Journal of Biomaterials and Tissue Engineering
·
2020
·Vol. 10
·期 6
·812-822
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IF 0.511
Bai Yi-Hua,Yang Min,Wang Jia-Ping,Jiang Hong-Ying,Li Luo-Hua,Zhang Xin-Xin,Ma Li
The present study aims to probe the impact of mesenchymal stem cells (MSCs) on the HMGA2 gene and renal tubular epithelial cell EMT in diabetic nephropathy (DN). The advanced glycation end product (AGE) in the later period was used to interfere with the HK-2 cell modeling of humans
in vitro, while STZ was used for the modeling of mice DN in vivo. Allogeneic MSCs were used to interfere with the model to detect the concentration of the correlation factor in cells and mice kidney tissues and HMGA2 expression level. The following aspects were prompted after
treatment with MSCs in vitro and in vivo: (1) TGF-β1 concentration, Smad2, HMGA2, vimentin and α-SMA expression levels were significantly reduced, when compared to the model group (P <0.05), while Smad7 and E-cadherin expression levels significantly
increased, when compared to the model group (P <0.05); (2) The proteinuria and serum creatinine level of mice were alleviated, and the ultrastructure damage condition of kidneys also improved, when compared to the model group. MSCs can restrain the high expression of HMGA2 in DN,
EMT and kidney fibrosis, and postpone renal function progression.
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Biomaterials Science
·
2018
·Vol. 6
·期 10
·2738-2749
·
IF 5.831
Weijun Zhang,Kunxi Zhang,Guifei Li,Shifeng Yan,Lei Cui,Jingbo Yin
Shape memory scaffolds are minimally invasive cell carriers that are promising biomaterials for tissue regeneration. Since cell fate is critical for successful regeneration, the influence of mechanostructural stimuli induced by shape memory on cell fate is worthy of investigation. In this study, we developed a poly(L-glutamic acid)-based (PLGA-based) shape memory porous scaffold by cross-linking PLGA with poly(ε-caprolactone)-diols (PCL-diols) and by using the particle leaching method. After regulating the cross-linking density and molecular weight of the PCL-diols, the scaffolds exhibited excellent shape memory properties around physiological temperatures. The interconnected porous structure not only enabled the scaffold to be deformed to 20% of its original size but also supported tissue invasion. In vivo results demonstrated that the PLGA-based scaffold degraded within 6 months. Cell fate studies indicated that large dimensional deformation of the porous structure during the shape memory process induced significant death, detachment and reorganization of stem cells but had negligible effects on stemness and proliferation. These results indicate that the PLGA-based shape memory porous scaffold is a potential cell carrier for tissue regeneration, and they are also meaningful to investigate the effects of mechanostructural stimuli on stem cell fate in porous structures.
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Stem Cell Research & Therapy
·
2021
·Vol. 12
·期 1
·1-15
·
IF 6.832
Ma Yinzhong,Wang Lisha,Yang Shilun,Liu Dongyu,Zeng Yi,Lin Lilong,Qiu Linhui,Lu Jiahao,Chang Junlei,Li Zhihuan
Background The therapeutic efficacy of mesenchymal stem cells (MSCs) of different tissue origins on metabolic disorders can be varied in many ways but remains poorly defined. Here we report a comprehensive comparison of human MSCs derived from umbilical cord Wharton’s jelly (UC-MSCs), dental pulp (PU-MSCs), and adipose tissue (AD-MSCs) on the treatment of glucose and lipid metabolic disorders in type II diabetic mice.Methods Fourteen-to-fifteen-week-old male C57BL/6 db/db mice were intravenously administered with human UC-MSCs, PU-MSCs, and AD-MSCs at various doses or vehicle control once every 2 weeks for 6 weeks. Metformin (MET) was given orally to animals in a separate group once a day at weeks 4 to 6 as a positive control. Body weight, blood glucose, and insulin levels were measured every week. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were performed every 2 weeks. All the animals were sacrificed at week 6 and the blood and liver tissues were collected for biochemical and histological examinations.Results UC-MSCs showed the strongest efficacy in reducing fasting glucose levels, increasing fasting insulin levels, and improving GTT and ITT in a dose-dependent manner, whereas PU-MSCs showed an intermediate efficacy and AD-MSCs showed the least efficacy on these parameters. Moreover, UC-MSCs also reduced the serum low-density lipoprotein cholesterol (LDL-C) levels with the most prominent potency and AD-MSCs had only very weak effect on LDL-C. In contrast, AD-MSCs substantially reduced the lipid content and histological lesion of liver and accompanying biomarkers of liver injury such as serum aspartate transaminase (AST) and alanine aminotransferase (ALT) levels, whereas UC-MSCs and PU-MSCs displayed no or modest effects on these parameters, respectively.Conclusion sTaken together, our results demonstrated that MSCs of different tissue origins can confer substantially different therapeutic efficacy in ameliorating glucose and lipid metabolic disorders in type II diabetes. MSCs with different therapeutic characteristics could be selected according to the purpose of the treatment in the future clinical practice.
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FOOD CHEMISTRY
·
2024
·
IF 8.5
Xueyin Ru,Wanli You,Jinglin Zhang,Feng Xu,Zhengguo Wu,Peng Jin,Yonghua Zheng,Shifeng Cao
The effects of γ-aminobutyric (GABA) on enzymatic browning , storage quality, membrane and reactive oxygen species (ROS) metabolism in fresh-cut stem lettuce were investigated. The results illustrated that GABA treatment delayed browning degree, polyphenol oxidase (PPO) activity and the expression of LsPPO . Meanwhile, higher chlorophyll and ascorbic acid contents were exhibited in GABA-treated stem lettuce, as well as the slower microbial propagation. Further investigation revealed that exogenous GABA application declined malondialdehyde content, electrolyte leakage and the enzyme activities of membrane metabolism, and the expression levels of related genes were also downregulated. In addition, GABA treatment scavenged ROS and strengthened the enzyme activities of ROS metabolism, as well as the expression levels of corresponding genes. Taken together, these findings implied that the repressed enzymatic browning and microbial propagation in GABA-treated stem lettuce were due to the inhibition of ROS accumulation, enhancement of membrane stability and increased resistance to oxidation .
研究领域:
食品科学
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植物生理学
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采后技术
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CELLULAR AND MOLECULAR LIFE SCIENCES
·
2026
·Vol. 83
·期 1
·219
·
IF 6.5
Fan Xinxin,Yan Jinhua,Yuan Yu,Chen Yi,Chen Haiyang
The global incidence of inflammatory bowel disease (IBD) is rising, an epidemiological trend strongly linked to the increasing consumption of ultra-processed foods. Although certain food additives are implicated in IBD pathogenesis, the direct impact of these additives on intestinal stem cells (ISCs), key effectors of epithelial homeostasis and repair, is poorly defined. Specifically, 4-hexylresorcinol (4-HR), a widely used phenolic preservative, has not been thoroughly investigated for its long-term impact on intestinal health, particularly during inflammation and repair. Using a Drosophila melanogaster model of bleomycin (BLM)-induced intestinal injury, we combined genetic analysis, immunofluorescence staining, and functional assays to evaluate the effects of 4-HR on tissue pathology, ISC proliferation, and evolutionarily conserved pro-repair signaling pathways. Our findings indicate that 4-HR significantly aggravates intestinal damage and impedes epithelial regeneration by suppressing the injury-induced proliferation of ISCs. Mechanistic studies revealed that 4-HR inhibits the activation of the MAPK signaling pathway, which is critical for initiating the reparative program following injury. Importantly, we extend these findings to a mammalian system, demonstrating that 4-HR similarly impairs intestinal repair and suppresses the conserved MAPK signaling axis in a mouse model of colitis. Collectively, our data elucidate a previously unrecognized mechanism whereby the food additive 4-HR aggravates intestinal damage and impedes epithelial regeneration by directly suppression MAPK-dependent, ISC-driven repair. This cross-species validation establishes the detrimental role of 4-HR and its core mechanism as conserved from invertebrates to mammals, not only establishing a novel link between dietary factors and epithelial repair dysregulation but also underscoring a significant dietary environmental contributor to IBD pathogenesis. Furthermore, this study establishes a foundation for future research into how dietary components influence stem-cell biology, underscoring the urgent need to re-evaluate the long-term safety of common food additives in vulnerable populations.
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Biofabrication
·
2025
·Vol. 18
·期 1
·015010
·
IF 8
Xuan Jiao,Kexun Liu,Jie Wu,Peian Cai,Limeng Chao,Chang Liu,Kegong Chen,Xionghai Qin,Xin Tian,Yuanzhong Zhao,Hai Tian,Wei Chen
The transplantation of human bone marrow mesenchymal stem cells (hMSCs) exhibits promising therapeutic effects in the treatment of myocardial infarction (MI), however, its clinical application is limited due to the low survival rate of the transplanted cells. Three-dimensional (3D) bioprinted tissue engineering patches have demonstrated efficacy as a delivery approach to enhance the viability and engraftment of stem cells. In this study, we have developed a novel hMSCs tissue-engineered patch equipped with a nano-slow-release system using 3D bioprinting technology. The patch is based on a matrix material consisting of methacrylated gelatin (GelMA) and chitosan nanoparticles loaded with vascular endothelial growth factor (VEGF), which possesses pro-angiogenic effects. The resulting patch demonstrated excellent compatibility with hMSCs and enabled stable, sustained VEGF release. In vivo results showed that the patch significantly reduced cardiomyocyte apoptosis three days after MI, and improved cardiac function and myocardial fibrosis at 28 d post-surgery. These effects were closely associated with the patch’s potent angiogenic properties and favorable stem cell survival. In conclusion, this study successfully developed a 3D-printed tissue engineering patch with strong potential for clinical application, offering a promising new approach for the treatment of MI.
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International Journal of Oral Science
·
2024
·Vol. 16
·期 1
·1-16
·
IF 10.8
Chen Jiayao,Kuang Shuhong,Cen Jietao,Zhang Yong,Shen Zongshan,Qin Wei,Huang Qiting,Wang Zifeng,Gao Xianling,Huang Fang,Lin Zhengmei
The consumption of a high-fat diet (HFD) has been linked to osteoporosis and an increased risk of fragility fractures. However, the specific mechanisms of HFD-induced osteoporosis are not fully understood. Our study shows that exposure to an HFD induces premature senescence in bone marrow mesenchymal stem cells (BMSCs), diminishing their proliferation and osteogenic capability, and thereby contributes to osteoporosis. Transcriptomic and chromatin accessibility analyses revealed the decreased chromatin accessibility of vitamin D receptor (VDR)-binding sequences and decreased VDR signaling in BMSCs from HFD-fed mice, suggesting that VDR is a key regulator of BMSC senescence. Notably, the administration of a VDR activator to HFD-fed mice rescued BMSC senescence and significantly improved osteogenesis, bone mass, and other bone parameters. Mechanistically, VDR activation reduced BMSC senescence by decreasing intracellular reactive oxygen species (ROS) levels and preserving mitochondrial function. Our findings not only elucidate the mechanisms by which an HFD induces BMSC senescence and associated osteoporosis but also offer new insights into treating HFD-induced osteoporosis by targeting the VDR-superoxide dismutase 2 (SOD2)-ROS axis.
研究领域:
生物学
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生物化学
·
干细胞研究
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营养学
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内分泌学
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老年学
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
·
2022
·Vol. 111
·期 1
·161-172
·
IF 3.405
Xueying Huang,Jie Zeng,Yi Wang
Natural proteins have been reported to positively affect the attachment and proliferation of cells. For the first time, zein, a plant protein, was utilized to make patterned surface mimicking the extracellular matrix to assist the attachment and proliferation of stem cells. Zein would promote the attachment and proliferation of the stem cells more than 10 times of that of gelatin and silk fibroin, respectively, which are popular protein selections for the formation of the biomaterial scaffolds. The more the surface was covered by zein, the more the stem cell grown. It was revealed that the stem cells would grow and stretch in the direction of the patterns, and the stem cells preferred to grow in the grooves in the size of 8 μm, that was similar to the size of the stem cells, rather than the size larger or smaller than that of the cells, such as 50 and 2 μm. It was concluded that zein is a better choice than silk fibroin and gelatin with highly potential for the formation of patterned surface and structure as the biomaterial scaffolds for stem cell therapy.
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Stem Cell Research & Therapy
·
2021
·Vol. 12
·期 1
·1-13
·
IF 6.832
He Qiting,Qin Ruixi,Glowacki Julie,Zhou Shuanhu,Shi Jie,Wang Shaoyi,Gao Yuan,Cheng Lei
Background Vitamin D is important for the mineralization of bones by stimulating osteoblast differentiation of bone marrow mesenchymal stem cells (BMMSCs). BMMSCs are a target of vitamin D action, and the metabolism of 25(OH)D3 to biologically active 1α,25(OH)2D3 in BMMSCs promotes osteoblastogenesis in an autocrine/paracrine manner. Our previous study with human BMMSCs showed that megalin is required for the 25(OH)D3-DBP complex to enter cells and for 25(OH)D3 to stimulate osteoblast differentiation in BMMSCs. Furthermore, we reported that leptin up-regulates megalin in those cells. Leptin is a known inhibitor of PI3K/AKT-dependent chaperone-mediated autophagy (CMA). In this study, we tested the hypothesis that leptin acts synergistically with 25(OH)D3 to promote osteoblastogenesis in rat BMMSCs by a mechanism that entails inhibition of PI3K/AKT-dependent CMA.Methods BMMSCs were isolated from rat bone marrow (4-week-old male SD rats); qRT-PCR and western immunoblots or immunofluorescence were used to evaluate the expression of megalin, ALP, COL1A1, RUNX2, OSX, OSP, and CMA in rBMMSCs. The osteoblast differentiation was evaluated by ALP activity, ALP staining, and calcium deposition. The viability of rBMMSCs was assessed with the CCK-8 kit. Biosynthesis of 1α,25(OH)2D3 was measured by a Rat 1α,25(OH)2D3 ELISA Kit.Results The combination of leptin and 25(OH)D3 treatment significantly enhanced osteoblast differentiation as shown by ALP activity, ALP staining, and calcium deposition, the expression of osteogenic genes ALP, COL1A1, RUNX2, OSX, and OSP by qRT-PCR and western immunoblots in rBMMSCs. Leptin enhanced the expression of megalin and synthesis of 1α,25(OH)2D3 in rBMMSCs. Our data showed that leptin inhibited CMA activity of rBMMSCs by activating PI3K/AKT signal pathway; the ability of leptin to enhance 25(OH)D3 promoted osteoblast differentiation of rBMMSCs was weakened by the PI3K/AKT signal pathway inhibitor.Conclusion sOur data reveal the mechanism by which leptin and 25(OH)D3 promote osteoblast differentiation in rBMMSCs. Leptin promoted the expression of megalin by inhibiting CMA, increased the utilization of 25(OH)D3 by rBMMSCs, and enhanced the ability of 25(OH)D3 to induce osteoblast differentiation of rBMMSCs. PI3K/AKT is at least partially involved in the regulation of CMA. These data indicate the importance of megalin in BMMSCs for vitamin D’s role in skeletal health.
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Acta Biomaterialia
·
2023
·
IF 9.7
Li Meng,Panpan Zhao,Yucheng Jiang,Jiawen You,Zhiyan Xu,Kui Yu,Aldo R. Boccaccini,Kai Zheng,Junqing Ma
Bioactive glass nanoparticles (BGNs) are well-recognized multifunctional biomaterials for bone tissue regeneration due to their capability to stimulate various cellular processes through released biologically active ions. Understanding the correlation between BGN composition and cellular responses is key to developing clinically usable BGN-based medical devices. This study investigated the influence of CaO content of binary SiO 2 -CaO BGNs (CaO ranging from 0 to 10 mol%) on osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and in vivo bone regeneration in zebrafish osteoporosis model. The results showed that BGNs could promote osteogenic differentiation of rBMSCs by indirectly releasing active ions or directly interacting with rBMSCs by internalization. In both situations, BGNs of a higher CaO content could promote the osteogenic differentiation of rBMSCs to a greater extent. The internalized BGNs could activate the transcription factors RUNX2 and OSX, leading to the expression of osteogenesis-related genes. The results in the zebrafish osteoporosis model indicated that the presence of BGNs of higher CaO contents could enhance bone regeneration and rescue dexamethasone-induced osteoporosis to a greater extent. These findings demonstrate that BGNs can stimulate osteogenic differentiation of rBMSCs by releasing active ions or internalization. A higher CaO content facilitates osteogenesis and bone regeneration of zebrafish as well as relieving dexamethasone-induced osteoporosis. The zebrafish osteoporosis model can be a potent tool for evaluating the in vivo bone regeneration effects of bioactive materials. Statement of significance Bioactive glass nanoparticles (BGNs) are increasingly used as fillers of nanocomposites or as delivery platforms of active ions to regenerate bone tissue. Various studies have shown that BGNs can enhance osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by releasing active ions. However, the correlation between BGN composition and cellular responses and in vivo bone regeneration effect has still not been well investigated. Establishment of a suitable in vivo animal model for investigating this correlation is also challenging. The present study reports the influence of CaO content in binary SiO 2 -CaO BGNs on osteogenic differentiation of BMSCs extracellularly and intracellularly. This study also demonstrates the suitability of zebrafish osteoporosis model to investigate in vivo bone regeneration effect of BGNs.
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BIOCHEMICAL PHARMACOLOGY
·
2023
·
IF 5.8
Xuepeng Wang,Chunchun Zou,Changju Hou,Zhenyu Bian,Wu Jiang,Maoqiang Li,Liulong Zhu
Mesenchymal stem cells (MSCs) and their derived extracellular vesicles (EVs) have emerged as promising tools for promoting bone regeneration. This study investigates the functions of EVs derived from bone marrow-derived MSCs (BMSCs) in osteoporosis (OP) and the molecular mechanism. EVs were isolated from primary BMSCs in mice. A mouse model with OP was induced by ovariectomy. Treatment with EVs restored bone mass and strength, attenuated trabecular bone loss and cartilage damage, and increased osteogenesis while suppressing osteoclastogenesis in ovariectomized mice. In vitro , the EVs treatment improved the osteogenic differentiation of MC-3T3 while inhibiting osteoclastic differentiation of RAW264.7 cells. Microarray analysis revealed a significant upregulation of ubiquitin specific peptidase 7 (USP7) expression in mouse bone tissues following EV treatment. USP7 was found to interact with Yes1 associated transcriptional regulator (YAP1) and stabilize YAP1 protein through deubiquitination modification. YAP1-related genes were enriched in the Wnt/β-catenin signaling, and overexpression of YAP1 promoted the nuclear translocation of β-catenin. Functional experiments underscored the critical role of maintaining USP7, YAP1, and β-catenin levels in the pro-osteogenic and anti-osteoclastogenic properties of the BMSC-EVs. In conclusion, this study demonstrates that USP7, delivered by BMSC-derived EVs, stabilizes YAP1 protein, thereby ameliorating bone formation in OP through the Wnt/β-catenin activation.
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Materials Science & Engineering C-Materials for Biological Applications
·
2021
·
IF 7.328
Ying-Zheng Zhao,Rui Chen,Peng-Peng Xue,Lan-Zi Luo,Bin Zhong,Meng-Qi Tong,Bin Chen,Qing Yao,Jian-Dong Yuan,He-Lin Xu
Superparamagnetic iron oxide nanoparticles (SPIONs) have been presented to regulate the migration and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) under magnetic field (MF). However, the toxicity and short residence for the massively exposed SPIONs at bone defects compromises their practical application. Herein, SPIONs were encapsulated into PLGA microspheres to overcome these shortcomings. Three types of PLGA microspheres (PFe-I, PFe-II and PFe-III) were prepared by adjusting the feeding amount of SPIONs, in which the practical SPIONs loading amounts was 1.83%, 1.38% and 1.16%, respectively. The average diameter of the fabricated microspheres ranged from 160 μm to 200 μm, having the porous and rough surfaces displayed by SEM. Moreover, they displayed the magnetic property with a saturation magnetization of 0.16 emu/g. In vitro cell studies showed that most of BMSCs were adhered on the surface of PFe-II microspheres after 2 days of co-culture. Moreover, the osteoblasts differentiation of BMSCs was significantly promoted by PFe-II microspheres after 2 weeks of co-culture, as shown by detecting osteogenesis-related proteins expressions of ALP, COL I, OPN and OCN. Afterward, PFe-II microspheres were surgically implanted into the defect zone of rat femoral bone, followed by exposure to an external MF, to evaluate their bone repairing effect in vivo . At 6th week after treatment with PFe-II + MF, the bone mineral density (BMD, 263.97 ± 25.99 mg/cm 3 ), trabecular thickness (TB.TH, 0.58 ± 0.08 mm), and bone tissue volume/total tissue volume (BV/TV, 78.28 ± 5.01%) at the defect zone were markedly higher than that of the PFe-II microspheres alone (BMD, 194.34 ± 26.71 mg/cm 3 ; TB.TH, 0.41 ± 0.07 mm; BV/TV, 50.49 ± 6.41%). Moreover, the higher expressions of ALP, COL I, OPN and OCN in PFe-II + MF group were displayed in the repairing bone. Collectively, magnetic PLGA microspheres together with MF may be a promising strategy for repairing bone defects.
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