BIOMACROMOLECULES
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2025
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IF 5.4
Simiao Yu,Chenyu Liu,Zhangrong Lou,Weihong Qiao
The application of stem cell therapy for neural tissue regeneration is often limited by low cell survival after transplantation. To overcome this, we developed an injectable hydrogel via dual cross-linking: Schiff base formation between oxidized alginate and silk fibroin (SF) and host–guest interactions between β-cyclodextrin (β-CD) and adamantane. The resulting hydrogel exhibits high water content, injectability, electrical conductivity, suitable degradation, and excellent biocompatibility. Neural stem cells (NSCs) encapsulated within the hydrogel showed high viability, proliferation, and neuronal differentiation capacity in vitro. In a rat model of cerebral palsy (CP), NSC-laden hydrogel transplanted via intracranial injection promoted significant structural repair and functional recovery, as confirmed by behavioral tests, histology, and proteomics. indicating its potential therapeutic effect on the repair of cerebral tissue in CP. This indicates that the hydrogel has broad application prospects in the field of brain nerve tissue repair.
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PubMed
高影响因子
Frontiers in Chemistry
·
2024
·
IF 3.8
Sun Jingxuan,He Lina,An Qi,Ye Xu,Ma Jinjie,Yan Jing,Xie Xiaoqi,Sun Xiangyu,Niu Yumei,Cao Wenxin
Introduction: Facial nerve injury significantly impacts both the physical and psychological] wellbeing of patients. Despite advancements, there are still limitations associated with autografts transplantation. Consequently, there is an urgent need for effective artificial grafts to address these limitations and repair injuries. Recent years have witnessed the recognition of the beneficial effects of chitosan (CS) and graphene in the realm of nerve repair. Dental pulp stem cells (DPSCs) hold great promise due to their high proliferative and multi-directional differentiation capabilities.Methods: In this study, Graphene/CS (G/CST) composite tubes were synthesized and their physical, chemical and biological properties were evaluated, then DPSCs were employed as seed cells and G/CST as a scaffold to investigate their combined effect on promoting facial nerve injury repair.Results and Disscussion: The experimental results indicate that G/CST possesses favorable physical and chemical properties, along with good cyto-compatibility. making it suitable for repairing facial nerve transection injuries. Furthermore, the synergistic application of G/CST and DPSCs significantly enhanced the repair process for a 10 mm facial nerve defect in rabbits, highlighting the efficacy of graphene as a reinforcement material and DPSCs as a functional material in facial nerve injury repair. This approach offers an effective treatment strategy and introduces a novel concept for clinically managing facial nerve injuries.
研究领域:
生物医学工程
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组织工程
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干细胞研究
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神经科学
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高影响因子
iScience
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2024
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IF 4.6
WenYe Liu,Xi Liu,LingYa Li,ZhiPeng Tai,GuoLiang Li,Jing-Xia Liu
Summary Enhancers of polycomb 1 (EPC1) and 2 (EPC2) are involved in multiple biological processes as components of histone acetyltransferases/deacetylase complexes and transcriptional cofactors, and their dysfunction was associated with developmental defects and diseases. However, it remains unknown how their dysfunction induces hematopoietic stem and progenitor cell (HSPC) defects. Here, we show that depletion of EPC1 / 2 significantly reduced the number of hematopoietic stem and progenitor cells (HSPCs) in the aorta-gonad mesonephros and caudal hematopoietic tissue regions by impairing HSPC proliferation, and consistently downregulated the expression of HSPC genes in K562 cells. This study demonstrates the functions of EPC1 / 2 in regulating histone H3 acetylation, and in regulating DLST (dihydrolipoamide S-succinyltransferase) via H3 acetylation and cooperating with transcription factors serum response factor and FOXR2 together, and in the subsequent HSPC emergence and proliferation. Our results demonstrate the essential roles of EPC1 / 2 in regulating H3 acetylation, and DLST as a linkage between EPC1 and EPC2 with mitochondria metabolism, in HSPC emergence and proliferation.
研究领域:
血液学
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分子生物学
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细胞生物学
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表观遗传学
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高影响因子
MOLECULAR PHARMACEUTICS
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2013
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IF 4.57
Yongping Shi,Zhigui Su,Sai Li,Yinan Chen,Xi Chen,Yanyu Xiao,Minjie Sun,Qineng Ping,Li Zong
Refractory leukemia remains the most common therapeutic problem in clinical treatment of leukemia. The key therapy of refractory leukemia is to kill, thoroughly, the minimal residual disease and leukemia stem cells in the highly vascularized red marrow areas. In this study, two new conjugates, alendronate-polyethylene glycol (100) monostearate and folate-polyethylene glycol (100) monostearate, were synthesized to develop a multistep targeting nanostructured lipid carriers by enhancing drug transport to the high bone turnover areas adjacent to the red marrow and targeting the minimal residual disease and leukemia stem cells. This dual targeting system demonstrated a great binding affinity to hydroxyapatite, a model component of bone minerals, and higher cell uptake (in the form of carriers but not drug) and cytotoxicity in the K562 cell line, a leukemia cell line with overexpressed folate receptors, were observed in vitro compared to unmodified carriers, especially when the cells were pretreated and the receptors were up-regulated by all-trans retinoic acid. The comodel test of K562 cells and HA showed that this dual targeting system could desorb from bone surface and be taken up by leukemia cells. For the in vivo study, this dual targeting system exhibited a significant increase in plasma half-life and could specifically accumulate in the bone tissue of rats or mice after intravenous injection. Ex vivo imaging of mice femurs and confocal laser scanning microscope imaging of mice femur slices further confirmed that this dual targeting system could favorably deposit to the osteoblast-enriched areas of high bone turnover in regions of trabecular bone surrounded by red marrow. In vivo antitumor activity in K562/BALB/c-nu leukemia mice showed that the treatment of this dual targeting system significantly reduced the white blood cell (WBC) number in peripheral blood and bone marrow to the normal level. In conclusion, this dual targeting system could precisely target to the regions where the minimal residual disease and leukemia stem cells are located and then be specifically uptaken in large amounts, which is a valuable target for refractory leukemia therapy.
研究领域:
药学
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肿瘤学
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生物医学工程
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DOI
高影响因子
Frontiers in Cell and Developmental Biology
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2024
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IF 4.6
Zhao Liusha,Luo Ting,Zhang Hong,Fan Xinxin,Zhang Qiaoqiao,Chen Haiyang
Introduction: Intestinal stem cells (ISCs) are crucial for tissue repair and homeostasis because of their ability to self-renew and differentiate. However, their functionality declines significantly with age, resulting in reduced tissue regeneration and a higher risk of age-related diseases. Addressing this decline in ISC performance during aging presents a substantial challenge. The specific impact of nutrients or dietary elements on ISC adaptive resizing is urgent to explore.Methods: Drosophila ISCs are an ideal model for studying development and aging because of their genetic richness, ease of manipulation, and similarity to mammalian tissues. As the primary mitotically active cells in the Drosophila gut, ISCs are flexible in response to dietary and stress signals. Manipulating signaling pathways or dietary restrictions has shown promise in regulating ISC functions and extending lifespan in flies, these approaches face broader applications for aging research.Results: Kaempferol is well-regarded for its antioxidant, anti-inflammatory, and potential anticancer effects. However, its impacts on ISCs and the associated mechanisms remain inadequately understood. Our findings indicate that Kaempferol accelerates gut recovery after damage and improves the organism’s stress tolerance. Moreover, Kaempferol suppresses the hyperproliferation of aging ISCs in Drosophila. Further investigation revealed that the regulatory effects of Kaempferol on ISCs are mediated through the reduction of endoplasmic reticulum (ER) stress in aging flies and the modulation of excessive reactive oxygen species (ROS) levels via ER-stress pathways. Furthermore, Kaempferol exerts regulatory effects on the insulin signaling pathway, thereby contributing to the attenuation of ISC senescence.Discussion: This study reveals that Kaempferol promotes intestinal homeostasis and longevity in aging flies by targeting ER stress and insulin signaling pathways, though the exact molecular mechanisms require further exploration. Future research will aim to dissect the downstream signaling events involved in these pathways to better understand how Kaempferol exerts its protective effects at the molecular level.
研究领域:
细胞生物学
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营养学
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衰老研究
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DOI
高影响因子
DEVELOPMENTAL CELL
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2023
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IF 11.8
Xue-Lian Sun,Zhen-Hua Chen,Xize Guo,Jingjing Wang,Mengmeng Ge,Samuel Zheng Hao Wong,Ting Wang,Si Li,Mingze Yao,Laura A. Johnston,Qing-Feng Wu
Cell competition acts as a quality-control mechanism that eliminates cells less fit than their neighbors to optimize organ development. Whether and how competitive interactions occur between neural progenitor cells (NPCs) in the developing brain remains unknown. Here, we show that endogenous cell competition occurs and intrinsically correlates with the Axin2 expression level during normal brain development. Induction of genetic mosaicism predisposes Axin2-deficient NPCs to behave as "losers" in mice and undergo apoptotic elimination, but homogeneous ablation of Axin2 does not promote cell death. Mechanistically, Axin2 suppresses the p53 signaling pathway at the post-transcriptional level to maintain cell fitness, and Axin2-deficient cell elimination requires p53-dependent signaling. Furthermore, mosaic Trp53 deletion confers a "winner" status to p53-deficient cells that outcompete their neighbors. Conditional loss of both Axin2 and Trp53 increases cortical area and thickness, suggesting that the Axin2-p53 axis may coordinate to survey cell fitness, regulate natural cell competition, and optimize brain size during neurodevelopment.
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高影响因子
ACS Nano
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2023
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IF 17.1
Mengjiao Ma,Faxing Zou,Bahatibieke Abudureheman,Feng Han,Guoli Xu,YaJie Xie,Kun Qiao,Jiang Peng,Yueping Guan,Haoye Meng,Yudong Zheng
Magnetic biomaterials are widely used in the field of tissue engineering because of their functions such as drug delivery and targeted therapy. In this study, a magnetically responsive composite microcarrier was prepared through in situ polymerization of dopamine with Fe3O4 (MS) to form a complex. The magnetic composite microcarriers are paramagnetic and have certain magnetic responsiveness, suitable pore size porosity for cell growth, and good blood compatibility and biocompatibility. The bone marrow mesenchyml stem cells (BMSCs) were cultured on magnetic composite microcarriers, and a static magnetic field (SMF) was applied. The results showed that BMSCs adhered to the microcarriers proliferated under the action of horizontal and vertical forces. Magnetic composite microcarriers loaded with BMSCs were implanted into the SD rat model of cartilage defect, and a magnet was added to the operative side. After 12 weeks, cartilage regeneration was observed. The results of gross observation and histological immunostaining 1 month, 2 months, and 3 mounths after operation showed that the magnetic composite microcarriers of loaded cells promoted the early maturation of cartilage and collagen secretion, and the effect of cartilage repair was significantly better than that of the control group. Gait analysis showed that implanting magnetic composite microcarriers loaded with stem cells can reduce postoperative pain and promote limb recovery in SD rats. In conclusion, this study suggests that magnetic composite microcarriers are promising tissue-engineered scaffolds for cartilage regeneration and repair.
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Advanced Healthcare Materials
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2023
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IF 10
Yangyang Qu,Si He,Shixing Luo,Jinmin Zhao,Ruiming Liang,Chuanan Liao,Li Zheng
Due to the limited therapeutic efficacy of current treatments, articular cartilage regeneration is still challenging work. Scaffold-based tissue engineering provides a promising strategy for cartilage regeneration, but most scaffolds are limited by poor mechanical properties or unfavorable biocompatibility. Here, a novel photocrosslinkable, injectable locust bean gum (LBG)–methacrylate (MA) hydrogel is reported as a biomimetic extracellular matrix (ECM) for cartilage repair with minimal invasive operation. LBG-MA hydrogels show controllable degradation rate and improve mechanical properties and excellent biocompatibility. More importantly, LBG-MA hydrogel significantly induces bone mesenchymal stem cells to chondrogenic differentiation in vitro, as evidenced by high accumulation of cartilage-specific ECM components glycosaminoglycan and upregulated expression of key chondrogenic genes ( collagen type II , aggrecan , and sex determining region Y-box9 ). Besides, the hydrogel is injectable, which can be in situ crosslinked via UV irradiation. Further, the photocrosslinkable hydrogels accelerate cartilage healing in vivo after 8 weeks of therapy. A strategy is provided here for photocrosslinkable, injectable, biodegradable scaffold fabrication based on native polysaccharide polymer for minimal invasive cartilage repair.
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JOURNAL OF NANOBIOTECHNOLOGY
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2023
·Vol. 21
·期 1
·1-19
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IF 10.2
Lu Lu,Quan Lingli,Li Jian,Yuan Junbin,Nie Xinmin,Huang Xueyuan,Dong Hang,Su Yanrong,Huang Yufen,Kou Qingjie,Liu Leping,Liu Haiting,Zhou Xionghui,Gui Rong,Gu Lan
Background Sepsis is a syndrome of physiological, pathological and biochemical abnormalities caused by infection. Although the mortality rate is lower than before, many survivors have persistent infection, which means sepsis calls for new treatment. After infection, inflammatory mediators were largely released into the blood, leading to multiple organ dysfunction. Therefore, anti-infection and anti-inflammation are critical issues in sepsis management.Results Here, we successfully constructed a novel nanometer drug loading system for sepsis management, FZ/MER-AgMOF@Bm. The nanoparticles were modified with LPS-treated bone marrow mesenchymal stem cell (BMSC) membrane, and silver metal organic framework (AgMOF) was used as the nanocore for loading FPS-ZM1 and meropenem which was delivery to the infectious microenvironments (IMEs) to exert dual anti-inflammatory and antibacterial effects. FZ/MER-AgMOF@Bm effectively alleviated excessive inflammatory response and eliminated bacteria. FZ/MER-AgMOF@Bm also played an anti-inflammatory role by promoting the polarization of macrophages to M2. When sepsis induced by cecal ligation and puncture (CLP) challenged mice was treated, FZ/MER-AgMOF@Bm could not only reduce the levels of pro-inflammatory factors and lung injury, but also help to improve hypothermia caused by septic shock and prolong survival time.Conclusion sTogether, the nanoparticles played a role in combined anti-inflammatory and antimicrobial properties, alleviating cytokine storm and protecting vital organ functions, could be a potential new strategy for sepsis management.
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ACS Nano
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2023
·
IF 17.1
Guanghao Wu,Zhenya Liu,Changwen Mu,Da Song,Jiaxin Wang,Xiangxi Meng,Ziyuan Li,Hong Qing,Yuping Dong,Hai-Yan Xie,Dai-Wen Pang
The intrinsic features and functions of platelets and mesenchymal stem cells (MSCs) indicate their great potential in the treatment of intracerebral hemorrhage (ICH). However, neither of them can completely overcome ICH because of the stealth process and the complex pathology of ICH. Here, we fabricate hybrid cells for versatile and highly efficient ICH therapy by fusing MSCs with platelets and loading with lysophosphatidic acid-modified PbS quantum dots (LPA-QDs). The obtained LPA-QDs@FCs (FCs = fusion cells) not only inherit the capabilities of both platelets and MSCs but also exhibit clearly enhanced proliferation activated by LPA. After systemic administration, many proliferating LPA-QDs@FCs rapidly accumulate in ICH areas for responding to the vascular damage and inflammation and then efficiently prevent both the primary and secondary injuries of ICH but with no obvious side effects. Moreover, the treatment process can be tracked by near-infrared II fluorescence imaging with highly spatiotemporal resolution, providing a promising solution for ICH therapy.
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Antioxidants
·
2022
·Vol. 12
·期 1
·59
·
IF 7.675
La Yan,Xiaoxin Guo,Juanyu Zhou,Yuedan Zhu,Zehong Zhang,Haiyang Chen
Adult stem cells, a class of cells that possess self-renewal and differentiation capabilities, modulate tissue regeneration, repair, and homeostasis maintenance. These cells undergo functional degeneration during aging, resulting in decreased tissue regeneration ability and increased disease incidence. Thus, it is essential to provide effective therapeutic solutions to preventing the aging-related functional decline of stem cells. Quercetin (Que) is a popular natural polyphenolic flavonoid found in various plant species. It exhibits many beneficial effects against aging and aging-related diseases; however, its efficacy against adult stem cell aging remains largely unclear.Drosophilapossesses a mammalian-like intestinal system with a well-studied intestinal stem cell (ISC) lineage, making it an attractive model for adult stem cell research. Here, we show that Que supplementation could effectively prevent the hyperproliferation of ISCs, maintain intestinal homeostasis, and prolong the lifespan in agedDrosophila. In addition, we found that Que could accelerate recovery of the damaged gut and improve the tolerance ofDrosophilato stressful stimuli. Furthermore, results demonstrated that Que prevents the age-associated functional decline of ISCs via scavenging reactive oxygen species (ROS) and inhibiting the insulin signaling pathway. Overall, our findings suggest that Que plays a significant role in delaying adult stem cell aging.Keywords:intestinal stem cell;aging;quercetin;insulin signaling;ROS;Drosophila
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Journal of Stomatology Oral and Maxillofacial Surgery
·
2022
·
IF 2.48
Yi Sun,Jianlu Shi,Xiaoan Luo,Xuehong Xu
Objective Human periodontal ligament stem cells (hPDLSCs) refer to one kind of somatic stem cells that are capable of differentiating into multiple cell kinds and undergoing robust clonal self-renewal. This work was unearthed to elucidate the possible molecular mechanism of miR-142–3p in mediating osteogenic differentiation of hPDLSCs by targeting SGK1 . Methods The hPDLSCs were isolated, cultured, and identified. hPDLSCs were identified by immunofluorescence staining and multiple differentiation ability detection. Cell proliferation ability was assessed by CCK-8 assay. hPDLSCs were induced using osteogenic differentiation medium. ALP activity was detected by alkaline phosphatase (ALP) staining and ALP activity assay, and mineralized nodule formation was determined by alizarin red staining. The expression levels of osteogenic differentiation marker proteins ALP, RUNX2, and OCN were measured by RT-qPCR. miR-142–3p candidate targets were obtained through bioinformatics analysis. The relationship between miR-142–3p and SKG1 was verified. Results miR-142–3p in hPDLSCs after osteogenic induction was down-regulated. Elevated miR-142–3p restricted hPDLSCs proliferation, and diminished ALP activity and mineralized nodule formation, as well as the expression of ALP, RUNX2, and OCN, while miR-142–3p inhibition led to inverse results. miR-142-3p inhibited SKG1 expression. SKG1 overexpression promoted hPDLSC proliferation and osteogenic differentiation, and reversed the inhibitory function of miR-142–3p on hPDLSCs. Conclusion This study highlights that miR-142–3p represses osteogenic differentiation of hPDLSCs by reducing SGK1 expression.
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