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RSC Advances · 2016 ·Vol. 6 ·期 72 ·67778-67784 · IF 3.289

Mesenchymal stem cells in response to exposed rod-heights of TiO2 nanorod films

Fei Ge,Mengfei Yu,Jun Lin,Cuixia Yu,Wenjian Weng,Kui Cheng,Huiming Wang

Cellular responses are strongly sensitive to surface structure, so the optimization of the structures is essential in biomaterial research. In this work, the exposed nanorod-heights in TiO2 nanorod films were adjusted for enhancing cellular responses. The adjustment was realized by incorporating mesoporous bioactive glass (MBG) into the nanorod films via a sol–gel method. The exposed nanorod-heights in the films could be changed from the original ∼300 nm to ∼200 nm and ∼100 nm. The cellular responses on the nanostructured surfaces were evaluated through culturing mesenchymal stem cells (MSCs). The results showed that the films with shortened nanorod-heights had better cellular responses and could accelerate osteogenic differentiation and mineralization, and the films with 100 nm nanorod-height provided the best surface for cell growth. This is attributed to the nanostructure with the shortened nanorod-heights being well recognized by the cells, consequently the cells grew with a faster osteogenic differentiation through a strengthened BMP-smads signal pathway.

研究领域: 生物材料 · 纳米技术 · 干细胞生物学 · 组织工程
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Science Advances · 2026 ·Vol. 12 ·期 1 · IF 12.5

Dynamic adaptive coassembled sericin protein orchestrating stem cell development for nucleus pulposus regeneration

Xing Li,Yize Zhao,Peiyang Gu,Chengkun Zhao,Yujiang Fan,Xingdong Zhang,Chao Zhao,Peter X. Ma,Ganjun Feng,Yong Sun

The zonal structure of natural extracellular matrix (ECM) creates a dynamic microenvironment that regulates mechanical and biochemical signals to support stem cell development. Here, we engineered a dynamic adaptive protein gel by coassembling bioactive sericin with an amphiphilic tripeptide, forming a nucleus pulposus (NP)–like viscoelastic network with rapid stress relaxation. This coassembled protein gel sequentially activated integrin β3–mediated mechanotransduction, promoted cytoskeletal remodeling and Yes-associated protein nuclear translocation, and subsequently up-regulated bioactive factors and ECM synthesis to orchestrate stem cell development. Incorporation of kartogenin provided sustained chondrogenic cues, thereby promoting stem cell differentiation and preserving NP tissue integrity in vivo. Together, these findings establish a phase separation–driven, adaptive protein matrix that orchestrates both mechanical and biochemical signaling for robust intervertebral disc regeneration.

CAS / MDL: 4727-31-5
✓ 已验证 产品关联 DOI PubMed 高影响因子
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EMBO REPORTS · 2020 · IF 7.497

Lipoic acid rejuvenates aged intestinal stem cells by preventing age-associated endosome reduction

Gang Du,Yicheng Qiao,Zhangpeng Zhuo,Jiaqi Zhou,Xiaorong Li,Zhiming Liu,Yang Li,Haiyang Chen

The age-associated decline of adult stem cell function is closely related to the decline in tissue function and age-related diseases. However, the underlying mechanisms that ultimately lead to the observed functional decline of stem cells still remain largely unexplored. This study investigated Drosophila midguts and found a continuous downregulation of lipoic acid synthase, which encodes the key enzyme for the endogenous synthesis of alpha-lipoic acid (ALA), upon aging. Importantly, orally administration of ALA significantly reversed the age-associated hyperproliferation of intestinal stem cells (ISCs) and the observed decline of intestinal function, thus extending the lifespan of Drosophila. This study reports that ALA reverses age-associated ISC dysfunction by promoting the activation of the endocytosis–autophagy network, which decreases in aged ISCs. Moreover, this study suggests that ALA may be used as a safe and effective anti-aging compound for the treatment of ISC-dysfunction-related diseases and for the promotion of healthy aging in humans.

研究领域: 细胞生物学 · 衰老研究 · 干细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Materials Chemistry B · 2020 ·Vol. 8 ·期 30 ·6378-6389 · IF 5.344

Mesenchymal stem cell-derived microvesicles mediate BMP2 gene delivery and enhance bone regeneration

Zhuo Liang,Yue Luo,Yonggang Lv

A demineralized bone matrix (DBM) scaffold has good biocompatibility, low antigenicity, a natural porous structure and no cytotoxicity, and so it is an appropriate material for bone regeneration. However, osteoinductive growth factors are often removed during preparation, which destroys the osteoinductive capacity of the DBM scaffold. Biomaterials combined with gene therapy is a promising approach to effectively avoid this adverse side effect. This study develops a human bone morphogenetic protein 2 (hBMP2) gene-activated DBM scaffold to enhance the osteoinductive capacity of DBM and improve bone repair. Bone marrow mesenchymal stem cell (MSC)-derived microvesicles (MVs) were obtained, and polyethyleneimine (PEI) and human bone morphogenetic protein 2 (hBMP2) plasmids (phBMP2) were sequentially coated on the MVs by layer-by-layer (LBL) self-assembly to form an MVs–PEI/phBMP2 non-viral gene vector. Finally, the gene-activated scaffold (DBM/MVs–PEI/phBMP2) was prepared by loading MVs–PEI/phBMP2 onto a DBM scaffold. The experimental results show that the MVs–PEI/phBMP2 exhibits higher transfection efficiency and lower cytotoxicity to MSCs when the MVs/PEI weight ratio = 5, and could enhance the osteogenic differentiation of MSCs in vitro. Subcutaneous implantation into rats showed that the DBM/MVs–PEI/phBMP2 scaffold could efficiently enhance the deposition of: collagen fibers, osteocalcin, osteopontin and CD34 endogenous proteins. Rabbit femoral condyle defect experiments proved that the DBM/MVs–PEI/phBMP2 scaffold could significantly promote bone repair. This study presents a novel, highly efficient and low cytotoxicity gene delivery vector based on MVs. The gene-activated DBM scaffold based on MVs not only could promote bone formation but also angiogenesis, implying that this kind of gene-activated scaffold is a promising bone substitute material.

CAS / MDL: 3326-32-7
研究领域: 组织工程 · 再生医学 · 基因治疗 · 生物材料
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION · 2018 · IF 1.911

Culture of pyramidal neural precursors, neural stem cells, and fibroblasts on various biomaterials

Mo Li,Ying Wang,Jidi Zhang,Zheng Cao,Shuo Wang,Wei Zheng,Qian Li,Tianqi Zheng,Xiumei Wang,Qunyuan Xu,Zhiguo Chen

A combinatory approach using biomaterials together with cells may improve the efficacy of cell therapy for treatment of various diseases/indications. In the current study, we cultured pyramidal neural precursors (PNPs), neural stem cells (NSCs), and fibroblasts on different materials that included fibrin, collagen, hyaluronic acid (HA), sciatic nerves, and matrigel, to search for the most suitable biomaterial for culture of each cell type. Collagen was fabricated in both an aligned collagen-poly (lactic-co-glycolic acid) (PLGA) composite and an alveolate form; fibrin and hyaluronic acid were made in an aligned form only. Pyramidal neurons have strong projection ability and have potentials in neural circuit reconstruction. However, PNPs showed difficulty in attaching to and growing neurites on most of the materials tested, except for matrigel, in which neurite growth was observed in a three dimentional culture. NSCs and derivatives hold promise in treating neurological diseases. On aligned fibrin, NSCs could differentiate and grow neurites in a directional manner before fibrin was degraded in 2 days. On aligned collagen-PLGA, induced neural stem cells (iNSCs) could survive and differentiate for at least 2 weeks, but the neurites failed to extend in an aligned way. Fibroblast graft are useful in many indications, such as in skin burns. Fibroblasts generally grew better on the tested materials than did the neural cells, and fibroblasts could grow directionally on the aligned fibrin and scattered around on the alveolate collagen. The study provided information which may be used to further optimize the materials to support culture of each type of cells.

CAS / MDL: 1071-93-8
研究领域: 神经科学 · 再生医学 · 细胞生物学 · 生物材料学
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JOURNAL OF NANOBIOTECHNOLOGY · 2018 ·Vol. 16 ·期 1 ·1-15 · IF 5.294

Specific cancer stem cell-therapy by albumin nanoparticles functionalized with CD44-mediated targeting

Li Yuanyuan,Shi Sanjun,Ming Yue,Wang Linli,Li Chenwen,Luo Minghe,Li Ziwei,Li Bin,Chen Jianhong

Background Cancer stem cells (CSCs) are highly proliferative and tumorigenic, which contributes to chemotherapy resistance and tumor occurrence. CSCs specific therapy may achieve excellent therapeutic effects, especially to the drug-resistant tumors. Results In this study, we developed a kind of targeting nanoparticle system based on cationic albumin functionalized with hyaluronic acid (HA) to target the CD44 overexpressed CSCs. All-trans-retinoic acid (ATRA) was encapsulated in the nanoparticles with ultrahigh encapsulation efficiency (EE%) of 93% and loading content of 8.37%. TEM analysis showed the nanoparticles were spherical, uniform-sized and surrounded by a coating layer consists of HA. Four weeks of continuously measurements of size, PDI and EE% revealed the high stability of nanoparticles. Thanks to HA conjugation on the surface, the resultant nanoparticles (HA-eNPs) demonstrated high affinity and specific binding to CD44-enriched B16F10 cells. In vivo imaging revealed that HA-eNPs can targeted accumulate in tumor-bearing lung of mouse. The cytotoxicity tests illustrated that ATRA-laden HA-eNPs possessed better killing ability to B16F10 cells than free drug or normal nanoparticles in the same dose, indicating its good targeting property. Moreover, HA-eNPs/ATRA treatment decreased side population of B16F10 cells significantly in vitro. Finally, tumor growth was significantly inhibited by HA-eNPs/ATRA in lung metastasis tumor mice. Conclusions These results demonstrate that the HA functionalized albumin nanoparticles is an efficient system for targeted delivery of antitumor drugs to eliminate the CSCs.

CAS / MDL: 25952-53-8
研究领域: 肿瘤学 · 纳米技术 · 药学 · 分子生物学
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JOURNAL OF WUHAN UNIVERSITY OF TECHNOLOGY-MATERIALS SCIENCE EDITION · 2018 ·Vol. 33 ·期 6 ·1437-1443 · IF 0.524

Liquefaction of Banana Pseudo-stem and Preparation of Polyurethane Adhesive from Liquefied Products

Zhou Wei,Fu Wenxing,Zhang Yucang

Banana pseudo-stem was liquefied in the mixture of polyhydric alcohols of polyethylene glycol (PEG400) and glycerol. Hydroxyl value of liquefied products ranged from 294.8 to 370.2 mg KOH/g and \({\bar M_n}\) was about 430. Liquefied products (LBPP) could be used as raw materials for polyurethane by reacting with 4, 4’-diphenylmethane diisocyanate (4, 4’-MDI) and PEG400 to synthesize liquefied product-based polyurethane (LBPP-PU) adhesive. To analyze in depth the creation of urethane linkage among LBPP, PEG400 and 4, 4’-MDI, factors which had effects on the residue content were all investigated. They were characterized by FT-IR and TG. The shear strength of LBPP-PU adhesive was improved when decreasing the percentage of the substitution of PEG400 by LBPP. The adhesive strength was obtained from T-peel of aspen/polyurethane adhesive joints, and the maximum lap shear strength (4.40 MPa) was obtained when 16.70% of LBPP was added to the LBPP & PEG400 system.

CAS / MDL: 101-68-8
研究领域: 材料科学 · 生物化学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2019 · IF 4.784

Mesenchymal stem cells-curcumin loaded chitosan nanoparticles hybrid vectors for tumor-tropic therapy

Menglu Xu,Sajid Asghar,Shuang Dai,Yajing Wang,Shanshan Feng,Liang Jin,Feng Shao,Yanyu Xiao

The combination of controlled release technology and targeted drug delivery has become a promising strategy for cancer therapy. In this study, cell-nanoparticle hybrid vector was constructed using mesenchymal stem cells as the targeting cellular carrier and biotinylated chitosan polymer nanoparticles as the drug depot. Drug-loaded nanoparticles (hydrodynamic size =377.0 ± 14.6 nm and zeta potential = 9.6 ± 1.9 mV) were prepared by encapsulating hydrophobic model drug curcumin into biotinylated chitosan polymer. The biotin-modified nanoparticles were anchored on biotinylated mesenchymal stem cells surface by biotin-avidin binding, achieving an upload of 54.73 ± 3.95 pg/cell. The anchorage of nanoparticles on mesenchymal stem cells had no effect on their viability and homing property. Biotin-avidin binding lasted over 48 h, which could be sufficient for cell-directed tumor-tropic delivery. The in vitro and in vivo anti-tumor results advocate that cell-nanoparticle hybrid vector could prove beneficial in pulmonary melanoma metastasis therapy.

研究领域: 生物医学工程 · 药学 · 肿瘤学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ANNALS OF PLASTIC SURGERY · 2020 ·Vol. 84 ·期 3 ·328 · IF 1.354

Tetramethylpyrazine/Ligustrazine Can Improve the Survival Rate of Adipose-Derived Stem Cell Transplantation

Zhou Jinghe,Zhang Jufang,Wu Lihong,Zhu Fei,Xu Huifang

Background We aimed to study the effect of tetramethylpyrazine/ligustrazine ( TMP ) on the survival rate of adipose-derived stem cell (ADSC) transplantation . Methods Human ADSCs were cultured and subcultured. Detection of cell growth was performed using CCK8 kit. A total of 12 BALB/c nude mice including 4 groups (group 1: ADSC–hyaluronic acid [HA] + phosphate-buffered saline [PBS]; group 2: ADSC-HA + TMP injection; group 3: ADSC-HA + TMP soaking; group 4: ADSC-HA + TMP injection + TMP soaking) were used for the animal experiments. Furthermore, hematoxylin-eosin staining and oil red O staining were conducted for the frozen section from the animal tissues. Besides, RNA was extracted from the samples, and reverse transcriptase–polymerase chain reaction experiment was performed. At last, samples were detected using transmission electron microscope. Results Tetramethylpyrazine/ligustrazine resulted in significant increase for cell proliferation on the seventh day. It was easier to promote the growth of adipose cell after injection and soaking of TMP . Hematoxylin-eosin staining and oil red O stain showed that injection and soaking of TMP could significantly increase the size of fat. The relative expression of peroxisome proliferator–activated receptor γ, CCAAT/enhancer-binding protein α, and Alu in group 4 was significantly higher than that in other groups. Conclusions Tetramethylpyrazine/ligustrazine can improve the survival rate of ADSC transplantation . The possible mechanisms of it may be that TMP induces the expression of transcription factor associated with fat formation including peroxisome proliferator–activated receptor γ, CCAAT/enhancer-binding protein α, and Alu and then promotes the growth of adipose cell.

CAS / MDL: 301-04-2
研究领域: 干细胞研究 · 分子生物学 · 药理学
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ADVANCED MATERIALS · 2023 ·Vol. 35 ·期 19 ·2210637 · IF 29.4

Assessing Biomaterial-Induced Stem Cell Lineage Fate by Machine Learning-Based Artificial Intelligence

Yingying Zhou,Xianfeng Ping,Yusi Guo,Boon Chin Heng,Yijun Wang,Yanze Meng,Shengjie Jiang,Yan Wei,Binbin Lai,Xuehui Zhang,Xuliang Deng

Current functional assessment of biomaterial-induced stem cell lineage fate in vitro mainly relies on biomarker-dependent methods with limited accuracy and efficiency. Here a “Mesenchymal stem cell Differentiation Prediction (MeD-P)” framework for biomaterial-induced cell lineage fate prediction is reported. MeD-P contains a cell-type-specific gene expression profile as a reference by integrating public RNA-seq data related to tri-lineage differentiation (osteogenesis, chondrogenesis, and adipogenesis) of human mesenchymal stem cells (hMSCs) and a predictive model for classifying hMSCs differentiation lineages using the k-nearest neighbors (kNN) strategy. It is shown that MeD-P exhibits an overall accuracy of 90.63% on testing datasets, which is significantly higher than the model constructed based on canonical marker genes (80.21%). Moreover, evaluations of multiple biomaterials show that MeD-P provides accurate prediction of lineage fate on different types of biomaterials as early as the first week of hMSCs culture. In summary, it is demonstrated that MeD-P is an efficient and accurate strategy for stem cell lineage fate prediction and preliminary biomaterial functional evaluation.

CAS / MDL: 13033-84-6 121-44-8
研究领域: 干细胞生物学 · 生物医学工程 · 机器学习 · 人工智能 · 生物材料科学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2022 · IF 5.999

Hyaluronic acid mediated Fe3O4 nanocubes reversing the EMT through targeted cancer stem cell

Yuhui Wang,Shilong Ma,Xuanyu Liu,Yan Wei,Haofeng Xu,Ziwei Liang,Yinchun Hu,Xiaojie Lian,Di Huang

Hepatocellular carcinoma (HCC) is one of the deadliest tumors in the world with a high rate of recurrence and metastasis. Therefore, the most pressing issue today is the development of new drugs, diagnostic and therapeutic approaches for effective cancer treatment. Cancer stem cells (CSCs) play a pivotal role in tumor recurrence, tumor resistance, and tumor metastasis, which provides a new perspective on the development of liver cancer. In the study, a high-temperature thermal breakdown approach was used to create composite magnetic nanocubes modified by polyethyleneimine (PEI) and hyaluronic acid (HA). The Fe 3 O 4 nanocubes can recognize HCC stem cells via receptor−ligand binding of HA and CD44 (HA receptor). While loading a small molecule LDN193189 inhibited the expression of stemness-related genes OCT4 and Nanog . More crucially, the Fe 3 O 4 nanocubes significantly suppressed HCC cell proliferation and migration by regulating the expression of epithelial-mesenchymal transition (EMT) process markers E-cadherin, Vimentin , and N-cadherin. Dual targeting using magnetic and receptor-mediated targeting improved the uptake of the drug delivery system. Our findings imply that the medication delivery method might be a potential therapeutic strategy for HCC.

研究领域: 癌症生物学 · 纳米技术 · 药学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Nanoscale · 2014 ·Vol. 6 ·期 15 ·9025-9033 · IF 6.739

Functional investigations on embryonic stem cells labeled with clinically translatable iron oxide nanoparticles

Jing Liu,Liqin Wang,Jianbo Cao,Yue Huang,Yu Lin,Xiaoyun Wu,Zhiyong Wang,Fan Zhang,Xiuqin Xu,Gang Liu

Stem cell based therapies offer significant potential in the field of regenerative medicine. The development of superparamagnetic iron oxide (SPIO) nanoparticle labeling and magnetic resonance imaging (MRI) have been increasingly used to track the transplanted cells, enabling in vivo determination of cell fate. However, the impact of SPIO-labeling on the cell phenotype and differentiation capacity of embryonic stem cells (ESCs) remains unclear. In this study, we wrapped SPIO nanoparticles with stearic acid grafted PEI600, termed as Stearic–LWPEI–SPIO, to generate efficient and non-toxic ESC labeling tools. Our results showed that efficient labeling of ESCs at an optimized low dosage of Stearic–LWPEI–SPIO nanoparticles did not alter the differentiation and self-renewal properties of ESCs. The localization of the transplanted ESCs observed by MRI correlated well with histological studies. These findings demonstrate that Stearic–LWPEI–SPIO nanoparticles have potential to be clinically translatable MRI probes and may enable non-invasive in vivo tracking of ESCs in experimental and clinical settings during cell-based therapies.

研究领域: 再生医学 · 纳米技术 · 细胞生物学 · 分子影像
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