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COMPOSITES PART B-ENGINEERING · 2022 · IF 11.322

Modulated integrin signaling receptors of stem cells via ultra-soft hydrogel for promoting angiogenesis

Zhimo Liu,Binfan Zhao,Liucheng Zhang,Shutong Qian,Jiayi Mao,Liying Cheng,Xiyuan Mao,Zhengwei Cai,Yuguang Zhang,Wenguo Cui,Xiaoming Sun

Integrin is a widely distributed adhesion molecule on cell membrane surface, which plays a role in transferring mechanical properties signals of the extracellular matrix into cells during cell adhesion to the extracellular matrix. In this study, by introducing long-chain polyethylene glycol molecules that can be photo-crosslinked into gelatin chains, ultra-soft hydrogel that can simulate soft tissue in vivo is constructed and stimulated by "low matrix stiffness" of the integrin signaling pathway, to promote the vascularization function of stem cells. The storage modulus of the ultra-soft hydrogel at room temperature is as low as 3.24 ± 0.18 Pa and as high as 40.83 ± 1.32 Pa. In vitro experiments showed that the stiffness of hydrogel affects the activation of the phosphorylation of VEGFR by regulating the phosphorylation of integrin and further controls the activation of the ERK pathway, thus regulating the vascularization of ADSCs . In vivo experiments have proved that ADSCs encapsulated in PEG-Gel have excellent performance in repairing skin flaps. The ultra-soft hydrogel can promote the vascularization of ADSCs by activating the "extracellular matrix stiffness-integrin-VEGFR-ERK" regulatory pathway, which is a potential regenerative repair material for promoting the application of stem cells in skin flap repair.

研究领域: 生物材料 · 组织工程 · 干细胞生物学 · 再生医学
✓ 已验证 DOI 高影响因子
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Brain Sciences · 2022 ·Vol. 12 ·期 12 ·1620 · IF 3.333

Hydrogels to Support Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells

Ying Wei,Uwimana Alexandre,Xiang Ma

Purpose: Retinal pigment epithelial (RPE) cells are highly specialized neural cells with several functions essential for vision. Progressive deterioration of RPE cells in elderly individuals can result in visual impairment and, ultimately, blinding disease. While human embryonic stem cell-derived RPE cell (hESC-RPE) growth conditions are generally harsher than those of cell lines, the subretinal transplantation of hESC-RPE is being clinically explored as a strategy to recover the damaged retina and improve vision. The cell-adhesion ability of the support is required for RPE transplantation, where pre-polarized cells can maintain specific functions on the scaffold. This work examined four typical biodegradable hydrogels as supports for hESC-RPE growth. Methods: Four biodegradable hydrogels were examined: gelatin methacryloyl (GelMA), hyaluronic acid methacryloyl (HAMA), alginate, and fibrin hydrogels. ARPE-19 and hESC-RPE cells were seeded onto the hydrogels separately, and the ability of these supports to facilitate adherence, proliferation, and homogeneous distribution of differentiated hESC-RPE cells was investigated. Furthermore, the hydrogel’s subretinal bio-compatibility was assessed in vivo. Results: We showed that ARPE-19 and hESC-RPE cells adhered and proliferated only on the fibrin support. The monolayer formed when cells reached confluency, demonstrating the polygonal semblance, and revealing actin filaments that moved along the cytoplasm. The expression of tight junction proteins at cell interfaces on the 14th day of seeding demonstrated the barrier function of epithelial cells on polymeric surfaces and the interaction between cells. Moreover, the expression of proteins crucial for retinal functions and matrix production was positively affected by fibrin, with an increment of PEDF. Our in vivo investigation with fibrin hydrogels revealed high short-term subretinal biocompatibility. Conclusions: The research of stem cell-based cell therapy for retinal degenerative diseases is more complicated than that of cell lines. Our results showed that fibrin is a suitable scaffold for hESC-RPE transplantation, which could be a new grafting material for tissue engineering RPE cells.Keywords:hESC-RPE;transplantation;hydrogel;retinal degenerative diseases;ARPE-19

✓ 已验证 DOI PubMed 高影响因子
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Scientific Reports · 2017 ·Vol. 7 ·期 1 ·1-8 · IF 4.259

Modeling Congenital Hyperinsulinism with ABCC8-Deficient Human Embryonic Stem Cells Generated by CRISPR/Cas9

Guo Dongsheng,Liu Haikun,Ruzi Aynisahan,Gao Ge,Nasir Abbas,Liu Yanli,Yang Fan,Wu Feima,Xu Guosheng,Li Yin-xiong

Congenital hyperinsulinism (CHI) is a rare genetic disorder characterized by excess insulin secretion, which results in hypoglycemia. Mutation of sulfonylurea receptor 1 (SUR1), encoded by the ABCC8 gene, is the main cause of CHI. Here, we captured the phenotype of excess insulin secretion through pancreatic differentiation of ABCC8 -deficient stem cells generated by the CRISPR/Cas9 system. ABCC8- deficient insulin-producing cells secreted higher insulin than their wild-type counterparts, and the excess insulin secretion was rescued by nifedipine, octreotide and nicorandil. Further, we tested the role of SUR1 in response to different potassium levels and found that dysfunction of SUR1 decreased the insulin secretion rate in low and high potassium environments. Hence, pancreatic differentiation of ABCC8- deficient cells recapitulated the CHI disease phenotype in vitro , which represents an attractive model to further elucidate the function of SUR1 and to develop and screen for novel therapeutic drugs.

研究领域: 遗传学 · 干细胞研究 · 分子生物学 · 内分泌学
✓ 已验证 DOI PubMed 高影响因子
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Journal of Materials Chemistry B · 2020 ·Vol. 8 ·期 34 ·7713-7722 · IF 5.344

In situ activated mesenchymal stem cells (MSCs) by bioactive hydrogels for myocardial infarction treatment

Long Gao,Min Yi,Min Xing,Hekai Li,Yanling Zhou,Qing Xu,Zhaowenbin Zhang,Zhanpeng Wen,Jiang Chang

Stem-cell therapy has been proved as a promising strategy for myocardial infarction (MI) treatment. However, the therapeutic efficacy is mainly limited by the cellular activity of transplanted mesenchymal stem cells (MSCs). In this study, a novel bioglass (BG)/γ-polyglutamic acid (γ-PGA)/chitosan (CS) hydrogel was obtained by in situ adding BG to stimulate the imine bond formation. And the effect of the composite hydrogel on MI therapeutic efficacy was evaluated in a rat acute myocardial infarction (AMI) model in vivo and the possible mechanism of the BG/γ-PGA/CS hydrogel for the stimulation of the intercellular interaction between MSCs and cardiomyocytes (CMs) was explored by a MSC and CM co-culture experiment in vitro. The implantation of the MSC loaded BG/γ-PGA/CS composite hydrogel in the mice AMI model showed a significant improvement in the therapeutic efficacy with improved cardiac function, attenuation of heart remodeling, reduced cardiomyocyte apoptosis and accelerated vascularization. The in vitro cell experiments demonstrated that the BG/γ-PGA/CS hydrogel activated the intercellular interaction between MSCs and CMs, which resulted in reduced cell apoptosis and enhanced angiogenesis. Silicate based bioactive hydrogels activated MSCs and cell–cell interactions in cardiac tissue after AMI and significantly enhanced the efficacy, which suggests that this bioactive hydrogel based approach is an effective way to enhance stem-cell therapy.

研究领域: 生物医学工程 · 组织工程 · 干细胞治疗 · 心脏病学
✓ 已验证 DOI PubMed 高影响因子
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Applied Bionics and Biomechanics · 2020 · IF 1.141

Bionic Silk Fibroin Film Induces Morphological Changes and Differentiation of Tendon Stem/Progenitor Cells

Kang Lu,Xiaodie Chen,Hong Tang,Mei Zhou,Gang He,Juan Liu,Xuting Bian,Yupeng Guo,Fan Lai,Mingyu Yang,Zhisong Lu,Kanglai Tang

Purpose. Tendon injuries are common musculoskeletal system disorders, but the ability for tendon regeneration is limited. Silk fibroin (SF) film may be suitable for tendon regeneration due to its excellent biocompatibility and physical properties. This study is aimed at evaluating the application value of bionic SF film in tendon regeneration. Methods. Tendon stem/progenitor cells (TSPCs) were isolated from rat Achilles tendon and characterized based on their surface marker expression and multilineage differentiation potential. SF films with smooth or bionic microstructure surfaces (5, 10, 15, 20 μm) were prepared. The morphology and mechanical properties of natural tendons and SF films were characterized. TSPCs were used as the seed cells, and the cell viability and cell adhesion morphology were analyzed. The tendongenesis-related gene expression of TSPCs was also evaluated using quantitative polymerase chain reaction. Results. Compared to the native tendon, only the 10, 15, and 20 μm SF film groups had comparable maximum loading and ultimate stress, with the exception of the breaking elongation rate. The 10 μm SF film group had the highest percentage of oriented cells and the most significant changes in cell morphology. The most significant upregulations in the expression of COL1A1, TNC, TNMD, and SCX were also observed in the 10 μm SF film group. Conclusion. SF film with a bionic microstructure can serve as a tissue engineering scaffold and provide biophysical cues for the use of TSPCs to achieve proper cellular adherence arrangement and morphology as well as promote the tenogenic differentiation of TSPCs, making it a valuable customizable biomaterial for future applications in tendon repair.

✓ 已验证 DOI PubMed 高影响因子
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Journal of Materials Chemistry B · 2026 · IF 6.2

An adipose-derived mesenchymal stem cell-loaded polysaccharide hydrogel promotes wound healing through angiogenesis

Shengke Zhu,Wei Li,Kangan Wang,Bin Hu,Shenggang Huang,Jiahao Yang,Peng Fan,Shige Wang,Yu Sun,Chunping Zhu

Wound repair is a coordinated and sequential biological process involving multiple cells and phases, with inflammation, vascularization, re-epithelialization, collagen deposition, and remodeling being critical stages. Mesenchymal stem cells, capable of sensing the wound microenvironment and secreting cytokines to regulate the repair process, have garnered significant attention in wound repair. This study developed a self-healing polysaccharide-based hydrogel system using two widely sourced polysaccharides. The main components of the hydrogel are oxidized dextran (OD) and carboxymethyl chitosan (CMCS). This hydrogel features a simple preparation process and favorable biocompatibility, serving as a carrier for cell culture to enable three-dimensional (3D) cultivation of adipose-derived mesenchymal stem cells (ADSCs). Experiments on full-thickness skin defect repair in nude mice demonstrated that the ADSC-loaded polysaccharide hydrogel (OC-ADSCs) significantly promoted wound closure, collagen deposition, epidermal regeneration, as well as angiogenesis and vessel maturation. The OC-ADSC hydrogel can function as a novel cell delivery system, synergistically promoting wound healing and tissue regeneration by modulating the wound microenvironment, showing potential for clinical translation.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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EXPERIMENTAL AND MOLECULAR PATHOLOGY · 2026 · IF 4.1

Resveratrol targeting Smad4 via a concentration-dependent biphasic effect regulates stem cells-mediated regeneration

Ziqing Zhou,Shaoming Wu,Xiaoran Zhang,Guanbin Chen,Hengyue Ma,Ming Li,Yuchuan Liu,Ting Wang

Resveratrol (RSV), a globally utilized nutraceutical compound, is primarily recognized for its human health benefits, contributing to its widespread and often unregulated use in daily life and clinical settings. However, its influence on cellular stemness remains poorly understood. While numerous reports suggest anti-tumor properties, systematic and robust evidence is lacking. This study employed high-throughput RNA sequencing, RNA interference, RT-qPCR, and whole-mount in situ hybridization, and used the planarian Dugesia japonica as a stem cell model, aiming to investigate the effects of varying RSV concentrations on blastema regeneration following amputation and analyze the associated mechanism. We demonstrated a biphasic effect of RSV on anterior blastema regeneration: low-concentration RSV (5 μM) promoted regeneration, whereas high-concentration RSV (50 μM) caused significant inhibition. RNA-seq identified Smad4 as a key mediator; its inhibition exacerbated the regenerative deficit under low concentration. Intriguingly, PiwiA expression increased in the anterior blastema at both RSV concentrations, most notably at low concentration condition. Conversely, the late stem cell marker Agat1 was significantly suppressed by high-concentration RSV. These findings indicated that RSV promoted stem cell proliferation. Critically, low-concentration RSV enhanced both proliferation and differentiation, while high-concentration RSV inhibited differentiation independently of Smad4 . This study provided the first in vivo evidence at the whole-organism level that RSV concentration dictated divergent stem cell differentiation fates, offering a scientific basis for its rational evaluation and application.

CAS / MDL: 501-36-0
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF CONTROLLED RELEASE · 2026 · IF 12.4

Nanoceria drive stem cell hepatic differentiation and microenvironment remodeling for acute liver failure therapy

Fenfang Li,Guipan Chen,Tiantian Xue,Yuhan Jiang,Yurong Chai,Ke Yi,Yanteng Xu,Yuanyuan Jin,Yixin Zhang,Yuechen Luo,Haixia Wang,Enguo Ju,Zhuanggui Chen,Xi Xie,Yanglong Hou,Xintao Shuai,Kai Li,Mingqiang Li,Yu Tao

Stem cell-derived hepatocyte therapy holds great potential for treating acute liver failure (ALF) by rapidly restoring liver function and stimulating regeneration. However, significant challenges remain in efficiently driving stem cells toward a hepatic lineage and ensuring transplanted cell survival and functionality in the hostile, injured liver microenvironment. To overcome these hurdles, we developed a novel ceria nanoparticle@microRNA complex that facilitates hepatic differentiation of mesenchymal stem cells. We show that ceria nanozymes synergize with microRNA-122 to enhance hepatic differentiation by maintaining redox homeostasis and boosting mitochondrial biogenesis via TCF7L2 suppression, providing direct evidence that ceria nanoparticles can promote stem cell hepatic lineage commitment. Furthermore, we coated the resulting induced hepatocyte-like cells with a cerium-tannic acid metal-phenolic network, which protected the cells from oxidative damage under liver failure conditions. In a carbon tetrachloride-induced acute liver failure mouse model, this integrated strategy significantly restored liver function and promoted tissue regeneration. Overall, this study establishes a new bio-nano approach for stem cell-based liver therapy and offers fundamental insights into how bioactive nanomaterials can orchestrate stem cell differentiation and microenvironment remodeling, highlighting a conceptually innovative strategy with translational potential.

CAS / MDL: 30525-89-4 67-56-1
✓ 已验证 产品关联 DOI PubMed 高影响因子
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EUROPEAN JOURNAL OF ORAL SCIENCES · 2019 ·Vol. 127 ·期 3 ·210-221 · IF 1.81

Effect of metformin on human periodontal ligament stem cells cultured with polydopamine-templated hydroxyapatite

Zun Yang,Xiang Gao,Mengjiao Zhou,Yunchun Kuang,Mingli Xiang,Jie Li,Jinlin Song

Polydopamine-templated hydroxyapatite (tHA) is a type of nano-biomaterial that can promote osteogenesis in bone tissue engineering. However, high concentrations of tHA stimulate production of reactive oxygen species (ROS), resulting in cell injury and apoptosis. Metformin has been demonstrated to activate the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, which induces autophagy and decreases ROS production to prevent apoptosis. The present study was performed to investigate the potential application of tHA in combination with metformin in periodontal bone tissue engineering. Human periodontal ligament stem cells (hPDLSCs) were exposed to tHA in the presence or absence of metformin, and cytocompatibility and osteogenesis were detected by related assays. Additionally, the autophagy signaling pathway was analyzed by western blotting. Polydopamine-templated hydroxyapatite, in combination with metformin, substantially reduced ROS production and apoptosis, and enhanced proliferation and osteogenic differentiation of hPDLSCs. Enhanced levels of microtubule-associated protein 1 light chain 3 II and Beclin-1 were observed after exposure to tHA plus metformin. Expression of phosphorylated AMPK was increased and that of phosphorylated mammalian target of rapamycin (mTOR) was decreased after exposure to tHA plus metformin. Taken together, our results demonstrate that tHA, combined with metformin, increases the viability of hPDLSCs via the AMPK/mTOR signaling pathway by regulating autophagy and further improving the osteogenic effect.

CAS / MDL: 1185-53-1
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Toxics · 2023 ·Vol. 11 ·期 12 ·992 · IF 4.6

Proteomic Analysis of the Mitochondrial Responses in P19 Embryonic Stem Cells Exposed to Florfenicol

Zhihua Dong,Xueke Hou,Xueying Wang,Zihui Shen,Huiqing Pang,Lingli Chen,Zhihong Yin,Fei Ren,Weiguo Li,Yaming Ge,Hongmei Ning,Dongfang Hu

Florfenicol (FLO) has been shown to elicit diverse toxic effects in plants, insects, and mammals. Previously, our investigations revealed that FLO induced abnormal cardiac development and early embryonic mortality in chicken embryos. However, the effect of FLO on mitochondrial responses in stem cells remains unclear. In this study, we show that FLO significantly diminishes proliferation viability and obstructs the directed differentiation of P19 stem cells (P19SCs) into cardiomyocytes. Proteomic analysis revealed 148 differentially expressed proteins in response to FLO. Functional analysis has pinpointed FLO interference with biological processes associated with oxidative phosphorylation within the mitochondria. In alignment with the results of proteomic analysis, we confirmed that FLO inhibits the expression of both nuclear DNA-encoded and mitochondrial DNA-encoded subunits of the electron transport chain. Subsequent experiments demonstrated that FLO disrupts mitochondrial dynamics and induces the mitochondrial unfolded protein response to maintain mitochondrial homeostasis. These findings collectively highlight the significance of mitochondrial dynamics and the mitochondrial unfolded protein response to mediate the decreased proliferation viability and directed differentiation potential in P19SCs treated with FLO. In conclusion, this study provides a comprehensive overview of mitochondrial responses to FLO-induced cytotoxicity and enhances our understandings of the molecular mechanisms underlying FLO-induced embryonic toxicity.Keywords:florfenicol;proteomic analysis;mitochondrial dynamics;embryonic toxicity

✓ 已验证 DOI PubMed 高影响因子
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COMPOSITES PART B-ENGINEERING · 2018 · IF 4.92

Extraction and characterization of cellulose nanofibers and nanocrystals from liquefied banana pseudo-stem residue

Fanrong Meng,Guoqing Wang,Xueyu Du,Zhifen Wang,Shuying Xu,Yucang Zhang

Banana pseudo-stems fibers were novel extracted via atmospheric liquefaction combined with TEMPO-mediated oxidation . Cellulose nanofibers (CNF) and nanocrystals (CNC) were subsequently obtained by high-intensity ultrasonic treatment and acidolysis, respectively. Liquefied residue content as well as its constituent varied with liquefaction time. Scanning electron microscopy and fourier transform infrared demonstrate that the progressive removal of non-cellulosic impurities. Morphological studies exhibit that CNF present a range of 3∼10 nm in diameter and 140∼690 nm in length, while CNC have average diameter of 3.5 ± 1.6 nm and a length of 93.3 ± 37.6 nm. XRD analysis indicates that the CNCs have a high crystallinity (95.6%). The thermal stability of the fibers was measured by thermogravimetric analysis . The structures and properties of CNF and CNC give it potential to be used in reinforcing polymeric matrix materials .

CAS / MDL: 7758-19-2 2564-83-2
研究领域: 材料科学 · 植物资源利用
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A · 2018 ·Vol. 106 ·期 11 ·2973-2983 · IF 3.231

Enhancing neural differentiation of induced pluripotent stem cells by conductive graphene/silk fibroin films

Yimeng Niu,Xiaofang Chen,Danyu Yao,Ge Peng,Haifeng Liu,Yubo Fan

Nerve regeneration and function recovery remain challenges for tissue engineering. The application of suitable scaffold in tissue engineering has been demonstrated to be able to enhance nerve regeneration and differentiation. However, a desired scaffold must meet the requirements of good cytocompatibility and high electrical conductivity simultaneously. In this study, a conductive film composed of SF and graphene was successfully fabricated, which was applied to evaluate its effect on the neural differentiation of iPSCs. The conductive film was found to enhance the differentiation of iPSCs toward neurons. In addition, the differentiation was enhanced with graphene contents and highest value was obtained at graphene content of 4%. Thus, the results in this study suggested that 4% G/SF film might be a suitable biomaterial scaffold for application in neural regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2973–2983, 2018.

CAS / MDL: 7550-35-8
研究领域: 组织工程 · 神经科学 · 生物材料
✓ 已验证 产品关联 DOI PubMed 高影响因子
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