Cell Stem Cell
·
2024
·
IF 19.8
Haiyue Dang,Panpan Feng,Shuning Zhang,Lihua Peng,Shuli Xing,Yuchen Li,Xiang Wen,Liqiang Zhou,Shyamal Goswami,Mingbing Xiao,Nick Barker,Philippe Sansonetti,Parag Kundu
The maternal microbiome influences child health. However, its impact on a given offspring’s stem cells, which regulate development, remains poorly understood. To investigate the role of the maternal microbiome in conditioning the offspring’s stem cells, we manipulated maternal microbiota using Akkermansia muciniphila . Different maternal microbiomes had distinct effects on proliferation and differentiation of neuronal and intestinal stem cells in the offspring, influencing their developmental trajectory, physiology, and long-term health. Transplantation of altered maternal microbiota into germ-free mice transmitted these stem cell phenotypes to the recipients’ offspring. The progeny of germ-free mice selectively colonized with Akkermansia did not display these stem cell traits, emphasizing the importance of microbiome diversity. Metabolically more active maternal microbiomes enriched the levels of circulating short-chain fatty acids (SCFAs) and amino acids, leaving distinct transcriptomic imprints on the mTOR pathway of offsprings’ stem cells. Blocking mTOR signaling during pregnancy eliminated the maternal-microbiome-mediated effects on stem cells. These results suggest a fundamental role of the maternal microbiome in programming offsprings’ stem cells and represent a promising target for interventions.
研究领域:
微生物学
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干细胞生物学
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发育生物学
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生理学
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健康科学
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DOI
PubMed
高影响因子
Bioactive Materials
·
2024
·
IF 18
Jian Wang,Dongyang Zhou,Ruiyang Li,Shihao Sheng,Guangfeng Li,Yue Sun,Peng Wang,Yulin Mo,Han Liu,Xiao Chen,Zhen Geng,Qin Zhang,Yingying Jing,Long Bai,Ke Xu,Jiacan Su
Bone organoids are emerging as powerful tools for studying bone development and related diseases. However, the simplified design of current methods somewhat limits their application potential, as these methods produce single-tissue organoids that fail to replicate the bone microarchitecture or achieve effective mineralization. To address this issue, we propose a three-dimensional (3D) construction strategy for generating mineralized bone structures using bone marrow-derived mesenchymal stem cells (BMSCs). By mixing BMSCs with hydrogel to create a bone matrix-mimicking bioink and employing projection-based light-curing 3D printing technology, we constructed 3D-printed structures, which were then implanted subcutaneously into nude mice, away from the native bone microenvironment. Even without external stimulation, these implants spontaneously formed mineralized bone domains. With long-term culture, these structures gradually matured into fully differentiated bone tissue, completing both mineralization and vascularization. This in vivo bone organoid model offers a novel platform for studying bone development, exploring congenital diseases, testing drugs, and developing therapeutic applications.
研究领域:
组织工程
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再生医学
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干细胞生物学
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骨骼发育
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药物测试
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DOI
PubMed
高影响因子
BIOGERONTOLOGY
·
2026
·Vol. 27
·期 5
·174
·
IF 5.3
Chen Meijuan,Zhang Min,Mei Hanyi,Bai Xinyu,Wang Xiaoli,Tang Yijun,Jiang Hua,Zhang Lulu,Zhou Chunfang,Yuan Yahong
Hematopoiesis depends on the sustained function of hematopoietic stem and progenitor cells (HSPCs). However, aging progressively impairs HSPC function, contributing to immunosenescence, hematologic malignancies, and degenerative disorders. Therefore, elucidating the mechanisms underlying HSPC aging is essential for developing strategies to alleviate age-related dysfunction. Here, we identify angiopoietin-like 8 (ANGPTL8), a secreted glycoprotein known for its role in glucose and lipid metabolism, as a novel regulator of HSPC aging. Systemic ANGPTL8 knockout significantly attenuated senescence-associated phenotypes in multiple murine tissues. In vitro and in vivo analyses of proliferation, colony-forming capacity, mitochondrial membrane potential, senescence-associated secretory phenotype (SASP) expression, reactive oxygen species (ROS) accumulation, myeloid skewing, and early hematopoietic regeneration further demonstrated that ANGPTL8 promotes HSPC aging. Mechanistically, ANGPTL8 deficiency activated the PI3K/AKT signaling pathway, whereas a PI3K activator rescued the senescence effects induced by recombinant ANGPTL8 (rANGPTL8). Furthermore, co-immunoprecipitation (Co-IP) confirmed that rANGPTL8 directly interacts with the transmembrane receptor PirB. Recombinant PirB (rPirB) reduced the phosphorylation of PI3K/AKT, whereas PirB knockdown effectively blocked the inhibitory effect of rANGPTL8 on PI3K/AKT phosphorylation. Collectively, our findings suggest that ANGPTL8 drives HSPC aging primarily by suppressing the PI3K/AKT pathway via its receptor PirB, providing a new potential target to alleviate the aging of HSPCs.
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高影响因子
Science Advances
·
2026
·Vol. 12
·期 19
·
IF 13.9
Wentao Zhang,Yiqi Shen,Shuangxu Jia,Yingxin Chen,Ruisi Cai,Yunlong Jiao,Quanquan Han,Jiahuan You,Shiqi Wang,Xingyi Wan,Jicheng Yu,Zhen Gu,Zhuxiao Gu,Yuqi Zhang
Ischemic heart disease and related sequelae pose tremendous burdens on worldwide medical care. The excessive activation of cardiomyocytes and cardiac fibroblasts further exacerbates the prognosis after necrosis. Decades of stem cell therapy in preclinical studies suggested promising results in cardiomyocyte regeneration and tissue remodeling. However, few formulations achieved clinical translation due to the limited stem cell engraftment and insufficient arousal of resident cardiomyocytes. Here, we reported an implantable electroactive device to leverage stem cell therapy and cardiomyocyte restoration for effective heart recovery. Assisted by the piezoelectric microneedle patch with 80–cubic millimeter cavity, 1.5 × 10 5 mesenchymal stem cells could be delivered efficiently to the infarcted site and sustained longer for continuous paracrine effects. Meanwhile, the piezoelectric stimulation generated from the poly( l -lactic) acid microneedle matrix further potentiated the stem cells and elicited more vigorous self-repair responses in cardiomyocytes. This approach was validated to effectively suppress inflammatory monocytes, reduce cardiomyocyte necrosis, and improve heart remodeling in a rat heart infarction model.
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
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2019
·
IF 4.511
Jianghong Huang,Yujie Liang,Zhiwang Huang,Pengchao Zhao,Qian Liang,Yonglong Liu,Li Duan,Wei Liu,Feiyan Zhu,Liming Bian,Jiang Xia,Jianyi Xiong,Daping Wang
Pulsed electromagnetic field therapy, or pulsed signal therapy, has shown efficacy in treating many illnesses, including knee osteoarthritis. Although the mechanism is not fully understood, magnetic therapy is broadly welcomed because of its safe and noninvasive nature. At the cellular and molecular level, remote control of the cell fate by the magnetic field also has profound applications in both basic science and translational research. Here we demonstrate the use of pulsed electromagnetic field, one of the most benign and noninvasive extracellular cues, as a novel method to control specific chondrogenic differentiation of mesenchymal stem cells (MSCs). Chondrogenesis of transplanted MSCs inside the joint is considered one of the future therapies to rebuild the damaged cartilage. Here we show that pulsed electromagnetic field promotes chondrogenic differentiation of MSCs, and such a promoting effect can be drastically enhanced by the combined use of a magnetic hydrogel as the cell growth matrix. The magnetic hydrogel, synthesized by chemical cross-linking of gelatin and β-cyclodextrin and by embedding Fe3O4 magnetic nanoparticles in the hydrogel network, supports adhesion, growth, and proliferation of MSCs. Pulsed electromagnetic field boosts chondrogenesis of MSCs grown on the magnetic hydrogel, manifested by enhanced toluidine blue staining; higher expression of collagen II protein; and upregulation of collagen II, aggrecan, and SOX9 genes. Therefore, our work presents a robust method for chondrogenesis of MSCs using magnetic field as the external cue.
研究领域:
细胞生物学
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再生医学
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生物材料学
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DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2019
·Vol. 177
·期 3
·687-700
·
IF 6.583
Huihong Zeng,Huan Li,Mengzhen Yue,Ying Fan,Jiaoqi Cheng,Xincheng Wu,Rui Xu,Wuping Yang,Manjun Li,Jiahui Tang,Hongping Chen,Bohai Kuang,Guangqin Fan,Qingxian Zhu,Lijian Shao
Background and Purpose Damage to intestinal epithelial cells and mucosa limits the effectiveness of several anti-cancer chemotherapeutic agents but the underlying mechanism (s) remain unknown. Little is known of how enteric nervous system regulates proliferation, differentiation, impairment, and regeneration of intestinal stem cells. Here we have investigated the effects of isoprenaline on the damaged intestinal stem cells induced by chemotherapeutic treatments in mice. Experimental Approach The effects of inhibiting sympathetic and parasympathetic nerves on intestinal stem cells were examined in male C57BL/6J mice. Protection by isoprenaline of intestinal stem cells was assessed in the presence or absence of 5-fluorouracil (5FU) or cisplatin. Cellular apoptosis, cell cycle, PI3K/Akt signalling, and NF-κB signalling in intestinal stem cells were mechanistically evaluated. Key Results The sympathetic nerve inhibitor 6-OHDA decreased the number and function of intestinal stem cells. 5FU or cisplatin treatment damaged both intestinal stem cells and sympathetic nerves. Notably, isoprenaline accelerated the recovery of intestinal stem cells after 5FU or cisplatin treatment. This protective effect of isoprenaline on damaged intestinal stem cells was mediated by β 2 -adrenoceptors. The benefits of isoprenaline were mainly mediated by inhibiting cellular apoptosis induced by 5FU treatment, which might contribute to fine-tuning regulating NF-κB signalling pathway by isoprenaline administration. Conclusions and Implications Treatment with isoprenaline is a new approach to ameliorate the damage to intestinal stem cells following exposure to cancer chemotherapeutic agents.
研究领域:
药理学
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肿瘤学
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胃肠病学
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神经科学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2017
·
IF 2.759
Biao Zhou,Xiaolong Lu,Zhi Tang,Dan Liu,Youliang Zhou,Peng Zeng,Hui Xiong
With the advent of aging, the morbidity rates of such diseases as osteoarthritis , rheumatoid arthritis , and osteoporosis has witnessed a significant increase. As a common rattan drug , sinomenine (SIN) has been widely applied for the treatment of various arthritic diseases in traditional Chinese medicine (TCM) clinics. Given that SIN has been reported to inhibit the expression of Prostaglandin E2 (PGE2) in several types of cells, in this study, the influence of SIN treatment on PGE2 expression in mesenchymal stem cells (MSCs), thereby changing the osteoprotegerin (OPG) receptor/activator for the nuclear factor-κ B ligand (RANKL) ratio, was investigated. Our results showed that, when compared with the untreated cells, treatment with 0.25 mM SIN can down-regulate the mRNA and protein expression levels of the Prostaglandin E synthase 3 (PTGES3) or PGE2 and RANKL , while the OPG was up-regulated. After being cultured with SIN treated MSC-conditioned medium (stMSC-CM), the amount of TRAP-positive multinucleated osteoclasts differentiated from RAW264.7 cells was reduced. Also, the expression levels of specific markers for active osteoclasts were decreased when incubated with stMSC-CM. Moreover, these changes were able to be recovered when the exogenous RANKL was added to the MSC-CM culture . This indicates that the increased OPG/RANKL ratio can reduce the osteoclastogenesis of RAW264.7 cells. Our results demonstrated that SIN has an inhibitory effect on osteoclast differentiation through mechanisms involving the inhibition of the PGE2-induced OPG/RANKL ratio. SIN can also serve as a proinflammatory mediator to regulate the MSC immunosuppressive effects. Our findings suggest that SIN can be useful for the treatment of bone diseases associated with over-activity of osteoclasts.
研究领域:
药理学
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免疫学
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细胞生物学
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干细胞研究
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骨病治疗
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2023
·Vol. 35
·期 52
·2307169
·
IF 29.4
Huihui He,Yuan Yuan,Yunhong Wu,Jingyi Lu,Xiaofu Yang,Kejie Lu,An Liu,Zelin Cao,Miao Sun,Mengfei Yu,Huiming Wang
The integration of abiotic materials with live cells has emerged as an exciting strategy for the control of cellular functions. Exoskeletons consisting ofmetal–organic frameworks are generated to produce partial-coated bone marrow stem cells (BMSCs) to overcome low cell survival leading to disappointing effects for cell-based cardiac therapy. Partially coated exoskeletons can promote the survival of suspended BMSCs by integrating the support of exoskeletons and unimpaired cellular properties. In addition, partial exoskeletons exhibit protective effects against detrimental environmental conditions, including reactive oxygen species, pH changes, and osmotic pressure. The partial-coated cells exhibit increased intercellular adhesion forces to aggregate and adhere, promoting cell survival and preventing cell escape during cell therapy. The exoskeletons interact with cell surface receptors integrin α5β1, leading to augmented biological functions with profitable gene expression alteration, such as Vegfa, Cxcl12, and Adm. The partial-coated BMSCs display enhanced cell retention in infarcted myocardium through non-invasive intravenous injections. The repair of myocardial infarction has been achieved with improved cardiac function, myocardial angiogenesis, proliferation, and inhibition of cell apoptosis. This discovery advances the elucidation of potential molecular and cellular mechanisms for cell-exoskeleton interactions and benefits the rational design and manufacture of next-generation nanobiohybrids.
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PubMed
高影响因子
Drug Design Development and Therapy
·
2024
·
IF 4.7
Yu Li,Guangren Yue,Shuying Yu,Zheng Liu,Yilin Cao,Ximei Wang
Introduction Autologous stem cell transplantation has emerged as a promising strategy for bone repair. However, the osteogenic potential of mesenchymal stem cells derived from diabetic patients is compromised, possibly due to hyperglycemia-induced senescence. The objective of this study was to assess the preconditioning effects of extracellular vesicles derived from H2O2-stimulated adipose-derived stem cells (ADSCs) and non-modified ADSCs on the osteogenic potential of diabetic bone marrow mesenchymal stem cells (BMSCs).Methods Sprague-Dawley (SD) rats were experimentally induced into a diabetic state through a high-fat diet followed by an injection of streptozotocin, and diabetic BMSCs were collected from the bone marrow of these rats. Extracellular vesicles (EVs) were isolated from the conditioned media of ADSCs, with or without hydrogen peroxide (H2O2) preconditioning, using density gradient centrifugation. The effects of H2O2 preconditioning on the morphology, marker expression, and particle size of the EVs were analyzed. Furthermore, the impact of EV-pretreatment on the viability, survivability, migration ability, osteogenesis, cellular senescence, and oxidative stress of diabetic BMSCs was examined. Moreover, the expression of the Nrf2/HO-1 pathway was also assessed to explore the underlying mechanism. Additionally, we transplanted EV-pretreated BMSCs into calvarial defects in diabetic rats to assess their in vivo bone formation and anti-senescence capabilities.Results Our study demonstrated that pretreatment with EVs from ADSCs significantly improved the viability, senescence, and osteogenic differentiation potential of diabetic BMSCs. Moreover, in-vitro experiments revealed that diabetic BMSCs treated with H2O2-activated EVs exhibited increased viability, reduced senescence, and enhanced osteogenic differentiation compared to those treated with non-modified EVs. Furthermore, when transplanted into rat bone defects, diabetic BMSCs treated with H2O2-activated EVs showed improved bone regeneration potential and enhanced anti-senescence function t compared to those treated with non-modified EVs. Both H2O2-activated EVs and non-modified EVs upregulated the expression of the Nrf2/HO-1 pathway in diabetic BMSCs, however, the promoting effect of H2O2-activated EVs was more pronounced than that of non-modified EVs.Conclusion Extracellular vesicles derived from H2O2-preconditioned ADSCs mitigated senescence in diabetic BMSCs and enhanced their bone regenerative functions via the activation of the Nrf2/HO-1 pathway.
研究领域:
干细胞生物学
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再生医学
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细胞衰老
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骨再生
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氧化应激
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产品关联
DOI
PubMed
高影响因子
BIOPOLYMERS
·
2018
·Vol. 109
·期 7
·e23223
·
IF 1.99
Yue Yang,Zuyuan Luo,Ying Zhao
The scaffolds for stem cell-based bone tissue engineering should hold the ability to guide stem cells osteo-differentiating. Otherwise, stem cells will differentiate into unwanted cell types or will form tumors in vivo. Alginate, a natural polysaccharide with great biocompatibility, was widely used in biomedical applications. However, the limited bioactivity and poor osteogenesis capability of pristine alginate hampered its further application in tissue engineering. In this work, a bone forming peptide-1 (BFP-1), derived from bone morphogenetic protein-7, was grafted to alginate polymer chains to prepare peptide-decorated alginate porous scaffolds (pep-APS) for promoting osteo-differentiation of human mesenchymal stem cells (hMSCs). SEM images of pep-APS exhibited porous structure with about 90% porosity (pore size 100–300 μm), which was appropriate for hMSCs ingrowth. The adhesion, proliferation and aggregation of hMSCs grown on pep-APS were enhanced in vitro. Moreover, pep-APS promoted the alkaline phosphatase (ALP) activity of hMSCs, and the osteo-related genes expression was obviously up-regulated. The immunochemical staining and western blot analysis results showed high expression level of OCN and Col1a1 in the hMSCs grown on pep-APS. This work provided a facile and valid strategy to endow the alginate polymers themselves with specific bioactivity and prepare osteopromoting scaffold with enhanced osteogenesis ability, possessing potential applications in stem cell therapy and regenerative medicine. Graphical
研究领域:
组织工程
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干细胞生物学
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材料科学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Journal of Environmental Chemical Engineering
·
2023
·
IF 7.7
Yuan Chen,Yuancai Chen,Yexia Qin
In the present study, we found that nanoparticles (Pd-NPs) were biosynthesized by Bacillus wiedmannii MSM ( B. wiedmannii MSM) with endogenous carbon under O 2 condition, and more favorablity under N 2 purging condition. XRD results indicated that crystal planes of Pd-NPs were attributed to Pd 0 (111), Pd 0 (200), Pd 0 (220), and Pd 0 (311), respectively. TEM and STEM-EDX results showed that the bio-reduction of Pd (II) ( k pd,1 =4.799 min −1 ) occurred predominately in periplasm space. FTIR results showed that the -COOH, -OH, and -NH 2 were the main groups participating in the removal of Pd (II). The aerobic reduction of Pd (II) by B. wiedmannii MSM was proposed, including extracellular superoxide radicals produced by NAD(P)H oxidases , endogenous electron donors, and O 2 -insensitive hydrogenase. These studies provide new methods and insights for reduction of Pd (II).
研究领域:
环境科学
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材料科学
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微生物学
·
化学
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DOI
高影响因子
APPLIED CLAY SCIENCE
·
2020
·
IF 4.605
Yixuan Yang,Runliang Zhu,Qingze Chen,Haoyang Fu,Qiuzhi He,Jianxi Zhu,Hongping He
Multifunctional adsorbents based on montmorillonite (Mt) have been of highly concerns due to their unique 2D layer structures and impressive co-adsorption performances. To further enhance the support ability and reactivity, a strategy was developed in this study to enable the co-existence of porous nanosilica (PNS) and hydrophobic interlayer spaces in Mt structure, and a novel multifunctional adsorbent (iron modified-acidified organo-Mt, Fe-AOMt) was then synthesized, aiming to simultaneously remove hydrophobic contaminants , oxyanion contaminants and heavy metals in water. The combination of XRD , FTIR and TEM verified the co-existence of amorphous PNS and layered structure (containing intercalated surfactant) in the acidified organo-Mt (AOMt), and results of STEM-EDX revealed uniform distribution of Fe after the further introduction of Fe hydroxides to AOMt. Additionally, pore structure analyses suggested that the acid activation can obviously increase the pore volume and specific surface area of OMt. Batch adsorption experiments revealed that Fe-AOMt as a promising multifunctional adsorbent was able to effectively and simultaneously remove nitrobenzene , phosphate, and Cd(II) in the multi-contaminant system. The synergetic adsorption of phosphate and Cd(II) on Fe-AOMt suggested the formation of ternary surface complexes (≡Fe–P–Cd), while the pH-independent uptake of nitrobenzene was hardly influenced by adsorption of phosphate and Cd(II), implying dissimilar adsorption mechanisms. The co-adsorption mechanism on Fe-AOMt was further revealed via XPS . Our work provided a novel and efficient Mt-based multifunctional adsorbent with a newly-proposed structure, which was a preliminary exploration of diversifying locations and types of active sites in Mt structure.
研究领域:
环境科学
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材料科学
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化学工程
·
水处理
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DOI
高影响因子
危险品化学品经营许可证（带存储）