Nano Materials Science
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2024
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IF 12.6
Ming Deng,Geliang Hu,Fan Liang,Qi Liao,Wanjun Ding,Bin He,Jianghua Ming,Hui Huang,Junqi Liu,Zhaohong Kong,Ping Xie
Objective To investigate the repair of spinal cord injury (SCI) in rats using 3D bioprinted decellularized extracellular matrix (dECM) hydrogel, neural stem cells (NSCs), and TGF-β1 monoclonal antibody. Methods The spinal cord-derived dECM hydrogel (SC-dECM-gel) was optimized for 3D printing. Rheological tests established a 3 % concentration as optimal. In vitro tests assessed the effects of TGF-β1 monoclonal antibody on NSC viability and differentiation. A rat SCI model was treated with the printed gel, and recovery was monitored using the Basso-Beattie-Bresnahan test and evoked potentials. Results The 3 % SC-dECM-gel showed superior rheological properties. TGF-β1 monoclonal antibody enhanced NSC survival and differentiation in vitro. In vivo, the 3D bioprinted gel significantly improved motor function and promoted neuronal regeneration. Conclusion 3D bioprinted SC-dECM-gel loaded with NSCs and TGF-β1 monoclonal antibody effectively restores motor function and promotes regeneration in SCI rats, offering a promising approach for SCI treatment.
研究领域:
再生医学
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神经科学
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生物材料学
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Stem Cell Research & Therapy
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2026
·Vol. 17
·期 1
·123
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IF 7.8
Du Mengxian,Guo Fengyi,Liu Xinna,Zhang Shiqi,Zhang Di,Qiu Leyi,Zhang Jingyang,Li Baoqiang,Yuan Huiping
Background Normal tension glaucoma (NTG) causes progressive retinal ganglion cell (RGC) loss without elevated intraocular pressure, and currently lacks effective neuroprotective therapies. OPTN(E50K) mutation, a pathogenic gene of NTG, compromises paracrine trophic capacity in bone marrow (BM) stem cells. Allogeneic young BM stem cells can provide trophic support and exhibit therapeutic potential; however, their clinical application is limited by immunogenic rejection and tumorigenic risks, prompting a renewed interest in rejuvenate autologous BM stem cells strategy. Methods To address these challenges, we developed a composite chitosan-rapamycin (RAPA) carbon dots (CRCD) to restore the reparative potential of autologous BM stem cells. BM stem cells from aged OPTN(E50K) mice were isolated, clustered and treated with CRCD before validated their changes of neurotrophic factors expression as well as oxidative stress and autophagy indicators. Then we assessed their impact on co-cultured retinas in vitro. Transplantation were performed into lethally irradiated age-matched OPTN(E50K) hosts with CRCD-pretreated autologous BM stem cells via tail vein injection, and generated stable chimeric models. Neurotrophic factors and neuron apoptosis analyses were performed, followed by the visual behavioral tests. Results Our results demonstrated that CRCD pretreatment enhanced autophagy, reduced oxidative stress, and augmented paracrine neurotrophic release. In vitro, these cells reduced retinal ganglion cell apoptosis and promoted neurotrophic factor expression in co-cultured retinal explants. In vivo, comparative analysis revealed that CRCD intervention significantly elevated neurotrophic factor expression in retinal tissues compared to RAPA-treated and untreated chimeras. Functional assessments further confirmed superior visual performance in CRCD-Sca-1 + chimeras, correlating with improved RGC survival. Conclusion These findings suggest that CRCD improved paracrine neurotrophic support of autologous BM stem cells by enhancing their autophagy and paracrine functions, leading to structural and functional rescue of the glaucomatous retina. This approach offered a clinically relevant strategy for NTG, providing sustained neuroprotection while avoiding the risks of allogeneic transplantation and repeated intravitreal drug delivery. Graphical The alternative text for this image may have been generated using AI.
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COMPOSITES PART B-ENGINEERING
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2023
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IF 13.1
Yang Liu,Wen Zhang,Cheng Hu,Cheng Zheng,Fanjun Zhang,Li Yang,Zhengyong Li,Yunbing Wang
Stem cell transplantation can replace lost and damaged neurons after ischemic stroke and has been proposed as a potential treatment for stroke. However, stem cell therapy is challenged by poor cell retention, survival, and differentiation following transplantation. In this study, we developed a composite hydrogel incorporating brain decellularized extracellular matrix (dECM) and a matrix metallopeptidase (MMP)-responsive host–guest (HG) hydrogel that acts as a platform for human induced pluripotent stem cell-derived neural stem cells (iPSC-NSCs) delivery to improve transplant stem cell survival and differentiation. The optimized composite hydrogel ratio was screened by rheology analysis and neurite outgrowth assessment. We then examined the effects of HG/dECM composite hydrogels on iPSC-NSCs survival and differentiation on two-dimensional surfaces modified with hydrogel and in a three-dimensional hydrogel network. Moreover, iPSC-NSCs-laden composite hydrogels were injected into the infarct cavity in an ischemic stroke model to replace lost and damaged nerve cells. As expected, the HG/dECM composite hydrogels better facilitated the survival and differentiation of iPSC-NSC in vivo than the control. Likewise, the iPSC-NSCs loaded in HG/dECM composite hydrogels showed superior retention and survival in the cortical infarct cavity, and the composite hydrogels promoted the differentiation of iPSC-NSCs into neurons. Overall, HG/dECM composite hydrogels are a promising platform to regulate stem cell survival and differentiation.
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International Journal of Nanomedicine
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2023
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IF 8
Zhan Su,Duanqin Liu,Liying Chen,Jun Zhang,Lu Ru,Zhiyu Chen,Zhennan Gao,Xuxia Wang
Background Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant tumor in the world. Studies in recent years have demonstrated that cancer stem cells (CSCs) are present in many tumor tissues, including HNSCC, and CSCs are the root cause of tumor recurrence and metastasis. Thus, taking new treatment measures to target the killing of CSCs that are resistant to chemotherapy and radiotherapy is key to the success of cancer treatment.Methods We explored a method for preparing anti-CD44 antibody-modified superparamagnetic iron oxide nanoparticles (SPIONPs). Biocompatibility was evaluated by a CCK-8 assay. The CSCs were obtained by a 3D cell culture technique from Cal-27 (human oral squamous cell carcinoma) cells, and then the CSCs were identified by quantitative real-time polymerase chain reaction (qRT-PCR). The targeting efficiency of the CD44-SPIONPs to CSCs was confirmed by Prussian blue staining and visualized by laser scanning confocal microscopy (LSCM). Flow cytometry was used to detect the apoptosis of CSCs after alternating magnetic field (AMF) treatment. The efficacy of tumor growth inhibition by CD44-SPIONP-mediated magnetic hyperthermia therapy was evaluated with tumor xenografts in nude mice.Results The CD44-SPIONPs exhibited no negative effect on CSCs, indicating good biocompatibility. After SPIONPs were cocultured with stem cells, the majority of CD44-SPIONPs labeled with FITC penetrated the cell membrane into the cytoplasm. After AMF treatment, CD44-SPIONPs induced CSCs to undergo programmed death. The inhibitory ratio of the treated group was 33.43%, and necrotic areas in the tumor tissue were mainly distributed around the magnetic fluid.Conclusion These results demonstrate that it is possible to kill CSCs using targeted magnetic nanoparticles and an AMF and that magnetic fluid hyperthermia significantly inhibited the growth of grafted Cal-27 tumors in mice.
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JOURNAL OF WUHAN UNIVERSITY OF TECHNOLOGY-MATERIALS SCIENCE EDITION
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2023
·Vol. 37
·期 6
·1271-1278
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IF 1.6
Luo Zhang,Gong Chaihong,Mao Xiaowei,Wang Zhe,Liu Zhifan,Ben Yali,Zhang Weiying
Keratinocytes and fibroblasts, derived from hiPSCs, were used to construct the human epidermal model by a culture patch made by monolayer poly-(lactic-co-glycolic acid) (PLGA) nanofibers and a human skin-on-a-chip device. Unlike the conventional culture dish method, two different epidermal cells are successfully adhered to the front and back sides of the patch, which produces a three-dimensional nanofibrous scaffold similar to a natural extracellular matrix before the patch was cultured in the skin-on-a-chip device to mimic the physiological conditions of human skin. As expected, the differentiated hiPSCs show the expression of keratinocyte- and fibroblast- specific proteins on the patch, and the layering is found between these two kinds of cells, indicating that this approach creates a powerful in vitro system for modeling skin development and diseases.
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2022
·Vol. 23
·期 23
·14831
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IF 6.208
Aiyun Yang,Shen Li,Yan Zhang,Xiuwei Wang,Zhen Guan,Zhiqiang Zhu,Yingchao Liang,Lijiao Zhao,Jianhua Wang
Neural-tube defects (NTDs) are one type of the most serious birth defects. Studies have shown that inositol deficiency is closely related to the occurrence of NTDs. Bone morphogenetic protein (BMP)-mediated Smad signaling pathways have been implicated in neurogenesis and neural-tube closure. However, the role of the BMP/Smad pathway in inositol-deficiency-induced NTDs remains unclear. Inositol-deficiency models in C57 mice and mouse neural stem cells (mNSCs) were induced with Li2CO3treatment or inositol withdrawal. The role of the BMP/Smad pathway in the regulation of cell proliferation and the development of NTDs was determined utilizing qRT-PCR, HE staining, Western blot, immunostaining, MTT assay, EdU staining, and flow cytometry. The intraperitoneal injection of Li2CO3at Embryonic Day 7.5 induced the occurrence of NTDs. The mRNA levels ofBmp2,Bmp4,Smad1,Smad5,Smad8andRunx2, the phosphorylation of Smad1/5/8, and the nuclear translocation of Runx2 were significantly increased in NTD embryonic brain tissues and mNSCs exposed to Li2CO3or an inositol-free medium, which were suppressed by BMP receptor selective inhibitor LDN-193189. The Li2CO3-induced phosphorylation of Smad1/5/8 was inhibited by inositol supplementation. Cell proliferation was significantly promoted by Li2CO3exposure or the absence of inositol in mNSCs, which was reversed by LDN-193189. These results suggest that the activation of the BMP/Smad signaling pathway might play an important role in the development of NTDs induced by maternal Li2CO3exposure via inositol deficiency.Keywords:inositol;BMP signaling;neural-tube defects;neural stem cell;proliferation
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Aging and Disease
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2023
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IF 7.4
Guoxiang Liu,Xiaoxia Li,Fanghao Yang,Jingyu Qi,Lipeng Shang,Huhu Zhang,Shuang Li,Fenghua Xu,Lingne Li,Huaxin Yu,Yang Li,Xiaolei Dong,Qinghang Song,Feng Zhu,Guang Chen,Can Cao,Liangqian Jiang,Junzhe Su,Lina Yang,Xiaohui Xu,Zhe Zhang,Robert Chunhua Zhao,Bing Li
The senescence of mesenchymal stem cells (MSCs) impairs their regenerative capacity to maintain tissue homeostasis. Numerous studies are focusing on the interventions and mechanisms to attenuate the senescence of MSCs. C-phycocyanin (C-PC) is reported to have multiple functions such as antitumor, antioxidation, anti-inflammation and anti-aging roles, but there is little research about the effects of C-PC on the senescence of MSCs. Here we investigated the roles and mechanism of C-PC on MSCs senescence. In vitro results showed that C-PC could reduce senescence, enhance proliferation, promote the adipogenic and osteogenic differentiation in senescent MSCs induced by oxidative stress. In vivo D-Galactose (D-Gal) induced rats aging models showed C-PC also increased the viability and differentiation of intrinsic senescent bone marrow derived MSCs (BMSCs). Furthermore, C-PC also decreased the levels of oxidative stress markers ROS or MDA, elevated the SOD activity, and increased the anti-inflammatory factors. Proteomic chip analysis showed that C-PC interacted with ZDHHC5, and their interaction was verified by pull down assay. Overexpression of ZDHHC5 aggravated the senescence of MSCs and greatly lessened the beneficial effects of C-PC on senescence. In addition, we found ZDHHC5 regulated autophagy by altering LC3, Beclin1 and PI3K/AKT/mTOR pathway. In summary, our data indicated that C-PC ameliorates the senescence of MSCs through zinc finger Asp-His-His-Cys (DHHC) domain-containing protein 5 (ZDHHC5) mediated autophagy via PI3K/AKT/mTOR pathway. The present study uncovered the key role of autophagy in MSCs senescence and PI3K/AKT/mTOR pathway may be a potential target for anti-senescence studies of MSCs.
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Stem Cells International
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2022
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IF 5.131
Jinyong Chen,Feng Liu,Wangxing Hu,Yi Qian,Dilin Xu,Chenyang Gao,Zhiru Zeng,Si Cheng,Lan Xie,Kaixiang Yu,Gangjie Zhu,Xianbao Liu
Background. The poor survival rates of transplanted mesenchymal stem cells (MSCs) in harsh microenvironments impair the efficacy of MSCs transplantation in myocardial infarction (MI). Extrinsic apoptosis pathways play an important role in the apoptosis of transplanted MSCs, and Fas apoptosis inhibitory molecule (FAIM) is involved in regulation of the extrinsic apoptosis pathway. Thus, we aimed to explore whether FAIM augmentation protects MSCs against stress-induced apoptosis and thereby improves the therapeutic efficacy of MSCs. Methods. We ligated the left anterior descending coronary artery (LAD) in the mouse heart to generate an MI model and then injected FAIM-overexpressing MSCs (MSCsFAIM) into the peri-infarction area in vivo. Moreover, FAIM-overexpressing MSCs were challenged with oxygen, serum, and glucose deprivation (OGD) in vitro, which mimicked the harsh microenvironment that occurs in cardiac infarction. Results. FAIM was markedly downregulated under OGD conditions, and FAIM overexpression protected MSCs against OGD-induced apoptosis. MSCsFAIM transplantation improved cell retention, strengthened angiogenesis, and ameliorated heart function. The antiapoptotic effect of FAIM was mediated by cellular-FLICE inhibitory protein (c-FLIP), and FAIM augmentation improved the protein expression of c-FLIP by reducing ubiquitin–proteasome-dependent c-FLIP degradation. Furthermore, FAIM inhibited the activation of JNK, and treatment with the JNK inhibitor SP600125 abrogated the reduction in c-FLIP protein expression caused by FAIM silencing. Conclusions. Overall, these results indicated that FAIM curbed the JNK-mediated, ubiquitination–proteasome-dependent degradation of c-FLIP, thereby improving the survival of transplanted MSCs and enhancing their efficacy in MI. This study may provide a novel approach to strengthen the therapeutic effect of MSC-based therapy.
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Acta Biomaterialia
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2022
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IF 10.633
Tingben Huang,Chenxi Tu,Tong Zhou,Zhou Yu,Yuchen Wang,Qiong Yu,Ke Yu,Zhiwei Jiang,Changyou Gao,Guoli Yang
As an alternative strategy to achieve the desired bone augmentation, tenting screw technology (TST) has considerably broadened the indications for implant treatment. Titanium tenting screws are typically used in TST to maintain the space for bone regeneration . However, a high degree of osteogenic integration complicate titanium tenting screw removal and impact the bone healing micro-environment. Previous efforts have been focused on modifying titanium surfaces to enhance osseointegration while ignoring the opposite process. Due to the vital role of bone marrow mesenchymal stem cells (BMSCs) in bone regeneration, it might be feasible to reduce osseointegration around titanium tenting screws by resisting the adhesion of BMSCs. Herein, poly(ethylene glycol)methyl ether methacrylate (poly(PEGMA)) with an optimal length of PEG chain was incorporated with a Ti surface in terms of surface-initiated activators regenerated by electron transfer atom transfer radical polymerization (SI-ARGET ATRP). The cell apoptosis analysis showed that the new surface would not induce the apoptosis of BMSCs. Then, the adhesive and proliferative behaviors of BMSCs on the surface were analyzed which indicated that the poly(PEGMA) surface could inhibit the proliferation of BMSCs through resisting the adhesion process. Furthermore, in vivo experiments revealed the presence of the poly(PEGMA) on the surface resulted in a lower bone formation and osseointegration compared with the Ti group. Collectively, this dense poly(PEGMA) surface of Ti may serve as a promising material for clinical applications in the future. Statement of significance The poly(ethylene glycol)methyl ether methacrylate (poly(PEGMA)) with an optimal length of PEG chain was grafted onto a Ti surface by surface-initiated activators regenerated by electron transfer atom transfer radical polymerization (SI-ARGET ATRP). The PEGMA surface could reduce the osteogenic integration by preventing the adhesion of cells, resulting in a lower pullout force of the modified implant and thereby desirable and feasible applications in dental surgery.
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Frontiers in Bioengineering and Biotechnology
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2022
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IF 6.064
Qin Xiaoyan,Wu Yixin,Liu Shuang,Yang Lei,Yuan Hongxia,Cai Susu,Flesch Julia,Li Zehao,Tang Yujing,Li Xiaomin,Zhuang Yi,You Changjiang,Liu Chaoyong,Yu Changyuan
Polycaprolactone (PCL) has been widely used as a scaffold material for tissue engineering. Reliable applications of the PCL scaffolds require overcoming their native hydrophobicity and obtaining the sustained release of signaling factors to modulate cell growth and differentiation. Here, we report a surface modification strategy for electrospun PCL nanofibers using an azide-terminated amphiphilic graft polymer. With multiple alkylation and pegylation on the side chains of poly-L-lysine, stable coating of the graft polymer on the PCL nanofibers was achieved in one step. Using the azide-alkyne “click chemistry”, we functionalized the azide-pegylated PCL nanofibers with dibenzocyclooctyne-modified nanocapsules containing growth factor, which rendered the nanofiber scaffold with satisfied cell adhesion and growth property. Moreover, by specific immobilization of pH-responsive nanocapsules containing bone morphogenetic protein 2 (BMP-2), controlled release of active BMP-2 from the PCL nanofibers was achieved within 21 days. When bone mesenchyme stem cells were cultured on this nanofiber scaffold, enhanced ossification was observed in correlation with the time-dependent release of BMP-2. The established surface modification can be extended as a generic approach to hydrophobic nanomaterials for longtime sustainable release of multiplex signaling proteins for tissue engineering.
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Stem Cell Research & Therapy
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2022
·Vol. 13
·期 1
·1-19
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IF 8.079
Lin Yifeng,Dong Shunni,Ye Xiaohang,Liu Juan,Li Jiaqun,Zhang Yanye,Tu Mixue,Wang Siwen,Ying Yanyun,Chen Ruixue,Wang Feixia,Ni Feida,Chen Jianpeng,Du Binyang,Zhang Dan
Background Thin endometrium is a primary cause of defective endometrial receptivity, resulting in infertility or recurrent miscarriage. Much effort has been devoted toward regenerating thin endometrium by stem cell-based therapies. The human placenta-derived mesenchymal stem cells (HP-MSCs) are emerging alternative sources of MSCs with various advantages. To maximize their retention inside the uterus, we loaded HP-MSCs with cross-linked hyaluronic acid hydrogel (HA hydrogel) to investigate their therapeutic efficacy and possible underlying mechanisms.
Methods Ethanol was injected into the mice uterus to establish the endometrium-injured model. The retention time of HP-MSCs and HA hydrogel was detected by in vivo imaging, while the distribution of HP-MSCs was detected by immunofluorescence staining. Functional restoration of the uterus was assessed by testing embryo implantation rates. The endometrial morphological alteration was observed by H&E staining, Masson staining, and immunohistochemistry. In vitro studies were further conducted using EdU, transwell, tube formation, and western blot assays. Results Instilled HP-MSCs with HA hydrogel (HP-MSCs-HA) exhibited a prolonged retention time in mouse uteri than normal HP-MSCs. In vivo studies showed that the HP-MSCs-HA could significantly increase the gland number and endometrial thickness ( P < 0.001, P < 0.05), decrease fibrous area ( P < 0.0001), and promote the proliferation and angiogenesis of endometrial cells (as indicated by Ki67 and VEGF, P < 0.05, P < 0.05, respectively) in mice injured endometrium. HP-MSCs-HA could also significantly improve the embryo implantation rate ( P < 0.01) compared with the ethanol group. Further mechanistic study showed the paracrine effects of HP-MSCs. They could not only promote the proliferation and migration of human endometrial stromal cells via the JNK/Erk1/2-Stat3-VEGF pathway but also facilitate the proliferation of glandular cells via Jak2-Stat5 and c-Fos-VEGF pathway. In turn, the increased VEGF in the endometrium promoted the angiogenesis of endothelial cells. Conclusion Our study suggested the potential therapeutic effects and the underlying mechanisms of HP-MSCs-HA on treating thin endometrium. HA hydrogel could be a preferable delivery method for HP-MSCs, and the strategy represents a promising therapeutic approach against endometrial injury in clinical settings. Graphical abstract
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JOURNAL OF ENDODONTICS
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2023
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IF 4.2
Ruoman Xu,Ziyu Zhou,Danle Lin,Lingling Yuan,Siyu Wang,Meng Xu,Yanan Chen,Xiaoli Hu
Introduction Chondroitin sulfate (CS) is a major proteoglycan involved in the mineralization of the organic matrix of dentin. In this study, the roles of CS immobilized in cross-linked collagen I (Col I) hydrogels on odontogenic differentiation of dental pulp stem cells (DPSCs) and reparative dentin formation were investigated. Methods Different concentrations of CS were incorporated into the genipin–cross-linked Col I hydrogels (CS-0.05, CS-0.1, and CS-0.2, respectively). The influences of CS on the proliferation and odontogenic differentiation of DPSCs were investigated. Finally, the effect of the functionalized hydrogel on the formation of reparative dentin was analyzed in a rat pulp capping model in vivo . Results CS improved the proliferation of DPSCs seeded on the hydrogels ( P < .05). CS also enhanced the mineralization activities and increased the expression levels of the odontogenic-related proteins of DPSCs on days 7 and 14 ( P < .05). In vivo , CS-0.1 hydrogel induced reparative dentin formation with higher quality compared with mineral trioxide aggregate . Conclusions CS immobilized in Col I hydrogels could induce odontogenic differentiation of DPSCs in vitro and promote homogeneous mineralized barrier formation in vivo . CS–Col I hydrogel has the potential for reparative dentin formation of high quality in direct pulp capping.
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