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Materials Science & Engineering C-Materials for Biological Applications · 2020 · IF 5.88

Oxidized starch cross-linked porous collagen-based hydrogel for spontaneous agglomeration growth of adipose-derived stem cells

Xiaofen Xie,Xinying Li,Jinfeng Lei,Xi Zhao,Yongbo Lyu,Changdao Mu,Defu Li,Liming Ge,Yongbin Xu

Many strategies have been employed to artificially reconstruct adipose tissue in tissue engineering. The functionalization and survival of reconstructed adipose tissue depend on sufficient angiogenesis. Notably, agglomeration growth of adipose-derived stem cells (ASCs) is beneficial to promoting angiogenesis. Herein, we present a porous collagen-based hydrogel for spontaneous agglomeration growth of ASCs to promote angiogenesis. Oxidized starch with different oxidation degree was prepared and used to cross-link collagen to fabricate the porous hydrogel. The gelation time and pore size of hydrogels can be controlled by adjusting the oxidation degree of starch. Crosslinking enhances the mechanical properties, inhibits the swelling and biodegradation of the hydrogels. The hydrogels possess good blood compatibility and cytocompatibility. Significantly, ASCs tended to adhere to the hydrogels and spontaneously grew into spheres along with time. Effective expression of vascular endothelial growth and fibroblast growth factors were observed. Overall, the hydrogels have application prospects in vascularized adipose tissue engineering.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF NANOPARTICLE RESEARCH · 2021 ·Vol. 23 ·期 7 ·1-14 · IF 2.253

La(OH)3 nanorods with different sizes enhanced osteogenic differentiation on mice bone marrow mesenchymal stem cells

Yu Linkang,Lin Runlian,Han Yu,Fan Dehui,Zhou Guoqiang,Zhang Jinchao,Jia Guang,Ge Kun

With the wide use of rare earth nanomaterials in industry, environmental control, and medicine with their unique properties, it has focused on the exposure of humans to the rare earth nanoparticles in recent years. Because of the similar properties of rare earth and calcium, rare earth nanoparticles can deposit in the bone and affect the osteogenic differentiation of bone mesenchymal stem cells (BMSCs). La(OH) 3 nanoparticles are widely used in the catalysis, sensor, electrode, and luminescent materials. However, there are few reports about the bioactivity of La(OH) 3 nanoparticles on the bone metabolism. In this work, three La(OH) 3 nanorods have been got by hydrothermal method, Long-, Medium-, and Short-La(OH) 3 nanorods, the lengths of which were of ~ 640, 255, and 80 nm, and the diameters of which were of ~ 85, 40, and 35 nm, respectively. All the La(OH) 3 nanorods showed no effect on BMSCs viability and the blood compatibility. But the osteogenic differentiation showed a significant difference in La(OH) 3 nanorods, in which Short-La(OH) 3 nanorods showed the highest promoting effect on osteogenic differentiation. The potential mechanism in the osteogenic differentiation caused by three La(OH) 3 nanorods was correlated with the different uptake efficiency in BMSCs and degradation in lysosome to form LaPO 4 . This work on La(OH) 3 nanorods provides the basic data for the development of lanthanum-based nanoparticles. Graphical abstract

CAS / MDL: 7803-57-8 1312-81-8
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Experimental and Therapeutic Medicine · 2021 ·Vol. 22 ·期 5 ·1-12 · IF 2.447

Autophagy is involved in neurofibromatosis type I gene‑modulated osteogenic differentiation in human bone mesenchymal stem cells

Yiqiang Li,Mingwei Zhu,Xuemei Lin,Jingchun Li,Zhe Yuan,Yanhan Liu,Hongwen Xu

Neurofibromatosis type I (NF1) is an autosomal dominant genetic disease that is caused by mutations in the NF1 gene. Various studies have previously demonstrated that the mTOR complex 1 signaling pathway is essential for the NF1‑modulated osteogenic differentiation of bone mesenchymal stem cells (BMSCs). Additionally, the mTOR signaling pathway plays a notable role in autophagy. The present study hypothesized that NF1 could modulate the osteogenic differentiation of BMSCs by regulating the autophagic activities of BMSCs. In the present study, human BMSCs were cultured in an osteogenic induction medium. The expression of the NF1 gene was either knocked down or overexpressed by transfection with a specific small interfering RNA (siRNA) targeting NF1 or the pcDNA3.0 NF1‑overexpression plasmid, respectively. Autophagic activities of BMSCs (Beclin‑1, P62, LC3B I, and LC3B II) were determined using western blotting, electron microscopy, acridine orange (AO) staining and autophagic flux/lysosomal detection by fluorescence microscopy. In addition, the autophagy activator rapamycin (RAPA) and inhibitor 3‑methyladenine (3‑MA) were used to investigate the effects of autophagy on NF1‑modulated osteogenic differentiation in BMSCs. Inhibiting NF1 with siRNA significantly decreased the expression levels of autophagy markers Beclin‑1 and LC3B‑II, in addition to osteogenic differentiation markers osterix, runt‑related transcription factor 2 and alkaline phosphatase. By contrast, overexpressing NF1 with pcDNA3.0 significantly increased their levels. Transmission electron microscopy, AO staining and autophagic flux/lysosomal detection assays revealed that the extent of autophagosome formation was significantly decreased in the NF1‑siRNA group but significantly increased in the NF1‑pcDNA3.0 group when compared with the NC‑siRNA and pcDNA3.0 groups, respectively. In addition, the activity of the PI3K/AKT/mTOR pathway [phosphorylated (p)‑PI3K, p‑AKT, p‑mTOR and p‑p70S6 kinase] was significantly upregulated in the NF1‑siRNA group compared with the NC‑siRNA group, and significantly inhibited in the NF1‑pcDNA3.0 group, compared with the pcDNA3.0 group. The knockdown effects of NF1‑siRNA on the autophagy and osteogenic differentiation of BMSCs were reversed by the autophagy activator RAPA, while the overexpression effects of NF1‑pcDNA3.0 on the autophagy and osteogenic differentiation of BMSCs were reversed by the autophagy inhibitor 3‑MA. In conclusion, results from the present study suggest at the involvement of autophagy in the NF1‑modulated osteogenic differentiation of BMSCs. Furthermore, NF1 may partially regulate the autophagic activity of BMSCs through the PI3K/AKT/mTOR signaling pathway.

CAS / MDL: 50-81-7 50-02-2
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ACS Biomaterials Science & Engineering · 2019 · IF 4.511

Fabrication and Characterization of Pectin Hydrogel Nanofiber Scaffolds for Differentiation of Mesenchymal Stem Cells into Vascular Cells

Na Li,Fuxin Xue,Hui Zhang,Hanna J. Sanyour,Alex P. Rickel,Andrew Uttecht,Betty Fanta,Junli Hu,Zhongkui Hong

Despite significant progress over the past few decades, creating a tissue-engineered vascular graft with replicated functions of native blood vessels remains a challenge due to the mismatch in mechanical properties, low biological function, and rapid occlusion caused by restenosis of small diameter vessel grafts (<6 mm diameter). A scaffold with similar mechanical properties and biocompatibility to the host tissue is ideally needed for the attachment and proliferation of cells to support the building of engineered tissue. In this study, pectin hydrogel nanofiber scaffolds with two different oxidation degrees (25 and 50%) were prepared by a multistep methodology including periodate oxidation, electrospinning, and adipic acid dihydrazide crosslinking. Scanning electron microscopy (SEM) images showed that the obtained pectin nanofiber mats have a nano-sized fibrous structure with 300–400 nm fiber diameter. Physicochemical property testing using Fourier transform infrared (FTIR) spectra, atomic force microscopy (AFM) nanoindentations, and contact angle measurements demonstrated that the stiffness and hydrophobicity of the fiber mat could be manipulated by adjusting the oxidation and crosslinking levels of the pectin hydrogels. Live/Dead staining showed high viability of the mesenchymal stem cells (MSCs) cultured on the pectin hydrogel fiber scaffold for 14 days. In addition, the potential application of pectin hydrogel nanofiber scaffolds of different stiffness in stem cell differentiation into vascular cells was assessed by gene expression analysis. Real-time polymerase chain reaction (RT-PCR) results showed that the stiffer scaffold facilitated the differentiation of MSCs into vascular smooth muscle cells, while the softer fiber mat promoted MSC differentiation into endothelial cells. Altogether, our results indicate that the pectin hydrogel nanofibers have the capability of providing mechanical cues that induce MSC differentiation into vascular cells and can be potentially applied in stem cell-based tissue engineering.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Biomaterials Science · 2019 ·Vol. 7 ·期 5 ·1973-1983 · IF 5.251

Zein/gelatin/nanohydroxyapatite nanofibrous scaffolds are biocompatible and promote osteogenic differentiation of human periodontal ligament stem cells

Qianmin Ou,Yingling Miao,Fanqiao Yang,Xuefeng Lin,Li-Ming Zhang,Yan Wang

In bone tissue engineering, it is important for biomaterials to promote the osteogenic differentiation of stem cells to achieve tissue regeneration. Therefore, it is critical to develop biomaterials with excellent cytocompatibility and osteoinductive ability. In our previous study, we found a zein/gelatin electrospinning scaffold with good biocompatibility, but low osteoinductive ability for human periodontal ligament stem cells (hPDLSCs). Therefore, herein, we fabricated novel zein/gelatin/nanohydroxyapatite (zein/gelatin/nHAp) nanofibrous membranes to overcome the drawbacks of the zein/gelatin scaffold. The results showed that the surface wettability of the zein/gelatin/nHAp nanofiber membranes was increased. Moreover, the inclusion of nHAp facilitated the attachment, proliferation, and osteogenic differentiation of hPDLSCs. Overall, the zein/gelatin/nHAp nanofiber membranes showed good biocompatibility and osteoinductive activity for hPDLSCs in vitro and in vivo; this suggested potential applications of these membranes in bone tissue engineering.

✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A · 2019 ·Vol. 107 ·期 11 ·2414-2424 · IF 3.221

Citric acid modification of a polymer exhibits antioxidant and anti-inflammatory properties in stem cells and tissues

Xiaopei Wu,Honglian Dai,Chao Xu,Langlang Liu,Shipu Li

Biomaterials can be used as carriers of antioxidant or drug to the oxidative injury site of tissue and decrease intracellular oxidative stress levels, however, low dosage delivery or unstable molecular structure of antioxidant or drug limited the long-term sustained release. A chemically stable antioxidant molecule is essential to serve as antioxidant structure components of biomaterials that may provide the relatively high antioxidant content and persisting local antioxidant release with the degradation of materials. In this study, we used citric acid modified polyvinyl alcohol (PVA-C) as a model biomaterial to investigate the role of citric acid on the material stimulated antioxidant and anti-inflammatory effects. In cellular-based assays, PVA-C extracts showed a protective effects on bone marrow mesenchymal stem cells (BMSCs) under oxidative stress. It could enhance the antiapoptotic ability of stem cells by inhibiting reactive oxygen species. Further studies revealed that PVA-C extracts upregulated the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) and superoxide dismutase [Mn] (SOD2). in vivo animal assays, PVA-C extracts showed significant inhibitory effects on the oxidative stress and inflammatory reaction which were induced by lipopolysaccharide (LPS). These findings suggest that the citric acid modified polymer can regulate the redox signaling of stem cells and tissues by the release of citric acid from materials, leading to enhanced oxidative stress-induced degenerative diseases and inflammatory diseases therapy.

CAS / MDL: 9002-89-5
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ACS Biomaterials Science & Engineering · 2018 · IF 4.432

Codelivery of Synovium-Derived Mesenchymal Stem Cells and TGF-β by a Hybrid Scaffold for Cartilage Regeneration

Hongjie Huang,Xiaoqing Hu,Xin Zhang,Xiaoning Duan,Jiying Zhang,Xin Fu,Linghui Dai,Lan Yuan,Chunyan Zhou,Yingfang Ao

Synovium-derived mesenchymal stem cells (SMSCs) are attractive tissue-specific cells for cartilage regeneration because of their easy availability, higher chondrogenic potential, and joint specificity. In the present study, we established a hybrid scaffold to codeliver SMSCs and transforming growth factor beta (TGF-β), which can integrate the scaffolds, the growth factor, and the autogenous cells within rabbit cartilage defects. A chitosan hydrogel and a decellularized bone matrix were used to fabricate the gel–solid duplex phase biomaterials, which were proven to retain more cells, promote tissue integration, and provide mechanical support. In vitro experiments demonstrated that this hybrid scaffold could release TGF-β in a controlled biphasic pattern, which can promote cell proliferation and chondrogenic differentiation of loaded rabbit SMSCs. For in vivo experiments, we filled cartilage defects with the hybrid materials, delivering autogenous SMSCs and TGF-β simultaneously via chitosan’s sol–gel transition. Histological analysis, magnetic resonance imaging, and nanoindentation assessment indicated superior cartilage regeneration using this codelivery system compared with that from routine microfracture or control delivery scaffolds. Beyond cartilage regeneration, the easy preparation, favorable biophysical properties, and controlled release ability make this codelivery system applicable to transport other tissue-specific cells or biofactors for tissue engineering.

CAS / MDL: 9012-76-4
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PHARMAZIE · 2018 ·Vol. 73 ·期 12 ·729-732 · IF 1.016

Retinoic acid increases the anticancer effect of paclitaxel by inducing differentiation of cancer stem cells in melanoma

Wang YB.,Sun B.,Han B.

Malignant melanoma is a highly lethal disease, and advanced stages of melanoma have proven to be resistant to many chemotherapeutic drugs including temozolomide and paclitaxel. Cancer stem cells (CSCs) have been identified and isolated in different cancers including melanoma, and have been proven playing important role in the drug resistance. Retinoic acid (RA) is a promising anticancer agent, which can induce differentiation of CSCs. The main purpose of the present study was to evaluate the possible RA-induced differentiation of melanoma CSCs and sensitization of melanoma CSCs to paclitaxel. Our results show that CSCs of human melanoma A375 cells was more tolerant to paclitaxel than other non-CSCs melanoma cells. On the contrary, RA had stronger inhibitory effect on melanoma CSCs than on non-CSCs. At the same time, RA could arrest the cell cycle of CSCs and reduce the expression of Sox-2, Oct-4 in CSCs of melanoma, thereby induced the differentiation of CSCs and increased its sensitivity to paclitaxel. With this study we concluded that RA increases the anticancer effect of paclitaxel by inducing differentiation of cancer stem cells in melanoma, and the combined application of RA and paclitaxel may be more effective in the treatment of melanoma.

CAS / MDL: 67-68-5 298-93-1
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PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES · 2018 ·Vol. 285 ·期 1883 · IF 4.847

Bt rice plants may protect neighbouring non-Bt rice plants against the striped stem borer, Chilo suppressalis

Yaoyu Jiao,Xiaoyun Hu,Yufa Peng,Kongming Wu,Jörg Romeis,Yunhe Li

The area planted with insect-resistant genetically engineered crops expressing Bacillus thuringiensis (Bt) genes has greatly increased in many areas of the world. Given the nearby presence of non-Bt crops (including those planted as refuges) and non-crop habitats, pests targeted by the Bt trait have a choice between Bt and non-Bt crops or weeds, and their host preference may greatly affect insect management and management of pest resistance to Bt proteins. In this study, we examined the oviposition preference of the target pest of Bt rice, Chilo suppressalis, for Bt versus non-Bt rice plants as influenced by previous damage caused by C. suppressalis larvae. The results showed that C. suppressalis females had no oviposition preference for undamaged Bt or non-Bt plants but were repelled by conspecific-damaged plants whether Bt or non-Bt. Consequently, C. suppressalis egg masses were more numerous on Bt plants than on neighbouring non-Bt plants both in greenhouse and in field experiments due to the significantly greater caterpillar damage on non-Bt plants. We also found evidence of poorer performance of C. suppressalis larvae on conspecific-damaged rice plants when compared with undamaged plants. GC-MS analyses showed that larval damage induced the release of volatiles that repelled mated C. suppressalis females in wind tunnel experiments. These findings suggest that Bt rice could act as a dead-end trap crop for C. suppressalis and thereby protect adjacent non-Bt rice plants. The results also indicate that the oviposition behaviour of target pest females should be considered in the development of Bt resistance management strategies.

CAS / MDL: 821-55-6
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Biomedical Materials · 2014 ·Vol. 9 ·期 3 ·035008 · IF 2.922

Directing chondrogenic differentiation of mesenchymal stem cells with a solid-supported chitosan thermogel for cartilage tissue engineering

Hongjie Huang,Xin Zhang,Xiaoqing Hu,Linghui Dai,Jingxian Zhu,Zhentao Man,Haifeng Chen,Chunyan Zhou,Yingfang Ao

Hydrogels are attractive for cartilage tissue engineering because of their high plasticity and similarity with the native cartilage matrix. However, one critical drawback of hydrogels for osteochondral repair is their inadequate mechanical strength. To address this limitation, we constructed a solid-supported thermogel comprising a chitosan hydrogel system and demineralized bone matrix. Scanning electron microscopy, the equilibrium scanning ratio, the biodegradation rate, biomechanical tests, biochemical assays, metabolic activity tests, immunostaining and cartilage-specific gene expression analysis were used to evaluate the solid-supported thermogel. Compared with pure hydrogel or demineralized matrix, the hybrid biomaterial showed superior porosity, equilibrium swelling and degradation rate. The hybrid scaffolds exhibited an increased mechanical strength: 75% and 30% higher compared with pure hydrogels and demineralized matrix, respectively. After three days culture, bone-derived mesenchymal stem cells (BMSCs) maintained viability above 90% in all three materials; however, the cell retention of the hybrid scaffolds was more efficient and uniform than the other materials. Matrix production and chondrogenic differentiation of BMSCs in the hybrid scaffolds were superior to its precursors, based on glycosaminoglycan quantification and hyaline cartilage marker expression after three weeks in culture. Its easy preparation, favourable biophysical properties and chondrogenic capacity indicated that this solid-supported thermogel could be an attractive biomaterial framework for cartilage tissue engineering.

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Stem Cell Research & Therapy · 2017 ·Vol. 8 ·期 1 ·1-13 · IF 4.211

Using low-risk factors to generate non-integrated human induced pluripotent stem cells from urine-derived cells

Wang Linli,Chen Yuehua,Guan Chunyan,Zhao Zhiju,Li Qiang,Yang Jianguo,Mo Jian,Wang Bin,Wu Wei,Yang Xiaohui,Song Libing,Li Jun

Background Because the lack of an induced pluripotent stem cell (iPSC) induction system with optimal safety and efficiency limits the application of these cells, development of such a system is important.Methods To create such an induction system, we screened a variety of reprogrammed plasmid combinations and multiple compounds and then verified the system’s feasibility using urine cells from different individuals. We also compared large-scale iPSC chromosomal variations and expression of genes associated with genomic stability between this system and the traditional episomal system using karyotype and quantitative reverse transcription polymerase chain reaction analyses.Results We developed a high-efficiency episomal system, the 6F/BM1-4C system, lacking tumorigenic factors for human urine-derived cell (hUC) reprogramming. This system includes six low-risk factors (6F), Oct4, Glis1, Klf4, Sox2, L-Myc, and the miR-302 cluster. Transfected hUCs were treated with four compounds (4C), inhibitor of lysine-demethylase1, methyl ethyl ketone, glycogen synthase kinase 3 beta, and histone deacetylase, within a short time period. Comparative analysis revealed significantly decreased chromosomal variation in iPSCs and significantly increased Sirt1 expression compared with iPSCs induced using the traditional episomal system.Conclusion The 6F/BM1-4C system effectively induces reprogramming of urine cells in samples obtained from different individuals. iPSCs induced using the 6F/BM1-4C system are more stable at the cytogenetic level and have potential value for clinical application.

CAS / MDL: 298-83-9
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Chemistry Central Journal · 2017 ·Vol. 11 ·期 1 ·1-8 · IF 2.442

Two phenolic antioxidants in Suoyang enhance viability of •OH-damaged mesenchymal stem cells: comparison and mechanistic chemistry

Xie Yulu,Li Xican,Xu Jieying,Jiang Qian,Xie Hong,He Jianfeng,Chen Dongfeng

Background Suoyang originates from a psammophyte named Cynomorium songaricum Rupr and has been known as a phenolic-antioxidant-enriched traditional Chinese herbal medicine. The present study attempted to investigate the protective effect of phenolic antioxidants in Suoyang towards •OH-mediated MSCs and then further discusses the chemical mechanisms.Methods The lyophilized aqueous extract of Suoyang (LAS) was prepared and characterized using HPLC. Then, two phenolic antioxidant references, epicatechin and luteolin-7-O-β-D-glucoside, along with LAS, were investigated for their effects on the viability of •OH-treated MSCs using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay. The comparison and mechanistic chemistry of epicatechin and luteolin-7-O-β-D-glucoside were further explored using various antioxidant assays, including PTIO•-scavenging, FRAP (ferric ion reducing antioxidant power), ABTS+•-scavenging, and DPPH•-scavenging. Their Fe2+-binding capacities were also compared using ultraviolet (UV) spectra.Results The HPLC analysis indicated that there are 8 phenolic antioxidants in LAS, including epicatechin, luteolin-7-O-β-D-glucoside, gallic acid, protocatechuic acid, catechin, isoquercitrin, phlorizin, and naringenin. The MTT assay revealed that epicatechin could more effectively increase the survival of •OH-treated MSCs than luteolin-7-O-β-D-glucoside. Similarly, epicatechin exhibited higher antioxidant abilities than luteolin-7-O-β-D-glucoside in the DPPH•-scavenging, ABTS+•-scavenging, FRAP, and PTIO•-scavenging assays. In the Fe2+-binding assay, luteolin-7-O-β-D-glucoside gave a stronger UV peak at 600 nm, with ε = 2.62 × 106 M−1 cm−1, while epicatechin produced two peaks at 450 nm (ε = 8.47 × 105 M−1 cm−1) and 750 nm (ε = 9.68 × 105 M−1 cm−1).Conclusion As two reference antioxidants in Suoyang, epicatechin and luteolin-7-O-β-D-glucoside can enhance the viability of •OH-damaged MSCs. Such a beneficial effect may be from their antioxidant effects, including direct-antioxidant and indirect-antioxidant (i.e., Fe2+-binding) processes. In the direct-antioxidant process, proton (H+), one electron (e), or even hydrogen-atom (•H) transfer may occur to fulfill radical-scavenging (especially •OH-scavenging); in this aspect, epicatechin is superior to luteolin-7-O-β-D-glucoside due to the presence of more phenolic –OHs. The additional –OHs can also be responsible for the better cytoprotective effect. In terms of indirect-antioxidant potential, however, epicatechin is inferior to luteolin-7-O-β-D-glucoside due to the absence of a hydroxyl-keto moiety. These findings will provide new information about medicinal psammophytes for MSC transplantation.

CAS / MDL: 149-91-7
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