ADVANCED FUNCTIONAL MATERIALS
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2024
·
IF 18.5
Huajing Zeng,Ziyan Chen,Pengyu Wei,Haofei Huang,Bin Liu,Zengjie Fan
3D printing of articular cartilage tissue faces challenges like replicating its complex structure, time-consuming in vitro stem cell culture, and a lack of robust in situ regeneration methods for osteochondral defects (OC). In response, an innovative approach utilizing pre-designed bioink modular units for one-step printing and immediate implantation is proposed, circumventing the need for prior in vitro stem cell cultivation. The resulting printed scaffold not only accurately reproduces the three-layer structure and material gradient of articular cartilage tissue but also attains impressive compressive strength (6.3 MPa) through the reinforcement of hydroxyapatite nanofibers and the establishment of chemical bonds with hydrogels. Moreover, the scaffold integrates stem cell capturing and homing layers on its bottom and top layers via chemical crosslinking aptamer and loading poly (lactic-co-glycolic acid) (PLGA) nanospheres encapsulated with stromal cell-derived factor-1α (SDF-1α), respectively. This design enables the specific capture of bone marrow mesenchymal stem cells (BMSCs) in vivo through aptamer interaction, followed by their mobilization to home in on the hyaline cartilage layer via the chemotaxis of SDF-1α concentration gradient. Within the scaffold's microenvironment, these BMSCs undergo differentiation into distinct cells for each layer, effectively contributing to the repair of OC defects in rabbits.
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高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Chuan Gao,Kun Yang,Jiahui She,Ruxiang Wang,Xiangfu Meng,Renyuan Sun,Yunjie Jin,Weihua Qiao,Jiawei Shi,Jianglin Wang,Nianguo Dong,Chao Xu,Donghui Zhang,Zhiqiang Luo
Heart valve organoids hold promise for modeling human valve biology, yet existing platforms often lack human-relevant cell sources, preserved multicellular architecture, and physiologic mechanical cues, limiting their capacity to recapitulate extracellular matrix (ECM) formation and structural maturation. Here, a strategy is established that integrates human induced pluripotent stem cell-derived valve interstitial cells (hiPS-VICs), spheroid organization, bio-printable hydrogels, and controlled mechanical conditioning to engineer advanced valve organoids. 3D bio-printing of hiPS-VIC spheroids is conducted within GelMA/ChSMA constructs, systematically compares spheroid-based bio-printing (SBB) with single-cell bio-printing (SCB), and establishes mechanically-stimulated spheroid-based bio-printing (MSSB) to guide ECM remodeling. Spheroid bioprinting preserved cell–cell organization and improved post-print structural integrity, resulting in substantially enhanced ECM deposition and assembly over time when compared with SCB. Superimposing physiologic loading further promoted cellular spreading and ECM deposition, accompanied by transcriptional signatures associated with matrix production, matrix stabilization, and mechano-responsive pathways. Together, this spheroid-based, mechanically matured, human iPSC valve organoid platform provides a robust and physiologically relevant system that supports ECM development and structural organization beyond dissociated-cell approaches, offering a scalable foundation for human valve biology research, disease modeling, and translational applications.
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高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Wangyu Bi,Shanglin Cai,Liping Zhou,Jinglei Zheng,Yanxin Cui,Yingxian Li,Shuting Liu,Hongyu Chen,Shuang Sha,Jiaxin Li,Qiansu Ma,Zhaoshi Bao,Cencan Xing,Hongwu Du,Lei Wang
3D culture of mesenchymal stem cells (MSCs) more effectively supports spheroid formation and sustained growth factor secretion, creating a microenvironment conducive to neural differentiation compared to traditional monolayer culture. However, challenges in long-term culture, including heterogeneity, central necrosis, and scalability, hinder its application in neural regeneration therapies. This study presents an automated microfluidic hydrogel-enhanced spheroid formation and maintenance array (M-HESMA) chip, combining a basement membrane-like hydrogel, microwell array, and dynamic culture system. The hydrogel, comprising a dual-network of Pluronic F-127-heparin (PF127-Hep) and crosslinked hyaluronic acid (XL-HA) with growth factors, supports spheroid formation and growth. The M-HESMA chip is validated using stem cells from human exfoliated deciduous teeth (SHEDs), forming uniform spheroids with minimal necrosis. The derived neurospheroids (MSNSs) exhibit enhanced neural differentiation and paracrine potential. Dissociated MSNSs (MSNS diss ) are applied to 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mice, improving motor function and reducing pathological symptoms compared to monolayer-cultured SHEDs treatment. MSNS diss -treated mice show increased brain-derived neurotrophic factor (BDNF) levels, phosphoinositide 3-kinase/protein kinase b (PI3K/Akt) pathway activation, and decreased neuronal apoptosis. The M-HESMA chip provides a scalable, efficient platform for spheroid generation, offering a promising approach for MSCs-based therapies targeting neurodegenerative diseases.
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Cardiovascular Diabetology
·
2025
·Vol. 24
·期 1
·1-16
·
IF 10.6
Liu Libo,An Ziyu,Zhang Huan,Wan Xueqi,Zhao Xin,Yang Xueyao,Tian Jinfan,Song Xiantao
IntroductionBone marrow-derived mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) are widely used for therapeutic purposes in preclinical studies. However, their utility in treating diabetes-associated atherosclerosis remains largely unexplored. Here, we aimed to characterize BMSC-EV-mediated regulation of autophagy and macrophage polarization.Methods EVs were isolated from the supernatant of cultured BMSCs and characterized with transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting. A diabetes-related atherosclerotic ApoE−/− mouse model was established through feeding with a high-fat diet (HFD) and streptozotocin (STZ). Histopathological analyses were carried out using Oil Red O, H&E, and Masson staining of the aorta. TEM and immunohistochemistry (IHC) were applied to evaluate autophagy, and immunofluorescence (IF) was used to identify macrophage polarization. RAW264.7 macrophages were induced with oxidized low-density lipoprotein (ox-LDL) and high glucose (HG), co-cultured with BMSC-EVs, and analyzed for macrophage proliferation, migration, and foam cell formation. RAW264.7 cells were transduced with autophagy marker mRFP-GFP-LC3 lentivirus and analyzed with IF and western blotting.Results Diabetic mice (DA group) had larger aortic plaque areas and lower collagen content than the HFD mice. BMSC-EV treatment significantly reduced blood glucose, LDL levels, and aortic plaque areas while increasing collagen content. BMSC-EV-treated aortas contained a higher number of autophagosomes/autolysosomes, with increased expression of LC3BII correlating with decreased P62 levels and a lower proportion of M1 macrophages. In vitro, BMSC-EVs inhibited proliferation, migration, and foam cell formation in ox-LDL and HG-induced activated RAW264.7 cells. These effects were reversed by the autophagy blocker bafilomycin A1. Consistent with the in vivo findings, BMSC-EVs elevated levels of the autophagy-related protein LC3BII/I and decreased P62 in ox-LDL and HG-induced RAW264.7 cells. These cells also expressed the M1 macrophage markers CD86 and iNOS, but showed reduced expression of the M2 marker Arg-1. Further, BMSC-EVs decreased AMPKα and mTOR phosphorylation levels, which were blocked by the AMPK inhibitor compound C.Conclusion sBMSC-EVs attenuate diabetes-exacerbated atherosclerosis by inhibiting vascular macrophage proliferation, migration, and foam cell formation via AMPK/mTOR signaling-regulated autophagy and macrophage polarization. BMSC-EVs thus hold promise as therapeutic agents for atherosclerosis.Graphical Extracellular vesicles derived from bone marrow mesenchymal stem cells may mitigate diabetes-aggravated atherosclerosis by regulating AMPK/mTOR-mediated autophagy-related macrophage polarization and inhibiting macrophage proliferation, migration, foam cell formation, and cholesterol transport.
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PubMed
高影响因子
CELL AND TISSUE RESEARCH
·
2023
·
IF 3.6
Yuan Haojie,Yu Junbo,Liu Chun,Zhao Heyan,Xue Jianhua,Liu Jiajia,Yang Yang
This study aims to discuss the role of exosomes KCNQ10T1 derived from bone marrow mesenchymal stem cells (BMMSCs) in sepsis and to further investigate its potential molecular mechanisms. Exosomes extracted from BMMSCs are identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot. Fluorescence labeling is applied to detect the internalization of exosomes in receptors. The proliferation ability, migration ability, and invasion ability of HUVECs are determined by CCK-8, EdU, wound healing, and Transwell. The levels of inflammatory cytokines in sepsis cells are quantitatively detected by ELISA. Kaplan–Meier survival curve is used to describe the overall survival. RT-qPCR is used to detect mRNA expression of related genes. Bioinformatics analysis is performed to search the downstream target of KCNQ1OT1 and miR-154-3p and the interaction is verified by luciferase reporter assay. Exosomes derived from BMMSCs alleviated the toxicity in sepsis cell models and animal models. In mice with septic cell models, exosomal KCNQ10T1 was down-regulated and associated with lower survival. Overexpression of KCNQ10T1 inhibited the proliferation and metastasis of LPS-induced HUVECs. Further research illustrated that miR-154-3p was the downstream target gene of KCNQ1OT1 and RNF19A was the downstream target gene of miR-154-3p. Importantly, functional research findings indicated that KCNQ1OT1 regulated sepsis progression by targeting miR-154-3p/RNF19A axis. Our study demonstrates that the exosomal KCNQ1OT1 suppresses sepsis via mediating miR-154-3p/RNF19A, which provides a latent target for sepsis treatment.
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PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2014
·Vol. 8
·期 3
·935-942
·
IF 0.941
Wei Zhang,Jiabo Hu,Quanhui Ma,Sanqiang Hu,Yanyan Wang,Xiangmei Wen,Yongbin Ma,Hong Xu,Hui Qian,Wenrong Xu
An immortalized mouse fetal liver stromal cell line, named KM3, has demonstrated the potential to support the growth and maintenance of human embryonic stem cells (hESCs). In this study, the characteristics of KM3 cells were examined following cryopreservation at -70˚C and in liquid nitrogen for 15, 30 and 60 days following treatment with 10 µg/ml mitomycin C. In addition, whether the KM3 cells were suitable for use as feeder cells to support the growth of hESCs was evaluated. The inhibition of mitosis without cell death was observed when the KM3 cells were treated with 10 µg/ml mitomycin C for 2 h. The morphology of the KM3 cells cryopreserved in liquid nitrogen for 60 days was not markedly changed, and the cell survival rate was 84.60±1.14%. By contrast, the survival rate of the KM3 cells was 66.40±2.88% following cryopreservation at -70˚C for 60 days; the cells readily detached, were maintained for a shorter time, and had a reduced expression level of basic fibroblast growth factor. hESCs cultured on KM3 cells cryopreserved in liquid nitrogen for 60 days showed the typical bird's nest structure, with clear boundaries and a differentiation rate of 16.33±2.08%. The differentiation rate of hESCs cultured on KM3 cells cryopreserved at -70˚C for 60 days was 37.67±3.51%. These results indicate that the cryopreserved KM3 cells treated with mitomycin C may be directly used in the subculture of hESCs, and the effect is relatively good with -70˚C short-term or liquid nitrogen cryopreservation.
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高影响因子
Nanoscale
·
2018
·Vol. 10
·期 41
·19579-19585
·
IF 7.233
Zheng Guo,Xiaohua Zhu,Shigong Wang,Chunyang Lei,Yan Huang,Zhou Nie,Shouzhuo Yao
As an emerging two-dimensional material, MXenes have attracted much attention due to their unique physicochemical properties, but their application in biosensing has been lagging far behind because of their poor salt tolerance. Herein, a titanium carbide MXene quantum dot (Ti3C2 QD)-based fluorescent probe for the alkaline phosphatase (ALP) activity assay and embryonic stem cell (ESC) identification was developed by taking advantage of the inner filter effect (IFE). Ti3C2 QDs with ∼4.2 nm in diameter were prepared from Ti3C2 MXenes by hydrothermal treatment, exhibiting excellent salt tolerance, anti-photobleaching and dispersion stability in aqueous solution. Owing to the remarkable overlap between the absorption spectrum of p-nitrophenol (p-NP) and the excitation and emission spectrum of Ti3C2 QDs, p-NP generated from ALP-catalyzed dephosphorylation of the substrate, p-nitrophenyl phosphate (p-NPP), can effectively quench the fluorescence of Ti3C2 QDs through the IFE. As a result, sensitive fluorometric analysis of ALP activity was achieved without complicating the conventional colorimetric ALP detection system. The proposed assay was successfully applied to determine ALP activity with a low limit of detection (0.02 U L−1) as well as monitoring the enzyme activity in real time. Finally, accurate analysis of ALP, the biomarker of ESC, in ESC lysates was also achieved using this IFE-based method, affording an alternative method for ESC identification.
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高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Jiankun Guan,Yuxin Wu,Xin Liu,Huimin Wang,Ningbing Ye,Zheng Li,Chen Xiao,Zhijie Zhang,Zifu Li,Xiangliang Yang
Cancer stem cells (CSCs) present grand challenges for triple-negative breast cancer (TNBC). Conventional chemotherapy drugs, including Camptothecin (CPT), not only cannot eradicate CSCs but also foster a suppressive immune microenvironment for the initiation and proliferation of CSCs. Herein, we report a novel prodrug CPT–SS–NLG919 (CN) and its nanoformulation [email protected] ( [email protected] ), which potently suppress CSCs by regulating CSCs niche in murine TNBC 4T1 tumors. Via inducing immunogenic cell death (ICD) and simultaneous inhibiting indoleamine 2, 3-dioxygenase (IDO), CN and [email protected] promote DC maturation, decrease Treg cells, mitigate tryptophan consumption, and reduce the amount of IL-6, IL-13, and TGF-β, converting CSCs niche to a hostile condition for CSCs to live in and eliminating CSCs efficiently, thereby inducing efficient tumor inhibition in 4T1 tumor models. Our work represents a new paradigm of eliminating CSCs by regulating tumor immune microenvironment and suggests that CN and its nanoformulation [email protected] are promising candidates for the treatment of intractable TNBC.
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高影响因子
Stem Cell Research & Therapy
·
2020
·Vol. 11
·期 1
·1-15
·
IF 5.116
Shen Ying-Shan,Chen Xiao-Jun,Wuri Sha-Na,Yang Fan,Pang Feng-Xiang,Xu Liang-Liang,He Wei,Wei Qiu-Shi
Objectives Polydatin (PD), extracted from Polygonum cuspidatum , has shown potential therapeutic applications due to its antiosteoporotic and anti-inflammatory activities. Our previous study suggested that PD promotes the osteogenesis of human bone marrow stromal cells (hBMSCs) via the BMP2-Wnt/β-catenin pathway. The aim of our present study was to further explore the role of PD-mediated regulation of Tafazzin (TAZ), a transcriptional coactivator with a PDZ-binding motif, in osteogenesis. Materials and methods hBMSCs were isolated and treated with PD at various concentrations. Alizarin red staining and RT-qPCR were performed to identify calcium complex deposition in hBMSCs as well as the expression of specific osteoblast-related markers, respectively, in each group. Next, TAZ-silenced hBMSCs were generated by lentivirus-produced TAZ shRNA. After treatment with PD, the osteogenic abilities of the TAZ-silenced and control hBMSCs were estimated by ALP activity assay, and expression of the TAZ protein was detected by Western blot analysis and immunofluorescence staining. In vitro, an ovariectomized (OVX) mouse model was established and used to evaluate the effect of PD on bone destruction by micro-CT, immunohistochemistry, and ELISA. Results In vitro, 30 μM PD significantly improved the proliferation and calcium deposition of hBMSCs and markedly stimulated the expression of the mRNAs RUNX2 , Osteopontin , DLX5 , β-catenin , TAZ , and Osteocalcin ( OCN ). Osteogenic differentiation induced by PD was blocked by lentivirus-mediated TAZ shRNA. Furthermore, Noggin (a regulator of bone morphogenic protein 2 (BMP2)) and DKK1 (an inhibitor of the Wnt/β-catenin pathway) were found to inhibit the increase in TAZ expression induced by PD. In vivo, PD prevented estrogen deficiency-induced bone loss in the OVX mouse model. Conclusion Taken together, our findings suggest that PD improved the osteogenic differentiation of hBMSCs and maintained the bone matrix in the OVX mouse model through the activation of TAZ, a potential target gene of the BMP2-Wnt/β-catenin pathway.
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高影响因子
Bioactive Materials
·
2020
·
IF 8.724
Yantao Zheng,Gang Wu,Limei Chen,Ying Zhang,Yuwei Luo,Yong Zheng,Fengjun Hu,Tymor Forouzanfar,Haiyan Lin,Bin Liu
Brain tissues that are severely damaged by traumatic brain injury (TBI) is hardly regenerated, which leads to a cavity or a repair with glial scarring. Stem-cell therapy is one viable option to treat TBI-caused brain tissue damage, whose use is, whereas, limited by the low survival rate and differentiation efficiency of stem cells. To approach this problem, we developed an injectable hydrogel using imidazole groups-modified gelatin methacrylate (GelMA-imid). In addition, polydopamine (PDA) nanoparticles were used as carrier for stromal-cell derived factor-1 (SDF-1α). GelMA-imid hydrogel loaded with [email protected] α nanoparticles and human amniotic mesenchymal stromal cells (hAMSCs) were injected into the damaged area in an in-vivo cryogenic injury model in rats. The hydrogel had low module and its average pore size was 204.61 ± 41.41 nm, which were suitable for the migration, proliferation and differentiation of stem cells. In-vitro cell scratch and differentiation assays showed that the imidazole groups and SDF-1α could promote the migration of hAMSCs to injury site and their differentiation into nerve cells. The highest amount of nissl body was detected in the group of GelMA-imid/SDF-1α/hAMSCs hydrogel in the in-vivo model. Additionally, histological analysis showed that GelMA-imid/SDF-1α/hAMSCs hydrogel could facilitate the regeneration of regenerate endogenous nerve cells. In summary, the GelMA-imid/SDF-1α/hAMSCs hydrogel promoted homing and differentiation of hAMSCs into nerve cells, and showed great application potential for the physiological recovery of TBI.
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高影响因子
American Journal of Translational Research
·
2019
·
IF 3.266
Zhao Wang,Hong-Wei Bao
Our aim was to study the osteogenic effect of cnidium lactone for bone marrow mesenchymal stem cells (BMSCs) and its potential mechanism. BMSCs were isolated and identified by flow cytometry and multidirectional differentiation capacity. Cell Counting Kit-8 (CCK-8) was used to identify the optimal concentration of cnidium lactone. Alkaline Phosphatase (ALP) and Alizarin Red S (ARS) was performed to identify whether cnidium lactone has effect on osteogenesis at early and late phase respectively. Moreover, we used estrogen receptor antagonist, ICI182780, to identify the receptor of cnidium lactone. The expression of Runt-related transcription factor 2 (RUNX2), Osterix (OSX), osteopontin (OPN), estrogen receptor (ER), Smad4, p-Smad1, Smad1 and bone morphogenetic protein 2 (BMP-2) protein were measured by PCR and western blot. Cnidium lactone (2 μM) demonstrated increased osteogenesis after osteogenic inducible medium (OIM) induction, as evidenced by more ALP activity and mineralization. When blocked with ICI182780, osteogenesis capacity was decreased. Moreover, the polymerase chain reaction (PCR) and western blotting results indicated that cnidium lactone enhanced ER, BMP2, Smad1, Smad4, RUNX2, OSX, and OPN expression and Smad1 phosphorylation. Cnidium lactone can effectively stimulates osteogenic differentiation of BMSCs via BMP-2/Smad-Signaling cascades mediated by ER.
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高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Dun Liu,Geng Lu,Bo Shi,Huanyu Ni,Jun Wang,Yong Qiu,Lin Yang,Zezhang Zhu,Xuan Yi,Xiao Du,Benlong Shi
Although stem cell-based therapy is recognized as a promising therapeutic strategy for spinal cord injury (SCI), its efficacy is greatly limited by local reactive oxygen species (ROS)-abundant and hyper-inflammatory microenvironments. It is still a challenge to develop bioactive scaffolds with outstanding antioxidant capacity for neural stem cells (NSCs) transplantation. In this study, albumin biomimetic cerium oxide nanoparticles (CeO 2 @BSA nanoparticles, CeNPs) are prepared in a simple and efficient manner and dispersed in gelatin methacryloyl to obtain the ROS-scavenging hydrogel (CeNP-Gel). CeNP-Gel synergistically promotes neurogenesis via alleviating oxidative stress microenvironments and improving the viability of encapsulated NSCs. More interestingly, in the presence of CeNP-Gel, microglial polarization to anti-inflammatory M2 subtype are obviously facilitated, which is further verified to be associated with phosphoinositide 3-kinase/protein kinase B pathway activation. Additionally, the injectable ROS-scavenging hydrogel is confirmed to induce the integration and neural differentiation of transplanted NSCs. Compared with the blank-gel group, the survival rate of NSCs in CeNP-Gel group is about 3.5 times higher, and the neural differentiation efficiency is about 2.1 times higher. Therefore, the NSCs-laden ROS-scavenging hydrogel represents a comprehensive strategy with great application prospect for the treatment of SCI through comprehensively modulating the adverse microenvironment.
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高影响因子
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