ARCHIVES OF ORAL BIOLOGY
·
2021
·
IF 2.635
Yujia Cui,Mingru Bai,Daimo Guo,Yueyi Yang,Haoran Chen,Jianxun Sun,Jing Xie,Xuedong Zhou
Objective Insulin-like growth factor 1 (IGF1) is one of the vital factors in regenerative endodontics . Previous studies have focused on the role of IGF1 in the mineralization of dental tissues. However, the role of IGF1 in the neural differentiation of dental stem cells was little discussed. Design IGF1 was overexpressed in human stem cells from the apical papilla (hSCAPs) by lentivirus and knocked down in hSCAPs by small interfering RNA . The neural differentiation level of hSCAPs was investigated histologically by HE staining and Nissl staining after neural induction for 3 days. The expression of proteins was examined by western blot and immunofluorescence. Results IGF1 promoted neural differentiation of hSCAPs, more cell processes and Nissl-positive body stained cells. IGF1 overexpression could both promote glial differentiation in hSCAPs, characterized by the increase of S100β and GFAP proteins, and neuronal differentiation , characterized by the increase of βIII-tubulin and functional GAD67/vGLUT1 proteins. Conversely, IGF1 knockdown suppressed both glial and neuronal differentiation. IGF1 activated AKT to regulate the early neural differentiation of hSCAPs. Conclusions The results indicate IGF1 could promote neural differentiation of hSCAPs by activating AKT signaling and provide a cue for the candidate of induced neural seeding cells in regenerative endodontics.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 10
·期 3
·808-818
·
IF 6.843
Na Tang,Xueyi Wang,Jin Zhu,Kang Sun,Shiting Li,Ke Tao
It is crucial and clinically relevant to clarify the homing efficiency and retention of stem cells in different implanting strategies of cell therapy for various injuries. However, the need for a tool for investigating the mechanisms is still unmet. We herein introduce multi-modal BaGdF5:Yb,Tm nanoparticles as a nanoprobe to label adipose-derived stem cells (ADSCs) and detect the homing behavior with a micro-computed tomography (micro-CT) imaging technique. The migration of cells injected locally or intravenously, with or without a chemokine, CXCL 12, was compared. A higher homing efficiency of ADSCs was observed in both intravenously injected groups, in contrast to the low efficiency of cell retention in local implantation. Meanwhile, CXCL 12 promoted the homing of ADSCs, especially in the intravenous route. Nonetheless, the administration of CXCL 12 showed its therapeutic efficacy, whereas intravenous injection of ADSCs almost did not. Our work provided a tool for in vivo imaging of the behavior of implanted cells in preclinical studies of cell therapy, and more importantly, implied that the parameters for implanting stem cells in clinical operation should be carefully considered.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biofabrication
·
2021
·Vol. 14
·期 1
·015012
·
IF 10.02
Jianwei Chen,Duchao Zhou,Zhenguo Nie,Liang Lu,Zhidong Lin,Dezhi Zhou,Yi Zhang,Xiaoyan Long,Siyang Fan,Tao Xu
Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are promising candidates for regenerative medicine; however, the lack of scalable methods for high quantity EV production limits their application. In addition, signature EV-derived proteins shared in 3D environments and 2D surfaces, remain mostly unknown. Herein, we present a platform combining MSC microfiber culture with ultracentrifugation purification for high EV yield. Within this platform, a high quantity MSC solution (∼3 × 108 total cells) is encapsulated in a meter-long hollow hydrogel-microfiber via coaxial bioprinting technology. In this 3D core–shell microfiber environment, MSCs express higher levels of stemness markers (Oct4, Nanog, Sox2) than in 2D culture, and maintain their differentiation capacity. Moreover, this platform enriches particles by ∼1009-fold compared to conventional 2D culture, while preserving their pro-angiogenic properties. Liquid chromatography-mass spectrometry characterization results demonstrate that EVs derived from our platform and conventional 2D culturing have unique protein profiles with 3D-EVs having a greater variety of proteins (1023 vs 605), however, they also share certain proteins (536) and signature MSC-EV proteins (10). This platform, therefore, provides a new tool for EV production using microfibers in one culture dish, thereby reducing space, labor, time, and cost.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2021
·Vol. 12
·期 1
·1-14
·
IF 6.832
Yang Zheng,Yang Yang,Xu Yichi,Jiang Weiqian,Shao Yan,Xing Jiahua,Chen Youbai,Han Yan
Background Efficient and stable delivery of neurotrophic factors (NTFs) is crucial to provide suitable microenvironment for peripheral nerve regeneration. Neurotrophin-3 (NT-3) is an important NTF during peripheral nerve regeneration which is scarce in the first few weeks of nerve defect. Exosomes are nanovesicles and have been served as promising candidate for biocarrier. In this work, NT-3 mRNA was encapsulated in adipose-derived stem cell (ADSC)-derived exosomes (Exo NT-3 ). These engineered exosomes were applied as NT-3 mRNA carrier and then were loaded in nerve guidance conduit (Exo NT-3 -NGC) to bridge rat sciatic nerve defect. Method NT-3 mRNA was encapsulated in exosomes by forcedly expression of NT-3 mRNA in the donor ADSCs. Exo NT-3 were co-cultured with SCs in vitro; after 24 h of culture, the efficiency of NT-3 mRNA delivery was evaluated by qPCR, western blotting and ELISA. Then, Exo NT-3 were loaded in alginate hydrogel to construct the nerve guidance conduits (Exo NT-3 -NGC). Exo NT-3 -NGC were implanted in vivo to reconstruct 10 mm rat sciatic nerve defect. The expression of NT-3 was measured 2 weeks after the implantation operation. The sciatic nerve functional index (SFI) was examined at 2 and 8 weeks after the operation. Moreover, the therapeutic effect of Exo NT-3 -NGC was also evaluated by morphology assay, immunofluorescence staining of regenerated nerves, function evaluation of gastrocnemius muscles after 8 weeks of implantation. Results The engineered exosomes could deliver NT-3 mRNA to the recipient cells efficiently and translated into functional protein. The constructed NGC could realize stable release of exosomes at least for 2 weeks. After NGC implantation in vivo, Exo NT-3 -NGC group significantly promote nerve regeneration and improve the function recovery of gastrocnemius muscles compared with control exosomes (Exo empty -NGC) group. Conclusion In this work, NGC was constructed to allow exosome-mediated NT-3 mRNA delivery. After Exo NT-3 -NGC implantation in vivo, the level of NT-3 could restore which enhance the nerve regeneration. Our study provide a potential approach to improve nerve regeneration.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2021
·Vol. 13
·期 8
·1205
·
IF 6.321
Shuang Ba,Mingxi Qiao,Li Jia,Jiulong Zhang,Xiuli Zhao,Haiyang Hu,Dawei Chen
Cancer stem-like cells (CSLCs) have been considered to be one of the main problems in tumor treatment owing to high tumorigenicity and chemotherapy resistance. In this study, we synthesized a novel mitochondria-target derivate, triphentlphosphonium-resveratrol (TPP-Res), and simultaneously encapsulated it with doxorubicin (Dox) in pH-sensitive liposomes (PSL (Dox/TPP-Res)), to reverse chemotherapeutic resistance of CSLCs. PSL (Dox/TPP-Res) was approximately 165 nm in size with high encapsulation efficiency for both Dox and TPP-Res. Cytotoxicity assay showed that the optimal synergistic effect was the drug ratio of 1:1 for TPP-Res and Dox. Cellular uptake and intracellular trafficking assay indicated that PSL (Dox/TPP-Res) could release drugs in acidic endosomes, followed by mitochondrial targeting of TPP-Res and nucleus transports for Dox. The mechanisms for reversing the resistance in CSLCs were mainly attributed to a synergistic effect for reduction of mitochondrial membrane potential, activation of caspase cascade reaction, reduction of ATP level and suppression of the Wnt/β-catenin pathway. Further, in vivo assay results demonstrated that the constructed liposomes could efficiently accumulate in the tumor region and possess excellent antineoplastic activity in an orthotopic xenograft tumor model with no evident systemic toxicity. The above experimental results determined that PSL (Dox/TPP-Res) provides a new method for the treatment of heterogenecity tumors.Keywords:TPP conjugate;hierarchical targetability;cancer stem-like cells
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Zhuo Liang,Li Yang,Yonggang Lv
Gene therapy based on non-viral vector has been used to promote the repair of bone damage. However, low transfection efficiency and uncontrollable expression greatly hinder its clinical translation. Exosomes (Exos) have been extensively studied as a promising non-viral delivery carrier recently, while its delivery efficiency for large nucleic acids is low. Here, a novel gene vector was developed by layer-by-layer self-assembly method using polyethyleneimine (PEI) and Exos derived from mesenchymal stem cells (MSCs) to deliver large plasmids efficiently. Moreover, a hypoxia-specific expression plasmid was constructed by combining hypoxia promoter RTP801 and microRNA 877 (miR877) sponge. Experimental results showed that the gene delivery vector based on Exos exhibited high transfection efficiency and low cytotoxicity to MSCs. The hypoxia-specific expression plasmid significantly increased bone morphogenetic protein 2 ( BMP2 ) expression in hypoxic condition and promoted neoangiogenesis. This study may provide a novel method to improve the repair efficiency in bone tissue engineering.
✓ 已验证
产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2020
·
IF 4.152
Yuanning Lyu,Jinghui Xie,Yang Liu,Meng Xiao,Yuan Li,Jianhai Yang,Jun Yang,Wenguang Liu
Conventional strategies of stem cell injection in treating myocardial infarction (MI) remain a challenge because of low retention rate and insufficient secretion of exogenous cytokines for efficiently improving the microenvironment in the infarcted myocardium, thus hampering the therapeutic effect. Herein, poly(lactic-co-glycolic acid) (PLGA) microparticles modified with human VE-cad-Fc fusion protein are fabricated and integrated with human mesenchymal stem cells (hMSCs) to construct functionalized MSC aggregates (FMAs). This fusion protein can effectively promote the paracrine activity of MSCs. The FMA is encapsulated with an injectable hyaluronic acid (HA)-based hydrogel, which is prepared by Schiff base reaction between oxidized HA (OHA) and hydrazided HA (HHA). The OHA@HHA hydrogel loading FMA is injected into the infarcted myocardium of rats, thereby efficiently improving the MI microenvironment in terms of decreased expressions of inflammatory cytokines and upregulated secretion of angiogenic factors compared to the plain hydrogel only and hydrogel encapsulating MSCs. The results of both echocardiography and histological analyses demonstrate the efficient reconstruction of cardiac function and structure and revascularization in the infarct myocardium. The delivery of functionalized stem cell aggregates with an injectable hydrogel offers a promising strategy for treating myocardial infarction and may be expanded to other tissue repair and reconstruction.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
·
2020
·Vol. 319
·期 6
·E961
·
IF 3.469
Ruixi Luo,Linzhao Li,Xiaohong Liu,Yujia Yuan,Wuzheng Zhu,Lan Li,Jingping Liu,Yanrong Lu,Jingqiu Cheng,Younan Chen
Download figureDownload PowerPoint High levels of plasma free fatty acids (FFAs) lead to endothelial dysfunction (ED), which is involved in the pathogenesis of metabolic syndrome, diabetes, and atherosclerosis. Endoplasmic reticulum (ER) stress and endothelial-to-mesenchymal transition (EndMT) are demonstrated to be mechanistically related to endothelial dysfunction. Mesenchymal stem cells (MSCs) have exhibited an extraordinary cytoprotective effect on cellular lipotoxicity and vasculopathy. However, the underlying mechanisms have not been clearly defined. In the present study, we investigated whether MSCs could ameliorate palmitic acid (PA)-induced endothelial lipotoxicity by reducing ER stress and EndMT. We observed that MSC cocultures substantially alleviated PA-induced lipotoxicity in human umbilical vein endothelial cells (HUVECs). MSCs were able to restore the cell viability, increase tubule formation and migration ability, and decrease inflammation response and lipid deposition. Furthermore, PA caused endothelial-to-mesenchymal transition in HUVECs, which was abrogated by MSCs possibly through inhibiting ER stress. In addition, PA stimulated MSCs to secrete more stanniocalcin-1 (STC-1). Knocking down of STC-1 in MSCs attenuated their effects on PA-induced lipotoxicity in HUVECs. In vivo, MSC transplantation alleviated dyslipidemia and endothelial dysfunction in high-fat diet-fed Sprague–Dawley rats. MSC-treated rats showed reduced expressions of ER stress-related genes in aortas and suppressed expressions of EndMT-related proteins in rat aortic endothelial cells. Overall, our findings indicated that MSCs were able to attenuate endothelial lipotoxicity through inhibiting ER stress and EndMT, in which STC-1 secreted from MSCs may play a critical role.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Neural Regeneration Research
·
2020
·
IF 3.171
Chao-Qun Lin,Lu-Kui Chen
Previous research found that cerebral dopamine neurotrophic factor (CDNF) has a protective effect on brain dopaminergic neurons, and CDNF is regarded as a promising therapeutic agent for neurodegenerative diseases. However, the effects of CDNF on the proliferation, differentiation, and apoptosis of neural stem cells (NSCs), which are very sensitive to hypoxic environments, remain unknown. In this study, NSCs were extracted from the hippocampi of fetal rats and cultured with different concentrations of CDNF. The results showed that 200 nM CDNF was the optimal concentration for significantly increasing the viability of NSCs under non-hypoxic environmental conditions. Then, the cells were cultured with 200 nM CDNF under the hypoxic conditions of 90% N 2 , 5% CO 2 , and 5% air for 6 hours. The results showed that CDNF significantly improved the viability of hypoxic NSCs and reduced apoptosis among hypoxic NSCs. The detection of markers showed that CDNF increased the differentiation of hypoxic NSCs into neurons and astrocytes. CDNF also reduced the expression level of Lin28 protein and increased the expression of Let-7 mRNA in NSCs, under hypoxic conditions. In conclusion, we determined that CDNF was able to reverse the adverse proliferation, differentiation, and apoptosis effects that normally affect NSCs in a hypoxic environment. Furthermore, the Lin28/Let-7 pathway may be involved in this regulated function of CDNF. The present study was approved by the Laboratory Animal Centre of Southeast University, China (approval No. 20180924006) on September 24, 2018.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Rong Yang,Xiaoxue Wang,Shuai Liu,Wenjie Zhang,Penghui Wang,Xin Liu,Yanhan Ren,Xiaoyan Tan,Bo Chi
While peptide-directed scaffolds now serve as well-established platforms for biomimetic three-dimensional (3D) extracellular matrices (ECM), challenges still remain for chondrogenesis through direct mediation of stem cells. Here, biocompatible poly (γ-glutamic acid) (γ-PGA) hydrogels with robust mechanical properties were developed based on methacrylate-γ-PGA (γ-PGA-GMA) and cysteamine functionalized γ-PGA (γ-PGA-SH) for cartilage regeneration. The γ-PGA hydrogels demonstrated good self-crosslinking property as well as tunability through conjugation between active thiol groups of γ-PGA-SH and methacrylate moieties of γ-PGA-GMA. The mechanical property, porous structure, swelling, and degradation process of the hydrogels could be controlled by adjusting modified γ-PGA polymers component. The rheological behavior and compression test of γ-PGA hydrogels illustrated a wide processing range in addition to superb mechanical properties. These γ-PGA hydrogels showed excellent elasticity as well as toughness, withstanding more than 70% of mechanical strain. Meanwhile, the stress modulus of γ-PGA hydrogels could be up to 749 kPa. We also studied γ-PGA hydrogels as scaffolds for the 3D culture and chondrogenesis differentiation of rabbit bone marrow-derived mesenchymal stem cells (BMSCs) in vitro . In a rabbit auricular cartilage defect model, BMSCs-laden hydrogel effectively promoted chondrogenesis. Based on these findings, biomimetic γ-PGA-based hydrogels hold promising application as favorable scaffold biomaterials for cartilage tissue regeneration.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Jing Hong,Zhanchi Zhu,Leisha Cui,Zhaojun Wang,Ying Hao,Xiaopeng Tian,Guosheng Cheng
Hematopoietic stem cell (HSC) expansion offers a key strategy to address the source limitation and donor shortages of HSCs for the treatment of various blood disorders. Specific remodeling of the complex bone marrow microenvironment that contributes to efficient in vitro expansion of HSCs remains challenging. Here, inspired by the regions with different stiffness levels in the bone marrow niche, a three dimensional (3D) bone marrow-mimicking composite scaffold created based on gelatin–hyaluronic acid (Gel–HA) hydrogels and graphene foams (GFs) was engineered to support the in vitro expansion of HSCs. The composite scaffold was prepared by forming a photo-cross-linked Gel–HA hydrogel surrounding the GF. The “soft” Gel–HA hydrogel and “stiff” GF replicate the structure and stiffness of the vascular niche and endosteal niche in the bone marrow, respectively. Furthermore, HSCs cultured in the Gel–HA/GF scaffold proliferated well and retained the CD34+CD38− immunophenotype and pluripotency, suggesting that the Gel–HA/GF composite scaffold supported the in vitro expansion of HSCs, maintaining the primitive phenotype and the ability to differentiate into functional blood cells. Thus, the hydrogel/graphene composite scaffold offers a means of facilitating HSC expansion through structurally and mechanically mimicking bone marrow niches, demonstrating great promise for HSC transplantation.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2017
·Vol. 14
·期 2
·1795-1801
·
IF 1.261
Qiang Zhang,Guangdong Cheng,Hongbin Qiu,Yuexin Wang,Jingtao Wang,Hui Xu,Tao Zhang,Lixin Liu,Ye Tao,Zhongjuan Ren
Prostate stem cell antigen (PSCA) is expressed in the majority of prostate cancer cases and may be a potential therapeutic target in the treatment of prostate cancer. The present study evaluated the cytotoxicity of three flavonoids (genistein, luteolin and quercetin) towards DU145 prostate cancer cells, and investigated the effect of these flavonoids on PSCA expression. The results demonstrated that genistein, luteolin and quercetin inhibited the growth of DU145 cells in a dose-dependent manner (P<0.05) and induced morphological changes characteristic of apoptosis in DU145 cells. Flow cytometry analysis also indicated that the flavonoids induced S phase cycle arrest in DU145 cells. Notably, it was observed that expression of PSCA was inhibited at the mRNA (P<0.05) and protein levels in DU145 cells following flavonoid treatment compared with the control. These results suggest that flavonoids may be potential therapeutic agents in the treatment and prevention of prostate cancer.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）