanical threshold and micturition function through facilitating the effect of anti-inflammation and BDNF/TrkB signaling, which provides a great potential application on the transmucosal delivery platform for intravesical therapy of IC/BPS.
研究领域:
药学
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干细胞生物学
·
泌尿学
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DOI
高影响因子
Biomed Research International
·
2016
·
IF 2.134
Gai Xue,Xiaolei Han,Xin Ma,Honghai Wu,Yabin Qin,Jianfang Liu,Yuqin Hu,Yang Hong,Yanning Hou
Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are considered to be an ideal cell source for cell therapy of many diseases. The aim of this study was to investigate the contribution of the microenvironment to the hepatic differentiation potential of hUCMSCs in vitro and in vivo and to explore their therapeutic use in acute liver injury in rats. We established a new model to simulate the liver tissue microenvironment in vivo using liver homogenate supernatant (LHS) in vitro. This induced environment could drive hUCMSCs to differentiate into hepatocyte-like cells within 7 days. The differentiated cells expressed hepatocyte-specific markers and demonstrated hepatocellular functions. We also injected hUCMSCs into rats with CCl4-induced acute hepatic injury. The hUCMSCs were detected in the livers of recipient rats and expressed the human hepatocyte-specific markers, suggesting that hUCMSCs could differentiate into hepatocyte-like cells in vivo in the liver tissue microenvironment. Levels of biochemistry markers improved significantly after transplantation of hUCMSCs compared with the nontransplantation group (). In conclusion, this study demonstrated that the liver tissue microenvironment may contribute to the differentiation of hUCMSCs into hepatocytes both in vitro and in vivo.
研究领域:
干细胞生物学
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肝病学
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细胞治疗
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再生医学
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PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Jinming Li,Qingxin Zhao,Jiani Sun,Hao Zeng,Anli Yang
Spatiotemporally precise control of mesenchymal stem cells (MSCs) differentiation remains an unmet challenge in regenerative medicine. Herein, we report a near-infrared (NIR)-responsive platform that integrates upconversion nanoparticle (UCNP)-functionalized substrates with host-guest photoresponsive chemistry (β-cyclodextrin/arylazopyrazole-RGD) to NIR spatiotemporally orchestrate MSCs adhesion, spreading, and lineage commitment with spatiotemporal precision. The UCNPs convert 808 nm NIR light into localized UV emissions, dynamically modulating azobenzene-cyclodextrin interactions and thereby tuning surface RGD ligand density via photoisomerization. Under low NIR intensities (0–0.5 W/cm 2 ), augmented integrin-RGD binding drives robust focal adhesion assembly, actin cytoskeletal tension, nuclear YAP translocation, and osteogenic differentiation, as evidenced by 2–3 fold upregulation of BMP2, RUNX2, and ALP. Conversely, high-intensity NIR (1–2 W/cm 2 ) induces RGD detachment, leading to suppressed cytoskeletal contractility and nuclear Lamin A/C expression, consequent cytoplasmic YAP retention, and activation of PPARγ-mediated adipogenesis, marked by 4–5 fold induction of PPARγ, C/EBPα, and FABP4. Most importantly, in vivo murine studies validate the platform's capacity for non-invasive, light-guided spatiotemporal regulation of MSCs adhesion, spreading, YAP signaling, and lineage specification (osteogenic vs. adipogenic), wherein differentiation thresholds (e.g., 1 W/cm 2 ) correspond to clinically safe NIR exposure limits. This opto-material hybrid system effectively decouples photochemical stimulation to program MSC fate via mechanotransduction pathways, thereby providing a translatable strategy for the design of intelligent biomaterials towards personalized tissue regeneration.
研究领域:
再生医学
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生物材料学
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组织工程
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细胞力学转导
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光响应治疗
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干细胞生物学
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产品关联
DOI
PubMed
高影响因子
BIOCELL
·
2026
·Vol. 50
·期 6
·
IF 1.8
Junming Yan,Boran Xiong,Yingjie Zhu
Objective: Neural stem cells (NSCs) are essential for replenishing nerve cells, providing neuroprotection, and repairing damaged brain function, while mitophagy is critical for maintaining NSCs’ homeostasis. The study investigated whether pyruvate kinase M2 (PKM2) regulates NSCs’ proliferation and differentiation by modulating mitophagy. Method: This study established a model of excessive autophagy in neural stem cell mitochondria induced by cobalt chloride (CoCl 2 ) and used plasmid transfection technology to knock down PKM2 expression, examining its effects on NSCs proliferation and differentiation. Additionally, potential mechanisms were explored by overexpressing phosphatase and tensin homolog-induced putative kinase 1 (PINK1) and adding the mitophagy inducer carbonyl cyanide m-chlorophenyl hydrazone (CCCP). Result: Treatment with CoCl 2 significantly inhibited the proliferation of NSCs and their differentiation into neurons, induced excessive mitophagy, and activated the PKM2/PINK1/Parkin pathway. Knockdown of PKM2 markedly enhanced cell viability, promoted NSCs’ proliferation, and neuronal differentiation. Mechanistically, PKM2 knockdown not only decreased the protein levels of PINK1, Parkin, p-Parkin, Beclin1, and LC3 II/I but also increased p62 expression, thereby mitigating excessive mitophagy. Overexpression of PINK1 attenuated the inhibitory effect of PKM2 knockdown on CoCl 2 -induced mitophagy in NSCs. Moreover, PKM2 knockdown significantly reversed the detrimental effects of CCCP on mitochondrial function, cell survival, and neuronal differentiation, further confirming that PKM2 promotes NSC proliferation and neuronal differentiation by inhibiting mitophagy. Conclusion: Knocking down PKM2 could inhibit PINK1/Parkin-mediated excessive mitophagy, thereby promoting NSCs proliferation and neuronal differentiation.
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Sustainable Materials and Technologies
·
2026
·
IF 9.7
Chenxiao Zheng,Feifan Luan,Yue Ying,Yurui Wu,Chunwei Wei,Jiayi Chen,Yanzhen Lou,Kailong Zhang,Guohua Jiang
Osteoarthritis (OA) treatment currently lacks an effective integration of mechanical protection and biological repair. The present study aimed to design a stem cell delivery system that combines a biomimetic synovial fluid with human umbilical cord mesenchymal stem cells (Uc-MSCs) for the synergistic treatment of OA. Firstly, an injectable lubricant was prepared by the combination of polyacrylic acid amphiphilic ionomer (PG) and mussel adhesive protein (MAP). Uc-MSCs were incorporated into this matrix to form a biomimetic synovial fluid (Uc-MSCs@PG/MAP). The lubrication performance, antioxidant capacity, and cytocompatibility of Uc-MSCs@PG/MAP were assessed, revealing excellent lubrication, reactive oxygen species (ROS) scavenging ability, and the capacity to maintain stem cell viability. The as-developed synovial fluid not only enhances joint lubrication but also functions as a carrier for the delivery of umbilical cord - derived mesenchymal stem cells. In vivo experimental results indicate that it reduces early-stage stress through hydrodynamic lubrication and promotes late-stage cartilage regeneration via stem cell differentiation and paracrine signaling. This combined approach significantly outperforms monotherapies by inhibiting matrix metalloproteinase-13 (MMP-13) and pro-inflammatory cytokines (TNF-αand IL-6). This strategy successfully integrates “mechanical lubrication” with “biological regeneration,” presenting a highly translatable and minimally invasive solution for the management of OA.
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Plants-Basel
·
2026
·Vol. 15
·期 3
·483
·
IF 4.7
Huagang Huang,Jinsong He,Denglu Liu,Haiying Yu,Lu Zhang,Tao Liu
Tobacco (Nicotiana tabacumL.) has a propensity to accumulate cadmium (Cd), especially in its leaves, which can have a detrimental impact on yield, quality, and product safety. The development of low-accumulation cultivars is a vital mitigation approach; however, the underlying mechanisms remain inadequately understood. In this study, through pot experiments, the physiological mechanisms responsible for the differential Cd accumulation between the low-accumulating tobacco line CF986 and the high-accumulating Yuyan5 were explored. A comprehensive analysis was conducted on the organ-specific Cd distribution, chemical speciation, subcellular compartmentalization, and photosynthetic responses across a gradient of Cd exposure. In comparison with Yuyan5, CF986 accumulated significantly higher amounts of Cd in the roots and stems, but substantially lower amounts in the leaves. Specifically, the Cd content in the leaves of CF986 was only 64.32–68.74% of that in Yuyan5 across different Cd exposure levels. The organ-specific Cd distribution pattern in CF986 followed the order: leaf > stem > root. Moreover, the proportion of Cd partitioned to the leaves was lower in CF986 compared to Yuyan5, while the roots and stems exhibited enhanced Cd retention, with Cd levels in stems reaching up to 2.04 times higher than those in Yuyan5. Analysis of the chemical forms and subcellular distribution of Cd indicated that the mobile Cd fractions in the stems of CF986 were significantly reduced compared to Yuyan5. A larger proportion of Cd was immobilized in the stem cell-wall fraction, which enhanced Cd retention and restricted xylem-mediated transport to the leaves. Cd exposure did not significantly affect the concentration of foliar photosynthetic pigments in CF986; however, it notably inhibited the activity of the photosystem II (PSII) reaction center. At higher Cd levels, the photoprotective thermal dissipation gradually failed, with a decrease of up to 41.36% in ΦNOfor CF986 compared to CK under Cd4.0 treatment. This research unveiled a stem barrier mechanism, whereby Cd translocation to the leaves is restricted through chemical and subcellular sequestration in the stem. This mechanism provides a novel perspective on both plant heavy metal allocation and the assurance of crop safety.
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DOI
PubMed
高影响因子
Advanced Science
·
2026
·
IF 14.1
Xiaochen Feng,Ying Fang,Hongwei Yu,Yicheng Wang,Yunze Xu,Chunxiao Shi,Haike Xia,Ranjith Kumar Kankala,Aizheng Chen,Shibin Wang,Chaoping Fu
Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, chronic inflammation, and subchondral bone remodeling. Conventional intra-articular therapies provide limited relief and fail to address its multifactorial pathogenesis. Here, we present an injectable hydrogel microsphere platform that integrates antioxidative, anti-inflammatory, and regenerative functions for localized OA management. Uniform (∼125 µm) chondroitin sulfate methacrylate (ChSMA)-based microspheres are fabricated via microfluidic photocross-linking. Manganese dioxide nanoparticles provided catalytic reactive oxygen species (ROS) scavenging, while dexamethasone sodium phosphate enabled sustained release, reducing TNF-α and IL-6 levels by ∼30%. Bone marrow mesenchymal stem cells (BMSCs) are co-delivered to promote cartilage repair. In vitro, the microspheres reduce intracellular ROS, induce M2 macrophage polarization, and suppress inflammatory cytokines by 60–70%, with IL-10 levels increased by ∼90%. 3D co-culture supports chondrocyte/BMSC viability and matrix production. In vivo, intra-articular injection in a rat OA model markedly reduces cartilage erosion, decreases osteophyte volume by 80%, and improves subchondral bone microarchitecture. Histological staining confirms matrix restoration and structural preservation, with Osteoarthritis Research Society International (OARSI) scores reduced by 88%. Collectively, this injectable hydrogel microsphere system offers a minimally invasive and integrated strategy, simultaneously delivering antioxidative, anti-inflammatory, and regenerative effects for comprehensive OA management.
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2026
·
IF 5.6
Boyu Cai,Zhao Wang,Maoxiang Xu,Jiaojiao Li,Danni Li,Fei Tan
MSC-sEV attenuate eosinophilic nasal inflammation and mucosal remodeling in vivo. • MSC-sEV restore splenic Th1 and reduce Th17 cells, rebalancing T-helper responses. • MSC-sEV attenuate EMT-like changes and epithelial barrier dysfunction in ECRS. • RNA-seq and immunoblot link MSC-sEV effects to IL-17, TNF and JAK-STAT signaling. • Intranasal MSC-sEV offers a cell-free nanotherapy for refractory ECRS. Eosinophilic chronic rhinosinusitis (ECRS) is a refractory subtype characterized by dominant Th2 inflammation and progressive tissue remodeling, with high postoperative recurrence and limited efficacy of current biological agents. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) represent a promising cell-free nanotherapeutic approach, yet their efficacy in ECRS remains poorly studied. This study investigated the therapeutic efficacy of intranasal MSC-sEV against Th2/Th17 immune dysregulation and mucosal remodeling in a papain-induced ECRS model. Intranasal administration of MSC-sEV during the challenge phase significantly alleviated clinical symptoms and attenuated key pathological features, including epithelial hyperplasia, goblet cell hyperplasia, excessive mucus secretion and mucosal eosinophil infiltration, the latter confirmed by direct eosinophil quantification on H& E -stained sections. Immunohistochemistry showed that MSC-sEV attenuated airway remodeling by downregulating markers such as FXIII-A and CLCA1 while partially restoring E-cadherin levels, indicating attenuation of EMT-like changes. Flow cytometry of splenic lymphocytes revealed that MSC-sEV partially restored the disturbed systemic Th1/Th2/Th17 balance, with a more evident effect on the Th17-associated response, and immunohistochemistry for GATA3, IL-17 A and TNF-α confirmed concordant changes in the nasal mucosa. Transcriptomic analysis showed that these therapeutic effects were associated with downregulation of eosinophil-recruitment chemokines ( Ccl11 , Ccl24 ) and with reduced enrichment of IL-17, TNF and JAK-STAT signaling—corroborated at the protein level by decreased phosphorylation of STAT3 and NF-κB p65 and by RT-qPCR confirmation of nine key transcripts. Collectively, this study identifies MSC-sEV as an effective cell-free strategy that attenuates the development of ECRS by partially restoring immune homeostasis and attenuating epithelial remodeling. Download: Download high-res image (172KB) Download: Download full-size image
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CELL PROLIFERATION
·
2026
·
IF 7.6
Zhaosong Meng,Jiacheng Liu,Yue Zhang,Ruimeng Yang,Jingyi Zhang,Haosun Yang,Zheng Wang,Ran Wei,Zhe Li,Shuling Guo,Lizhi Hu,Lei Sui
Alveolar bone injury represents a prevalent clinical challenge in dentistry, for which stem cell-based therapy has emerged as a promising strategy to promote bone regeneration. N-acetylcysteine (NAC), a potent antioxidant, has been shown to modulate the PI3K-AKT signalling pathway and potentially enhance osteogenesis; however, the specific downstream effectors mediating this process remain unidentified. In this study, post-extraction serum metabolomic profiling revealed that alveolar bone injury is accompanied by systemic oxidative stress and metabolic remodelling. Transcriptomic analysis of antioxidant-treated dental stem cells further identified type VI collagen A1 (COL6A1) as a key functional mediator. We subsequently investigated the role of COL6A1 in antioxidant-mediated osteogenesis through immunofluorescence and protein assays, and performed knockdown and in vivo experiments to evaluate its function in oxidative stress regulation and osteogenic differentiation. Our results demonstrated that alveolar bone injury is associated with systemic oxidative stress and global metabolic alterations. In vitro, NAC markedly promoted the osteogenic differentiation of dental follicle stem cells (DFSCs) by activating the PI3K-AKT pathway and upregulating COL6A1. COL6A1 knockdown resulted in elevated reactive oxygen species (ROS) levels, impaired mitochondrial function, and attenuated NAC-mediated osteogenesis. In vivo, NAC-treated DFSCs exhibited enhanced bone healing and extracellular matrix (ECM) deposition in a rat model of alveolar bone injury, effects that were mediated through COL6A1 upregulation. Collectively, these findings demonstrate that NAC enhances osteogenesis in DFSCs via the PI3K-AKT-COL6A1 axis, offering a promising antioxidant-based strategy for stem cell therapies in bone regeneration. Moreover, COL6A1 is essential for maintaining redox homeostasis and represents a potential therapeutic target for improving regenerative outcomes.
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DOI
PubMed
高影响因子
Materials Today Communications
·
2026
·
IF 4.9
Jia Ning,Zhen Wang,Xin Zhang,Changyi Li,Zhimin Zhou
Periodontitis is a chronic inflammatory disease that progressively destroys periodontal tissues and alveolar bone, posing a significant challenge for clinical regeneration. Tissue engineering strategies integrating stem cells, biomaterials, and bioactive agents hold promise for overcoming the limitations of current periodontal regenerative approaches. In this study, we developed an injectable PLGA composite microscaffold-based co-delivery system with a porous architecture for the combined delivery of icariin (ICA) and bone marrow-derived mesenchymal stem cells (BMSCs). ICA-loaded PLGA composite microscaffolds (ICA-PLGA) were fabricated by a double emulsion–solvent evaporation method, followed by fibrinogen (Fg) surface modification via electrostatic layer-by-layer assembly to generate ICA-PLGA-Fg microscaffolds with improved cell-adhesive properties. These porous microscaffolds exhibited sustained ICA release for up to 28 days and enhanced BMSC adhesion and spreading. In vitro, ICA-PLGA-Fg supported favorable cytocompatibility and enhanced osteogenic differentiation of BMSCs under inflammatory conditions. In vivo, BMSC-seeded ICA-PLGA-Fg constructs implanted into rat periodontitis-related alveolar bone defects achieved markedly greater bone regeneration compared with both periodontitis and PLGA-only controls. Collectively, this co-delivery platform integrates sustained ICA release with a bioactive, cell-supportive microscaffold interface, promotes osteogenic responses in vitro, and shows therapeutic promise for enhancing periodontal bone repair in vivo.
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Stem Cell Research & Therapy
·
2026
·Vol. 17
·期 1
·200
·
IF 7.8
Chen Qi,Chen Xiaolong,Yang Qu,Miao Xinxin,Yuan Jinghong,Ding Shuihua,Ding Rui,Cai Shenghao,Li Bin,Cheng Xigao
Background Intervertebral disc degeneration (IVDD) is characterized by progressive nucleus pulposus cell loss and extracellular matrix degradation, in which persistent oxidative stress plays a critical pathogenic role. Transplantation of nucleus pulposus–derived stem cells (NPSCs) is a promising therapeutic strategy, yet the hostile oxidative microenvironment severely compromises cell survival. Although cellular quiescence has been suggested to enhance stress tolerance, its regulatory mechanisms and relevance in NPSCs remain largely unexplored. Methods Oxidative stress was evaluated in human degenerated disc tissues, a rat needle-puncture degeneration model, and tert-butyl hydroperoxide–treated NPSCs in vitro. Proliferating and quiescent NPSCs were compared for reactive oxygen species (ROS) levels, apoptosis, viability, and transcriptomic profiles. Pathway enrichment analyses were performed to identify critical signaling mechanisms. Recombinant transforming growth factor-beta 3 (rhTGF-β3) was used to activate the pathway, while small interfering RNA targeting the transforming growth factor-beta receptor type 2 ( Tgfbr2 ) and the pharmacological inhibitor SB431542 were applied for pathway suppression. Functional assays, organ culture, and in vivo transplantation were conducted to assess cell survival and regenerative effects. Results Elevated oxidative stress was consistently observed across clinical, animal, and cellular models of disc degeneration. Quiescent NPSCs demonstrated enhanced resistance to oxidative injury, with reduced ROS accumulation, decreased apoptosis, and improved survival. Transcriptomic analyses revealed suppression of metabolic and P53-mediated apoptotic pathways, alongside marked activation of TGF-β/SMAD signaling. Activation of this pathway induced quiescence, reduced ROS levels, inhibited mitochondrial apoptotic signaling, and protected NPSCs from oxidative injury, whereas pathway inhibition abolished these protective effects. In both organ culture and in vivo transplantation models, quiescent and TGF-β–activated NPSCs exhibited superior survival and significantly improved disc structural preservation compared with proliferating or pathway-blocked cells. Conclusion Activation of the TGF-β/SMAD pathway induces NPSC quiescence and enhances oxidative stress tolerance by suppressing P53-dependent mitochondrial apoptosis. Pharmacological induction of quiescence represents a potential strategy to improve stem cell–based therapies for intervertebral disc degeneration.
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