Stem Cells International
·
2021
·
IF 5.443
Yuxin Zhao,Bobo Cai,Weijun Zhu,Jue Shi,Yu Wang,Misi Si
Mesenchymal stem cells (MSCs) have been considered to be a future treatment option for periodontitis due to their excellent regenerative capability. However, it is still a challenge to protect MSCs’ biological properties from multiple bacterial toxins in local inflammatory environment. The present study is aimed at investigating the treatment effect of interleukin-1 receptor antagonist (IL-1ra) on cell proliferation, migration, and osteogenic differentiation of gingival-derived mesenchymal stem cells (GMSCs) under an inflammatory microenvironment induced by Porphyromonas gingivalis lipopolysaccharides (P. gingivalis-LPS). GMSCs derived from Sprague-Dawley (SD) rats’ free gingival tissues were treated with P. gingivalis-LPS (10 μg/mL) to create in vitro inflammatory environment. Different concentrations of IL-1ra (0.01-1 μg/mL) were used to antagonize the negative effect of LPS. Cell behaviors including proliferation, cloning formation unit (CFU), cell migration, osteogenic differentiation, mineral deposition, and cytokine production were assessed to investigate the protection effect of IL-1ra on GMSCs under inflammation. The toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway activated by LPS was evaluated by real-time quantitative polymerase chain reaction (RT-PCR) and western blot. In response to P. gingivalis-LPS treatment, cell numbers, cloning formation rate, cell migration rate, proinflammatory cytokine production, and osteogenic differentiation-associated protein/mRNA expressions as well as mineralized nodules were suppressed in a time-dependent manner. These negative effects were effectively attenuated by IL-1ra administration in a time- and dose-dependent manner. In addition, mRNA expressions of TLR4 and IkBα decreased dramatically when IL-1ra was added into LPS-induced medium. IL-1ra also reversed the LPS-induced TLR4/NF-κB activation as indicated by western blot. The present study revealed that IL-1ra decreased inflammatory cytokine production in a supernatant, so as to protect GMSCs’ osteogenesis capacity and other biological properties under P. gingivalis-LPS-induced inflammatory environment. This might be explained by IL-1ra downregulating TLR4-mediated NF-κB signaling pathway activation.
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Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 15
·3016-3027
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IF 5.344
Qian Wu,Kaipeng Wang,Xichao Wang,Guohai Liang,Jinming Li
Controlling and detecting cell differentiation in human mesenchymal stem cells (hMSCs) for regenerative medicine remain challenging at present. Here, we developed multifunctional gold nanoparticles (AuNPs) to control and detect osteogenic differentiation in human mesenchymal stem cells (hMSCs) in real-time. The polyethyleneimine (PEI) capped AuNPs (Au-PEI) were synthesized first and were then conjugated with a matrix metalloproteinase 13 (MMP13)-sensitive peptide-FITC group (EGPLGVRGKG-FITC) to obtain multifunctional AuNPs (AuNP-PEI-peptide-FITC). AuNP-PEI-peptide-FITC could bind siRNA with PEI by electrostatic interactions to form the AuNP-PEI-peptide-FITC/siRNA nanocomplexes, allowing efficient siRNA delivery in hMSCs. The adipogenic-related gene peroxisome proliferator-activated receptor γ (PPARγ) was targeted for silencing by the AuNP-PEI-peptide-FITC/siRNA nanocomplexes to control osteogenic differentiation in hMSCs. After demonstrating that the AuNP nanocomplexes could control cell differentiation, the versatility of this tool was illustrated by showing that it can be used as a nanoprobe for real time detection of the osteogenic differentiation of hMSCs. This was done by measuring the activity of the MMP13 enzyme (produced during osteogenic differentiation) through the recovery of FITC fluorescence. This multifunctional AuNP showed a robust new methodology for controlling cell fate and simultaneously detecting cell differentiation in real-time for hMSCs, which is promising for multiple applications in regenerative medicine.
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Biomedical Materials
·
2020
·Vol. 15
·期 3
·035020
·
IF 3.174
Junni Zhang,Tian Cheng,Yihao Chen,Feng Gao,Fangxia Guan,Minghao Yao
Spinal cord injury is a devastating trauma with high mortality and disability, for which there is no effective treatment. Stem cell-based tissue engineering has been reported to promote functional neural recovery. At present, building a neural scaffold with excellent biocompatibility for cells and tissues is still challenging. In this study, a new thermosensitive composite hydrogel based on chitosan, hydroxyethyl cellulose, collagen and β-phosphoglycerate (CS-HEC-Col/GP hydrogel) is developed to encapsulate murine bone marrow-derived mesenchymal stem cells (BMSCs) to improve therapeutic efficacy in spinal cord injured mice. This composite hydrogel possesses a good cytocompatibility to mouse BMSCs by live/dead staining, minimized inflammatory reaction in vivo by hematoxylin and eosin staining and suitable rheological behavior similar to neural tissue, ranging from 100 to 1000 Pa. Furthermore, the data from animal experiments indicated that BMSC-loaded CS-HEC-Col/GP hydrogel could enhance the survival or proliferation of endogenous nerve cells, probably by secreting neurotrophic factors and inhibiting apoptosis, and thereby promote the recovery of motor function in the hindlimbs of a murine spinal cord injury model.
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Materials Today Bio
·
2022
·
IF 10.761
Wentao Zhang,Tianze Sun,Jing Zhang,Xiantong Hu,Ming Yang,Liwei Han,Gang Xu,Yantao Zhao,Zhonghai Li
The presence of periosteum can greatly affect the repair of a bone fracture. An artificial periosteum imitates the biological function of natural periosteum, which is capable of protecting and maintaining bone tissue structure and promoting bone repair. In our artificial periosteum, biocompatible methacrylate gelatin was used to provide the mechanical support of the membrane, E7 peptide added bioactivity, and Wharton's jelly provided the biological activity support of the membrane, resulting in a hydrogel membrane (G-E-W) for the chemotactic recruitment of bone marrow mesenchymal stem cells (BMSCs) and promoting cell proliferation and osteogenic differentiation. In an in vitro experiment, the G-E-W membrane recruited BMSCs and promoted cell proliferation and osteogenic differentiation. After 4 weeks and 8 weeks of implantation in a rat skull defect, the group implanted with a G-E-W membrane was superior to the blank control group and single-component membrane group in both quantity and quality of new bone. The artificial G-E-W membrane recruits BMSC chemotaxis and promotes cell proliferation and osteogenic differentiation, thereby effectively improving the repair efficiency of fractures and bone defects.
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TISSUE & CELL
·
2023
·
IF 2.6
Yao Duan,Chanyuan Jin,Yuwei Wu,Yan Chen,Minjuan Zhang,Jun Qian,Ting Shuai,Jian Li,Huimin Chen,Dan Li
Periodontitis represents a severe inflammatory illness in tooth supporting tissue. It has been supported that cAMP response element binding protein 1 (CREB1), a common transcription factor, extensively participates in osteogenic differentiation. Here, the current study was to look into the impacts of CREB1 on the process of periodontitis and its possible action mechanism. After human periodontal ligament stem cells (PDLSCs) were challenged with zoledronic acid (ZA), CREB1 expression was examined with RT-qPCR and western blotting . CCK-8 assay appraised cell activity. Following CREB1 elevation or/and vascular endothelial growth factor (VEGF) silencing in ZA-treated PDLSCs, CCK-8 and TUNEL assays separately estimated cell viability and apoptosis. Western blotting tested the expression of apoptosis- and osteogenic differentiation-associated proteins. ALP staining measured PDLSCs osteogenic ability and ARS staining estimated mineralized nodule formation. JASPAR predicted the potential binding of CREB1 with VEGF promoter, which was then testified by ChIP and luciferase reporter assays. RT-qPCR and western blotting tested VEGF expression. CREB1 expression was declined in ZA-exposed PDLSCs and CREB1 elevation exacerbated the viability and osteogenic differentiation while obstructed the apoptosis of PDLSCs. Additionally, CREB1 bond to VEGF promoter and transcriptionally activated VEGF expression. Further, VEGF absence partially stimulated the apoptosis while suppressed the osteogenic differentiation of CREB1-overexpressing PDLSCs treated by ZA. To be concluded, CREB1 might activate VEGF transcription to obstruct the apoptosis while contribute to the osteogenic differentiation of ZA-treated PDLSCs.
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JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Tianli Yang,Feng Zhao,Jun Zhao,Jian Geng,Cheng Shao,Jingyu Liu,Fei Sheng,Liuhua Zhou,Hua Xu,Ruipeng Jia
Adipose-derived mesenchymal stem cell-derived small extracellular vesicles (Ad-MSC-sEVs/AMEs) combined with scaffold materials are used in tissue-engineered bladders; however, the lack of retention leads to limited distribution of AMEs in the scaffold areas and low bioavailability of AMEs after bladder reconstruction. To improve retention of AMEs, we developed a novel strategy that modifies the surface charge of the bladder acellular matrix (BAM) via oxidative self-polymerization of dopamine-reducing graphene oxide (GO) and AMEs using ε-polylysine-polyethylene-distearyl phosphatidylethanolamine (PPD). We evaluated two BAM surface modification methods and evaluated the biocompatibility of materials and PPD and electrostatic adherence effects between PPD-modified AMEs and rGO-PDA/BAM in vivo and in vitro. Surface modification increased retention of AMEs, enhanced regeneration of bladder structures, and increased electrical conductivity of rGO-PDA/BAM, thereby improving bladder function recovery. RNA-sequencing revealed 543 miRNAs in human AMEs and 514 miRNAs in rat AMEs. A Venn diagram was used to show target genes of miRNA with the highest proportion predicted by the four databases; related biological processes and pathways were predicted by KEGG and GO analyses. We report a strategy for improving bioavailability of AMEs for bladder reconstruction and reveal that enriched miR-21-5p targets PIK3R1 and activates the PI3K/Akt pathway to promote cell proliferation and migration.
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Pharmaceutics
·
2023
·Vol. 15
·期 10
·2503
·
IF 5.4
Yuchen Zhou,Jie Liu,Peng Xue,Jianjun Zhang
GSK2606414 is a new, effective, highly selective PERK inhibitor with adenosine-triphosphate-competitive characteristics. It can inhibit endoplasmic reticulum stress and has the possibility of treating periodontitis. However, owing to its strong hydrophobicity and side effects, highly efficient pharmaceutical formulations are urgently needed to improve the bioavailability and therapeutic efficacy of GSK2606414 in the treatment of periodontitis. Herein, a novel local GSK2606414 delivery system was developed by synthesizing GSK2606414 nanoparticles (NanoGSK) and further loading NanoGSK into a collagenase-responsive hydrogel. The drug release results showed that the drug-loaded hydrogels had outstanding enzymatic responsive drug release profiles under the local microenvironment of periodontitis. Furthermore, in vitro studies showed that the drug-loaded hydrogel exhibited good cellular uptake and did not affect the growth and proliferation of normal cells, while the drug-loaded hydrogel significantly improved the osteogenic differentiation of inflammatory cells. In the evaluations of periodontal tissue repair, the drug-loaded hydrogels showed a great effect on inflammation inhibition, as well as alveolar bone regeneration. Therefore, this work introduces a promising strategy for the clinical treatment of periodontitis.Keywords:GSK2606414;nanoparticles;PERK;hydrogel;periodontitis
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Journal of Biological Engineering
·
2023
·Vol. 17
·期 1
·1-20
·
IF 5.6
Liu Tiemei,Zhang Qiang,Li Hongru,Cui Xiaoqian,Qi Zhiping,Yang Xiaoyu
Background Spinal cord injury (SCI) is a serious injury with high mortality and disability rates, and there is no effective treatment at present. It has been reported that some treatments, such as drug intervention and stem cell transplantation have positive effects in promoting neurological recovery. Although those treatments are effective for nerve regeneration, many drawbacks, such as low stem cell survival rates and side effects caused by systemic medication, have limited their development. In recent years, injectable hydrogel materials have been widely used in tissue engineering due to their good biocompatibility, biodegradability, controllable properties, and low invasiveness. The treatment strategy of injectable hydrogels combined with stem cells or drugs has made some progress in SCI repair, showing the potential to overcome the drawbacks of traditional drugs and stem cell therapy.
Methods In this study, a novel injectable electroactive hydrogel (NGP) based on sodium hyaluronate oxide (SAO) and polyaniline-grafted gelatine (NH2-Gel-PANI) was developed as a material in which to load neural stem cells (NSCs) and donepezil (DPL) to facilitate nerve regeneration after SCI. To evaluate the potential of the prepared NGP hydrogel in SCI repair applications, the surface morphology, self-repairing properties, electrical conductivity and cytocompatibility of the resulting hydrogel were analysed. Meanwhile, we evaluated the neural repair ability of NGP hydrogels loaded with DPL and NSCs using a rat model of spinal cord injury.
Results The NGP hydrogel has a suitable pore size, good biocompatibility, excellent conductivity, and injectable and self-repairing properties, and its degradation rate matches the repair cycle of spinal cord injury. In addition, DPL could be released continuously and slowly from the NGP hydrogel; thus, the NGP hydrogel could serve as an excellent carrier for drugs and cells. The results of in vitro cell experiments showed that the NGP hydrogel had good cytocompatibility and could significantly promote the neuronal differentiation and axon growth of NSCs, and loading the hydrogel with DPL could significantly enhance this effect. More importantly, the NGP hydrogel loaded with DPL showed a significant inhibitory effect on astrocytic differentiation of NSCs in vitro. Animal experiments showed that the combination of NGP hydrogel, DPL, and NSCs had the best therapeutic effect on the recovery of motor function and nerve conduction function in rats. NGP hydrogel loaded with NSCs and DPL not only significantly increased the myelin sheath area, number of new neurons and axon area but also minimized the area of the cystic cavity and glial scar and promoted neural circuit reconstruction.Conclusion sThe DPL- and NSC-laden electroactive hydrogel developed in this study is an ideal biomaterial for the treatment of traumatic spinal cord injury.
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ACS Nano
·
2023
·
IF 17.1
Hongfu Cao,Manyu Chen,Xiaolin Cui,Yuan Liu,Yuhan Liu,Siyan Deng,Tun Yuan,Yujiang Fan,Qiguang Wang,Xingdong Zhang
As chondrocytes from osteoarthritic cartilage usually exhibit aging and senescent characteristics, targeting aging chondrocytes could be a potential therapeutic strategy. In this study, exosomes derived from umbilical cord-derived mesenchymal stem cells (UCMSC-EXOs) combined with the chondrocyte-targeting capacity and controlled-release system were proposed for osteoarthritis (OA) treatment via rejuvenating aging chondrocytes. The essential functional miRNAs within UCMSC-EXOs were investigated, with the p53 signaling pathway identified as the key factor. To improve the therapeutic efficiency and retention time of UCMSC-EXOs in vivo, the exosomes (EXOs) were engineered on membranes with a designed chondrocyte-targeting polymers, and encapsulated within thiolated hyaluronic acid microgels to form a “two-phase” releasing system, which synergistically facilitated the repair of OA cartilage in a rat model. Together, this study highlighted the rejuvenating effects of UCMSC-EXOs on OA chondrocytes and the potential to combine with chondrocyte-targeting and sustained-release strategies toward a future cell-free OA treatment.
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Molecular Medicine Reports
·
2023
·Vol. 28
·期 3
·1-14
·
IF 3.4
Gui-Bo Liu,Yong-Xia Cheng,Hua-Min Li,Yong Liu,Li-Xin Sun,Qi Wu,Shang-Fu Guo,Ting-Ting Li,Chuan-Ling Dong,Ge Sun
Adipose tissue‑derived mesenchymal stem cells (ADMSCs) differentiate into cardiomyocytes and may be an ideal cell source for myocardial regenerative medicine. Ghrelin is a gastric‑secreted peptide hormone involved in the multilineage differentiation of MSCs. To the best of our knowledge, however, the role and potential downstream regulatory mechanism of ghrelin in cardiomyocyte differentiation of ADMSCs is still unknown. The mRNA and protein levels were measured by reverse transcription‑quantitative PCR and western blotting. Immunofluorescence staining was used to show the expression and cellular localization of cardiomyocyte markers and β‑catenin. RNA sequencing was used to explore the differentially expressed genes (DEGs) that regulated by ghrelin. The present study found that ghrelin promoted cardiomyocyte differentiation of ADMSCs in a concentration‑dependent manner, as shown by increased levels of cardiomyocyte markers GATA binding protein 4, α‑myosin heavy chain (α‑MHC), ISL LIM homeobox 1, NK2 homeobox 5 and troponin T2, cardiac type. Ghrelin increased β‑catenin accumulation in nucleus and decreased the protein expression of secreted frizzled‑related protein 4 (SFRP4), an inhibitor of Wnt signaling. RNA sequencing was used to determine the DEGs regulated by ghrelin. Functional enrichment showed that DEGs were more enriched in cardiomyocyte differentiation‑associated terms and Wnt pathways. Dead‑box helicase 17 (DDX17), an upregulated DEG, showed enhanced mRNA and protein expression levels following ghrelin addition. Overexpression of DDX17 promoted protein expression of cardiac‑specific markers and β‑catenin and enhanced the fluorescence intensity of α‑MHC and β‑catenin. DDX17 upregulation inhibited protein expression of SFRP4. Rescue assay confirmed that the addition of SFRP4 partially reversed ghrelin‑enhanced protein levels of cardiac‑specific markers and the fluorescence intensity of α‑MHC. In conclusion, ghrelin promoted cardiomyocyte differentiation of ADMSCs by DDX17‑mediated regulation of the SFRP4/Wnt/β‑catenin axis.
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JOURNAL OF HAZARDOUS MATERIALS
·
2023
·
IF 13.6
Cheng Zhang,Qinghai Zhang,Ming Luo,Qiuping Wang,Xiaomao Wu
Butylated hydroxytoluene (BHT), as an emerging contaminant in ecosystems, has potential influences on animals, aquatic organisms, and public health, and has been proven to be a major allelochemical of Pinellia ternata . In this study, Bacillus cereus WL08 was used to rapidly degrade BHT in liquid culture. Strain WL08 immobilized on tobacco stem charcoal (TSC) particles notably accelerated BHT removal in contract to its free cells, and exhibited excellent reutilization and storage capacities. The optimal removal parameters of TSC WL08 were ascertained to be pH 7.0, 30 °C, 50 mg L −1 BHT and 0.14 mg L −1 TSC WL08. Moreover, TSC WL08 significantly accelerated the degradation of 50 mg L −1 BHT in sterile and non-sterile soils compared to that of free WL08 or natural dissipation, and notably shortened their half-lives by 2.47- or 362.14- fold, and 2.20- or 14.99- fold, respectively. Simultaneously, TSC WL08 was introduced into the continuous cropping soils of P. ternata , which accelerated the elimination of allelochemical BHT, and notably enhanced the photosynthesis, growth, yield, and quality of P. ternata . This study provides new insights and strategies for the rapid in situ remediation of BHT-polluted soils and effective alleviation of P. ternata cropping obstacles.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Peipei Feng,Chaonan He,Guanrong Li,Jin Li,Yang Luo,Yaoqi Chen,Yun Tang,Jingyun Ma,Chunhai Ke
Cartilage repair remains a formidable challenge because of its limited regenerative capacity. Construction of a biomimetic hydrogel matrix that can induce cell aggregation is a promising therapeutic option. Cell aggregates are more beneficial than dissociated cells for improving survival and chondrogenic differentiation, thereby facilitating cartilage repair. Herein, we report a light-cured injectable composite hydrogel with cellular aggregation properties for cartilage defect repair that combines methacrylated chitosan (CSMA) and a methacrylate-modified decellularized extracellular matrix (dECMMA). The CSMA promotes cell aggregate formation by enhancing cadherin expression. The dECMMA retains many inherent components and bioactive factors, thereby providing a more natural microenvironment for cell proliferation and differentiation. By precisely adjusting the compositions of the CSMA and dECMMA, it was possible to fine-tune their physicochemical properties and biochemical cues. The results showed that a composite hydrogel composed of 2 % (m/v) CSMA and 5 % (m/v) dECMMA exhibited good injectability, appropriate degradability and mechanical properties, and regulated the formation of bone marrow mesenchymal stem cell aggregates. Transplantation of the composite hydrogel loaded with bone marrow mesenchymal stem cells (BMSCs) into a cartilage defect model demonstrated effective hyaline cartilage repair. Thus, light-cured injectable composite hydrogels embedded with BMSCs holds clinical promise for cartilage defect repair.
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