Journal of Materials Chemistry B
·
2020
·Vol. 9
·期 2
·440-452
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IF 5.344
Minghao Yao,Jinrui Li,Junni Zhang,Shanshan Ma,Luyu Wang,Feng Gao,Fangxia Guan
Recently, an advanced stem cell and tissue engineering approach has been recognized as an emerging and fascinating strategy to promote neural repair in spinal cord injury (SCI). Hydrogels can be properly engineered to encapsulate cells, enhance cell viability and neural differentiation, and provide the advantage of flexible adaptation to irregular defects. In this study, a dual-enzymatically cross-linked gelatin hydrogel with hydrogen horseradish peroxidase (HRP) and galactose oxidase (GalOx) was proposed to combine human umbilical cord mesenchymal stem cells (hUC-MSCs) for facilitating nerve regeneration post-SCI. In vitro, hUC-MSCs in this 3D gelatin hydrogel displayed good viability, proliferation, and neuronal differentiation. To further evaluate the neural regeneration effect of hUC-MSCs loaded into gelatin hydrogels in vivo, a clinically-relevant and force-controlled contusion model of mouse spinal cords was established. We found that implantation of a hydrogel loaded with hUC-MSCs significantly promoted the motor function recovery evaluated by Basso Mouse Scale (BMS) and footprint tests. Further histological analysis showed that the hydrogel and hUC-MSC combined transplantation dramatically decreased inflammation, inhibited apoptosis and promoted neurogenesis. Overall, implantation of this dual-enzymatically cross-linked and MSC-laden 3D gelatin hydrogel is a promising therapeutic strategy for SCI treatment.
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Small
·
2020
·Vol. 16
·期 16
·1906915
·
IF 11.459
Chengyan Wang,Jiani Xie,Xinghua Dong,Linqiang Mei,Maoru Zhao,Zhengwei Leng,Houxiang Hu,Lele Li,Zhanjun Gu,Yuliang Zhao
The exploration of an old drug for new biomedical applications has an absolute predominance in shortening the clinical conversion time of drugs for clinical application. In this work, carbon nanoparticles suspension injection (CNSI), the first clinically approved carbon nanoparticles in China, is explored as a new nano-radioprotective agent for potent intestinal radioprotection. CNSI shows powerful radioprotective performance in the intestine under oral administration, including efficient free radical scavenging ability, good biosafety, high chemical stability, and relatively long retention time. For example, CNSI shows high reactive oxygen species (ROS) scavenging activities, which effectively alleviates the mitochondrial dysfunction and DNA double-strand breaks to protect the cells against radiation-induced damage. Most importantly, this efficient ROS scavenging ability greatly helps restrain the apoptosis of the small intestinal epithelial and crypt stem cells, which decreases the damage of the mechanical barrier and thus relieves radiation enteritis. Moreover, CNSI helps remove the free radicals in the intestinal microenvironment and thus maintain the balance of intestinal flora so as to mitigate the radiation enteritis. The finding suggests a new application of clinically approved carbon nanoparticles, which not only promotes the development of new intestinal radioprotector, but also has a great potential for clinical transformation.
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Frontiers in Bioengineering and Biotechnology
·
2021
·
IF 5.89
Dong Wenpei,Song Zhicheng,Liu Suihong,Yu Ping,Shen Zhipeng,Yang Jianjun,Yang Dongchao,Hu Qinxi,Zhang Haiguang,Gu Yan
Application of synthetic or biological meshes is the main therapy for the repair and reconstruction of abdominal wall defects, a common disease in surgery. Currently, no ideal materials are available, and there is an urgent need to find appropriate ones to satisfy clinical needs. Electrospun scaffolds have drawn attention in soft tissue reconstruction. In this study, we developed a novel method to fabricate a composite electrospun scaffold using a thermoresponsive hydrogel, poly (N-isopropylacrylamide)-block-poly (ethylene glycol), and a biodegradable polymer, polylactic acid (PLA). This scaffold provided not only a high surface area/volume ratio and a three-dimensional fibrous matrix but also high biocompatibility and sufficient mechanical strength, and could simulate the native extracellular matrix and accelerate cell adhesion and proliferation. Furthermore, rat adipose-derived stem cells (ADSCs) were seeded in the composite electrospun scaffold to enhance the defect repair and regeneration by directionally inducing ADSCs into endothelial cells. In addition, we found early vascularization in the process was regulated by the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway. In our study, overexpression of HIF-1α/VEGF in ADSCs using a lentivirus system promoted early vascularization in the electrospun scaffolds. Overall, we expect our composite biomimetic scaffold method will be applicable and useful in abdominal wall defect regeneration and repair in the future.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Jiayi He,Zuqing Hu,Zhenjie Gao,Renyi Liu,Zhujun Kang,Shuyi Lan,Yang Wang,Shanshan He,Hongyi Xian,Fatoumata Diallo,Yunxia Jiang,Jiguo Wu,Suli Huang,Ziquan Lv,Dalin Hu
Lead is an important heavy metal material and also an omnipresent environmental pollutant, which poses extensive hazards to human health, including its nephrotoxicity. However, there are still many unknowns regarding its toxic mechanism and intervention strategy. Here, we revealed that lead exposure promoted the activation of PERK in HK - 2 cells (p - PERK and the ratio of p - PERK / PERK increased), enhanced the expression of its molecular chaperone binding immunoglobulin protein (BIP) and its downstream signaling molecule CCAAT / enhancer - binding protein homologous protein (CHOP). This indicated that lead exposure resulted in the occurrence of the unfolded protein response (UPR) in HK - 2 cells. Further, lead induced significant DNA damage, oxidative stress and apoptosis in HK-2 cells. Especially, when human umbilical cord mesenchymal stem cell - derived exosomes (hucMSC - exos) were ingested by HK-2 cells, all the levels of p - PERK, p - PERK / PERK ratio, BIP and CHOP were significantly down - regulated, which suggested that the UPR was significantly alleviated. Simultaneously, the above-mentioned toxic effects of lead were significantly reduced. Moreover, when GSK2606414 was employed to block the phosphorylation of PERK, the toxic effects of lead were also significantly alleviated. Hence, we conclude that hucMSC - exos can alleviate the toxicity of lead to HK-2 cells via interfering with the UPR, in which PERK plays a crucial role, and it may be a promising target for intervening in the toxicity of lead.
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TISSUE & CELL
·
2022
·
IF 2.586
Hongjian Tan,Yiwen Wang,Zehua Zou,Yufei Xing,Zuowei Shi,Kaifu Wang,Daming Dong
Objective The critical role of circular RNAs (circRNAs) in osteoporosis (OP) has been highlighted. We tried to explore the role of circPVT1 in OP in relation to microRNA-30d-5p (miR-30d-5p) and ITGB3. Methods After bone marrow collection, bone marrow mesenchymal stem cells (BMSCs) were isolated and identified. Then, Pearson coefficient was used to analyze the correlation among circPVT1, miR-30d-5p and ITGB3, and the binding sites were predicted and verified. Gain- and loss-of function assays in circPVT1, miR-30d-5p and ITGB3 were performed to analyze their effect on osteogenic differentiation of BMSCs. Results The osteogenic differentiation of BMSCs from OP patients was significantly decreased, and reduced circPVT1 expression was found in the BMSCs from OP patients. Overexpression of circPVT1 stimulated the formation of calcified nodules, increased alkaline phosphatase activity, and enhanced the expression of osteogenic marker genes in the BMSCs from OP patients. Additionally, circPVT1 expression was negatively correlated with miR-30d-5p, and miR-30d-5p was negatively correlated with ITGB3 in OP patients. Mechanically, circPVT1 regulated the osteogenic differentiation potential of BMSCs by relieving the inhibition of miR-30d-5p on ITGB3 through the competitive endogenous RNA mechanism. Conclusion Our study highlighted a circPVT1/miR-30d-5p/ITGB3 axis in regulating osteogenic differentiation potential of BMSCs from OP patients.
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Nanomedicine
·
2026
·
IF 4.6
Jing Zhang,Dongdong Gao
Background Hepatocellular carcinoma (HCC) remains a highly aggressive malignancy with poor therapeutic outcomes due to drug resistance, systemic toxicity, and limited tumor-targeted drug delivery. This study aimed to develop dual-drug-loaded exosome nanocarrier encapsulating rapamycin (RAP) and Astragaloside IV (AST-IV) (RAP@AST-IV/EXO NC) to inhibit PI3K/Akt/mTOR signaling and enhance mitochondrial apoptosis in HCC.Methods Bone marrow mesenchymal stem cell-derived exosomes (BM-MSC-Exos) were isolated and used for co-delivery of RAP and AST-IV via sonication-assisted loading. Physicochemical properties, drug loading, and release behavior were evaluated. In vitro efficacy was assessed through cell viability, apoptosis, ROS generation, mitochondrial membrane potential, migration, and Western blot assays. In vivo therapeutic efficacy and safety were evaluated in male BALB/c mice bearing HepG2 xenografts.Results RAP@AST-IV/EXO NC showed favorable physicochemical characteristics, sustained drug release, enhanced apoptosis, increased ROS generation, mitochondrial membrane disruption, and inhibition of cancer cell migration. The RAP@AST-IV/EXO NC significantly reduced cell viability and suppressed phosphorylated PI3K, Akt, and mTOR expression while activating mitochondrial apoptotic markers. In vivo, RAP@AST-IV/EXO NC markedly inhibited tumor growth without evident systemic toxicity.Conclusion RAP@AST-IV/EXO NC represent a promising biocompatible strategy for targeted HCC therapy through combined PI3K/Akt/mTOR inhibition and mitochondrial apoptosis induction.
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POLYMER TESTING
·
2026
·
IF 6.4
Yuchu Yang,Xiong Xiao,Ziwei Huang,Hongying Duan,Liping Yang,Li Feng
GOx/HRP crosslinked HAA-Tyr hydrogel system which with robust temperature-independent anti-swelling and self-contracting capability was developed. • Accompany with excellent self-contracting property, HAA-Tyr hydrogel showed excellent cytocompatibility that enables stem cell encapsulation and delivery. • Through integrating mechanical-biological clues of HAA-Tyr and ADSCs, ADSC@HAA-Tyr wound dressing showed enhanced performance in guiding full-thickness skin regeneration. Wound dressing combining mechanical cues and the biological activity of stem cells is a promising candidate for chronic wound healing. Here, we developed an adipose-derived mesenchymal stem cells (ADSCs) loaded self-contractile and tissue-adhesive hydrogel patch cross-linked via the peroxidase (HRP) and glucose oxidase (GOx) mediated cascade enzymatic crosslinking of aldehyde tyramine-dual modified hyaluronic acid (HAA-Tyr). Apart from the great cell encapsulation ability, aldehyde modified hyaluronic acid (HAA) hydrogel exhibited excellent self-contraction and tissue adhesion properties, which are beneficial for wound closure. Moreover, the ADSCs-loaden HAA-Tyr hydrogel showed improved bioactivity in promoting cell migration and neovascularization. The in vivo full-thickness skin defect model showed that the hydrogel dressing significantly promoted the wound healing process through enhancing angiogenesis and reducing early inflammatory response. In conclusion, wound dressings developed by integrating autonomously contractile, tissue-adhesive hydrogel systems with stem cell paracrine functionality hold considerable promise for chronic wound management.
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JOURNAL OF ETHNOPHARMACOLOGY
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2026
·
IF 6.8
Teng Wang,Weilin Liu,Chunyi Lyu,Yunxiao Luo,Xinyu Tang,Chen Han,Ruirong Xu
Ethnopharmacological relevance Realgar is an arsenic-containing mineral medicine and a key component of Realgar-Indigo naturalis formula, an oral traditional Chinese medicine preparation clinically used in China for acute promyelocytic leukemia (APL), a biologically distinct subtype of acute myeloid leukemia (AML). Realgar Transforming Solution (RTS) is a microbially processed realgar preparation. Its activity in AML stem cell-like contexts outside APL remains insufficiently defined, particularly in cell-line-derived CD34 + CD38 − LSC-like models. Aim of the study: To evaluate whether RTS suppresses stemness-associated phenotypic features in KG-1a-derived CD34 + CD38 − LSC-like cells and to explore its association with endoplasmic reticulum stress (ERS), mitochondrial injury, and mitophagy-related alterations. Materials and methods CD34 + CD38 − LSC-like cells were enriched from KG-1a cells and used as a cell-line-derived in vitro model. Cell viability, apoptosis, cell cycle, CD34 + CD38 − fraction, colony formation, and TIM3/ HAVCR2 expression were assessed after RTS treatment. RNA sequencing, Ca 2+ measurement, ROS detection, mitochondrial membrane potential assay, MDC staining, western blotting, RT-qPCR, immunofluorescence, and transmission electron microscopy were performed. 4-phenylbutyric acid and Mdivi-1 were used as pharmacological rescue agents. Results RTS reduced the CD34 + CD38 − fraction, colony formation, and TIM3/ HAVCR2 expression, while inducing apoptosis in KG-1a-derived LSC-like cells. Transcriptomics implicated ER protein processing, unfolded protein response, apoptosis, autophagy, and mitophagy-related pathways. RTS increased Ca 2+ levels, ROS accumulation, mitochondrial depolarization, PERK-eIF2α-ATF4-CHOP signaling, and PINK1/Parkin-associated mitophagy-like marker changes. 4-phenylbutyric acid and Mdivi-1 partially rescued RTS-impaired LSC-like phenotypic features, supporting pathway involvement. Conclusions RTS suppressed stemness-associated phenotypic features in a KG-1a-derived CD34 + CD38 − LSC-like model. These effects were associated with ERS, mitochondrial injury, and PINK1/Parkin-related mitophagy-like alterations.
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Stem Cell Research & Therapy
·
2025
·Vol. 16
·期 1
·1-22
·
IF 7.3
Ding Kang,Wang Xinyu,Liu Wei,Chen Yating,Xue Fangrui,Song Chunru,Dong Yishan,Zhai Jun,Liang Chengguang,Li Jing
Background Polycystic Ovary Syndrome (PCOS), is a complex endocrine disorder affecting 6–21% of reproductive-aged women, characterized by chronic anovulation, hyperandrogenism, and polycystic ovarian morphology. Current clinical management relies on lifestyle modifications and symptom-targeted therapies due to the absence of curative interventions. In recent years, Laparoscopic ovarian drilling (LOD), a surgical procedure that induces controlled ovarian damage to stimulate primordial follicle activation and regulate follicular growth, has emerged as an established therapeutic intervention for infertility in PCOS. Beyond surgical approaches, the 740Y-P peptide—PI3K-Akt pathway agonist can achieve similar effects to LOD in enhancing follicular activation and restoring fertility. However, translating 740Y-P into clinical practice remains challenging due to systemic delivery limitations, including poor bioavailability and inadequate ovarian targeting. To address this, naturally secreted sEVs have gained attention as versatile therapeutic vectors owing to their intrinsic immunomodulatory properties and homing tendency. Methods In this study, We engineered HucMSC-sEVs through anchor peptide-mediated surface Connections to deliver the 740Y-P peptide. The N-terminus of 740Y-P was conjugated to the C-terminus of the CD63-binding anchor peptide, enabling exogenous loading via co-incubation (4 °C, 12h). Engineered sEVs were characterized for peptide loading efficiency and targeting capability. PCOS model mice were treated by tail vein injection. The phenotype studies were explored by glucose homeostasis, insulin sensitivity, ovarian weight, ovarian morphometric analysis, follicle counts and litter size. The mechanisms were also investigated by immunohistochemistry, immunofluorescence, western blot, RT-qPCR and TUNEL assays. And compared the different efficacy of 740Y-P peptide, sEVs, and 740Y-P loaded sEVs. Results Our results demonstrated that sEVs functioned as dual-effect agents—serving both as immunomodulators and targeted delivery vehicles for 740Y-P, significantly improved ovarian microenvironment and enhanced ovarian targeting efficiency of 740Y-P. The engineered sEVs restored estrous cycles, ameliorated glucose-insulin homeostasis, reduced ovarian inflammation and granulosa cell apoptosis. Additionally, activated the PI3K/Akt signaling pathway to promote follicular maturation, reduce ovarian cyst formation and ultimately increase litter size, improving metabolic and reproductive outcomes in PCOS mice. Conclusions In this study, we engineered sEVs to deliver the 740Y-P peptide, demonstrating their capacity to mitigate ovarian inflammation, normalize follicular development, and enhance fertility in a PCOS mouse model. These findings propose a novel therapeutic strategy for PCOS, pending further optimization of delivery protocols and clinical validation. Graphical Engineered modified MSCs sEVs loaded with 740Y P peptide showed
synergistic therapeutic effects through a dual mechanism of action: (1) restoration of t he ovarian
microenvironment by exploiting the intrinsic immunomodulatory and anti apoptotic properties of
sEVs, (2) enhancement of PI3K/Akt signaling in the ovary by increasing the specific targeting of
740Y P.
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FITOTERAPIA
·
2026
·
IF 2.9
Wei Xiao,Shuting Zhai,Kuangyi Liu,Zhijian Lu,Xizi Yongbo,Yi Liu,Ruiyin Ye,Mingzhen He,Zhiqiang Li
This study aimed to elucidate the sedative–hypnotic effects of a stem–derived bioactive fraction from Syringa oblata Lindl. (ZDX) and to reveal its underlying mechanisms, thereby providing a theoretical and practical basis for the development of new sleep aid drugs. ZDX was prepared by optimizing the extraction and purification procedures. Using UPLC–Q–TOF–MS, the prototype compounds absorbed into the brain of insomnia mice were analyzed, and 15 bioactive compounds were identified or predicted, including Dihydrocubebin, (−)-Cubebin, Isoguamarol, and others. Its efficacy and mechanisms were investigated using network pharmacology, transcriptomics, metabolomics, and molecular docking, complemented by in vivo pharmacodynamic and molecular analyses. In an insomnia mouse model, ZDX significantly increased body weight, reduced sleep latency, and prolonged total sleep duration, while alleviating anxiety and depression–like behaviors and improving histopathological damage in the hippocampus and hypothalamus, showing significant sedative–hypnotic effects. Mechanistically, ZDX modulated key genes and proteins involved in the cAMP signaling pathway, enhanced superoxide dismutase activity, reduced malondialdehyde levels, decreased inflammatory cytokines (IL–6, IL–1β, and TNF–α), and restored neurotransmitter homeostasis in the brain. Collectively, ZDX exerts sedative–hypnotic effects, at least in part, by activating the cAMP/PKA–CREB–BDNF axis and coordinately regulating neurotransmission, oxidative stress, and inflammation.
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2023
·
IF 4.9
Yuying Bai,Dawei Tian,Zhengxin Ren,Dangyang Yue,Qian Ren,Li Pei,Jun Pan
Though magnetic iron oxide nanoparticles (IONPs) are approved for clinical use as contrast agents for MR imaging in United States and Europe, and are widely used to label cells in research, the relationship between IONPs and mesenchymal stem cells (MSCs) is not fully addressed. Here the effects of consistently appeared γ-Fe 2 O 3 on the lineage commitment of MSCs were studied to optimize applications of IONPs in MSCs upon verification of viability. 30 nm 10 μg/mL induced highest promotions on osteogenesis, while 30 and 50 nm of 100 μg/mL elicited most chondrogensis in 14 days, where the effects on ALP, GAG and SOX9 appeared after 7 days, while on RUNX2 came out after 10 days. γ-Fe 2 O 3 enhanced intracellular and extracellular Fe 3+ and ROS, modulated F-actin and decreased Lamin A of MSCs at different time scale. The disturbances of F-actin, Lamin A or ROS altered the effects of γ-Fe 2 O 3 on MSC differentiation. Our results demonstrate that different size, concentration and modulation of γ-Fe 2 O 3 are needed in its MSC applications for bone and cartilage tissues. Furthermore, an undocumented phenomenon that the modulation of F-actin affected the Lamin A expression in MSCs was observed.
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Small
·
2022
·Vol. 18
·期 23
·2201123
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IF 15.153
Jing Li,Yao Zhang,Zhichao Lou,Mingxi Li,Lin Cui,Zhenrong Yang,Lijuan Zhang,Yu Zhang,Ning Gu,Fang Yang
Neural stem cells (NSCs) are used to treat various nervous system diseases because of their self-renewal ability and multidirectional differentiation potential. However, an insufficient ability to track their migration in vivo and poor control over their survival and differentiation efficiency are two major critical challenges for clinical application. Here, it is shown that when magnetic nanobubbles (MNBs), which are assembled from magnetic nanoparticles, are internalized by NSCs, intramembrane volumetric oscillation of the MNBs induces an increase in intracellular hydrostatic pressure and cytoskeleton force, resulting in the activation of the Piezo1-Ca 2+ mechanosensory channel. This subsequently triggers the BMP2/Smad biochemical signaling pathway, leading to differentiation of NSCs into the neuronal phenotype. Signaling through the Piezo1-Ca 2+ -BMP2/Smad pathway can be further accelerated by application of an external shear stress force using low-intensity pulsed ultrasound. More importantly, magnetic resonance imaging and ultrasound imaging surveillance of NSCs based on MNB labeling can be leveraged to provide NSC therapeutic outcomes. Both the in vitro and in vivo findings demonstrate that a bubble nanostructure-induced physical force can modulate and control the mechanical signaling pathway regulating stem cell development.
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