Materials Today Communications
·
2025
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IF 4.5
Liuxin Yang,Guanhua Jiao,Dandan Wei,Tianzhu Zhang
Microspheres have shown great potential as biomaterial substrates for culturing and expanding stem cells to meet the requirements of cell therapy. Gelatin microspheres have been widely researched in cell culture; however, the size, pore structure, and stability of these microspheres still need to be further optimized. In this study, gelatin methacrylamide (GelMA) and glycidyl-methacrylate-modified silk fibroin (SFMA) composite microspheres (denoted as GSM microspheres) were synthesized using a simple water-oil (W/O) emulsion method followed by photo-crosslinking. The swelling ratio (34 % (w/v) GelMA = 799.8 ± 67.7 %; 34 % (w/v) GSM = 643.1 ± 66.3 %) and degradation ratio (relative weights at 15 d: 34 % (w/v); GelMA = 13.3 ± 3.9 %; 34 % (w/v) GSM = 38.6 ± 6.2 %) of GSM microspheres decreased with the incorporation of SFMA. Moreover, the constructed microspheres demonstrated adjustable size distribution (from 75 to 775 µm for GM0 to 25–275 µm for GSM3), pore structure, and surface curvature. Thus, the initial cell adhesion efficiency of microspheres increased with the content of GelMA (GSM1, GSM2, and GSM3 was 39.5 %, 23.3 %, and 7.7 %, respectively), and the cell amplification achieved by microsphere-microsphere transfer demonstrates the potential for cell expansion in vitro . In addition, On the higher curvature surface of GSM3, the cells were overspread and the shape factor of the nucleus was high (0.88 ± 0.05). Alkaline phosphatase (ALP) activity, osteogenesis-related gene expression, and Alizarin Red S staining showed that the addition of SFMA could promote osteogenic differentiation of BMSCs. Thus, the composite microspheres can serve as an adjustable three-dimensional (3D) culture platform for the amplification and osteogenic differentiation of BMSCs.
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Advanced Science
·
2024
·
IF 14.3
Kai Yuan,Yiqi Yang,Yixuan Lin,Feng Zhou,Kai Huang,Shengbing Yang,Weiqing Kong,Fupeng Li,Tianyou Kan,Yao Wang,Caiqi Cheng,Yakun Liang,Haishuang Chang,Jie Huang,Haiyong Ao,Zhifeng Yu,Hanjun Li,Yihao Liu,Tingting Tang
The specific mechanisms underlying bacteria-triggered cell death and osteogenic dysfunction in host bone marrow mesenchymal stem cells (BMSCs) remain unclear, posing a significant challenge to the repair of infected bone defects. This study identifies ferroptosis as the predominant cause of BMSCs death in the infected bone microenvironment. Mechanistically, the bacteria-induced activation of the innate immune response in BMSCs leads to upregulation and phosphorylation of interferon regulatory factor 7 (IRF7), thus facilitating IRF7-dependent ferroptosis of BMSCs through the transcriptional upregulation of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4). Moreover, it is found that intervening in ferroptosis can partially rescue cell injuries and osteogenic dysfunction. Based on these findings, a hydrogel composite 3D-printed scaffold is designed with reactive oxygen species (ROS)-responsive release of antibacterial quaternized chitosan and sustained delivery of the ferroptosis inhibitor Ferrostatin-1 (Fer-1), capable of eradicating pathogens and promoting bone regeneration in a rat model of infected bone defects. Together, this study suggests that ferroptosis of BMSCs is a promising therapeutic target for infected bone defect repair.
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Food Bioscience
·
2025
·
IF 5.9
Ruirui Li,Dongyue Yang,Zhiyu Li,Xiaohong Tang,Ke Zhong,Yan Ding,Xiaomei Han,Xueqiang Guan,Yuxia Sun
Grapes grown in the Yantai wine region typically exhibit lower phenolic content and sugar levels, resulting in wines with relatively lower sensory quality. This study aims to assess the impact of stem-contact fermentation on the quality of wines from this region. Cabernet Sauvignon and Merlot grapes were selected winemaking, using three approaches: 100% destemming, and stem-contact fermentation with 10% and 20% grape stems, respectively. After alcoholic fermentation, the wines were analyzed for oenological parameters, phenolic compounds, color parameters, volatile compounds, and sensory evaluation. The results showed that stems did not negatively impact the oenological parameters. In Cabernet Sauvignon wines, stems resulted in a significant increase in total phenolics, anthocyanins, and tannins. In Merlot wines, stems caused a significant increase in total phenolics and a notable reduction in total anthocyanins. Stems primarily affected the anthocyanin content in both Cabernet Sauvignon and Merlot wines, with minimal effects on the proportions of individual anthocyanins. PLS-DA analysis further revealed that stems significantly affected the levels of total tannins, (−)-epigallocatechin, and total phenolic compounds in Cabernet Sauvignon wines, as well as the levels of (−)-epigallocatechin and total phenolics in Merlot wines. The presence of grape stems also significantly influenced the volatile compounds in the wine. When 20% of grapes retained their stems, there was a trend toward higher volatile content, resulting a more complex aroma profile. Overall, retaining some stems during fermentation is an effective strategy to enhance the quality of wines from the Yantai wine region.
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Cell Reports Medicine
·
2025
·
IF 10.6
Wenjing Wang,Guihong Lu,Peilin Guo,Haochong Zhang,Yan Wang,Diwei Zheng,Chengliang Lyu,Dongfang Wang,Shang Li,Feng Li,Jiawei Zhao,Meng Qin,Weiping Li,Hui Tan,Guanghui Ma,Wei Wei
Oxidative damage and neuroinflammation are the key features of central nervous system (CNS) injury. Inspired by the neuroprotective properties of neural stem cell-derived exosomes (NExo) and the reactive oxygen species (ROS) scavenging ability of selenium, we develop an advanced NExo bearing ultrasmall nano-selenium (∼3.5 nm) via lipid-mediated nucleation (SeNExo). In addition to maintaining the biological components of NExo, the resulting SeNExo exhibits a Se–O bond that dramatically enhances its ROS-scavenging performance. SeNExo penetrates the blood-brain barrier (BBB) via the apolipoprotein E and prolow-density lipoprotein receptor-related protein 1 (APOE_LRP-1) interaction. Through proteomics, microRNA (miRNA) omics, and single-nucleus RNA sequencing, we find that SeNExo can alleviate neuronal apoptosis, restore glia homeostasis, and remodel glia-neuron networks. Therefore, SeNExo confers potent therapeutic benefits, significantly reducing cerebral lesions in a murine traumatic brain injury model. Even extending to a murine spinal cord injury model, SeNExo promotes locomotory recovery, further supporting SeNExo as a neotype and a promising therapeutic agent for treating traumatic CNS injury.
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ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Jianmei Chen,Chun Pan,Ya Gao,Qihong Chen,Xueying An,Zongguang Liu
Cell-based therapies offer tremendous potential for skin flap regeneration. However, the hostile microenvironment of the injured tissue adversely affects the longevity and paracrine effects of the implanted cells, severely reducing their therapeutic effectiveness. Here, an injectable hydrogel (nGk) with reactive oxygen species (ROS) scavenging capability, which can amplify the cell viability and functions of encapsulated mesenchymal stem cells (MSCs), is employed to promote skin flap repair. nGk is formulated by dispersing manganese dioxide nanoparticles (MnO2 NPs) in a gelatin/κ-carrageenan hydrogel, which exhibits satisfactory injectable properties and undergoes a sol–gel phase transition at around 40 °C, leading to the formation of a solid gel at physiological temperature. MnO2 NPs enhance the mechanical properties of the hydrogel and give it the ability to scavenge ROS, thus providing a cell-protective system for MSCs. Cell culture studies show that nGk can mitigate the oxidative stress, improve cell viability, and boost stem cell paracrine function to promote angiogenesis. Furthermore, MSC-loaded nGk (nGk@MSCs) can improve the survival of skin flaps by promoting angiogenesis, reducing inflammatory reactions, and attenuating necrosis, providing an effective approach for tissue regeneration. Collectively, injectable nGk has substantial potential to enhance the therapeutic benefits of MSCs, making it a valuable delivery system for cell-based therapies.
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ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Wenhui Ge,Yijun Gao,Yiyu Zeng,Yi Yu,Xiaoyan Xie,Liangle Liu
Oral ulcers, superficial lesions on the surface of the oral mucosa, have a high incidence rate, and their main symptoms include local pain and erosion. Lipopolysaccharide (LPS)-preconditioned bone marrow mesenchymal stem cells and their secreted exosomes (LPS-pre-Exos) have been shown to promote recovery in various inflammatory conditions and wounds. However, studies documenting LPS-pre-Exos as a therapeutic intervention for oral mucosal-like diseases are lacking. In this study, we prepared a silk fibroin microneedle (MN) patch consisting of LPS-pre-Exos and zeolitic imidazolate framework-8 (ZIF-8) that localized at the tip and base, respectively, and used this MN patch for oral ulcer treatment. Upon insertion into the oral mucosa, continuous LPS-pre-Exos release was observed, which promoted macrophage polarization and tissue healing. Additionally, the ZIF-8 framework in the MN patch facilitated the controlled release of Zn2+, which demonstrated potent antimicrobial properties via synergistic effects. The in vitro experimental results showed that the silk fibroin MN patch can continuously release LPS-pre-Exos and Zn2+ for more than 7 days. Thus, the LPS-pre-Exos and ZIF-8-loaded silk fibroin MN patch exhibited good anti-inflammatory and antibacterial properties, promoting oral ulcer healing, and showed good histocompatibility. Hence, it may represent a potentially valuable strategy for facilitating oral ulcer healing.
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BIOMATERIALS
·
2025
·
IF 12.9
Zixuan Dong,Song Liu,Xiaobing Liu,Dong He,Qi Chu,Linjie Zhong,Xiangyu Yu,Xiaoling Fu
Diabetes is closely associated with the onset and prognosis of myocardial infarction (MI). However, current treatment strategies primarily focus on addressing MI, often neglecting the detrimental effects of hyperglycemia, a hallmark of diabetes. Hyperglycemia disrupts the crucial transition of macrophages from the M1 to M2 phenotype, thereby exacerbating MI-induced tissue damage and impeding myocardial repair. Mitochondria have emerged as key regulators of macrophage phenotype, suggesting the potential for modulating macrophages through mitochondria transfer. In this study, we developed microvesicles containing active mitochondria (Mito@euMVs), derived from enucleated mesenchymal stem cells. We found that 86.3% of the Mito@euMVs contained mitochondria, with no nuclear material present. Mito@euMVs effectively delivered mitochondria into macrophages, facilitating their transit from M1 to M2 phenotype, even in hyperglycemia. Further in vivo study using a diabetic rat model of MI confirmed their cardiac repair properties. Treatment of Mito@euMVs led to 24.55±4.33% improvement in ejection fraction and 15.48±4.04% in fractional shortening 28 days post-MI in diabetic rats. Additionally, Mito@euMVs mitigated infarcted left ventricular wall thinning and fibrosis, enhanced M2 macrophage phenotype, promoted cardiomyocyte survival. Our study emphasizes the effective modulation of macrophage phenotype via mitochondrial transfer with Mito@euMVs and highlights their promising potential in treating MI.
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Photodiagnosis and Photodynamic Therapy
·
2024
·
IF 3.1
Haotian Li,Wenwen Yang,Biao Zhu,Miao Li,Xinran Zhang
Background Photobiomodulatiom therapy (PBMT) has biostimulatory effects on bone marrow mesenchymal stem cells (BMSCs), which takes a pivotal role in maintaining bone mass and avoiding osteoporosis (OP). Autophagy is an important regulator for cell survival and homeostasis. Previous researchers found that BMSCs derived from osteoporotic rats (OP-BMSCs) were with the feature of reduced osteogenic differentiation and autophagy dysfunction. However, the potential regulation of PBMT in osteogenic differentiation of OP-BMSCs and its underling relationship with autophagy remain unclear. Methods 650 nm red light-emitting diode (LED) was selected to initiate PBMT effects. The isolation and culture of OP-BMSCs were implemented after the establishment of the OP rat model. Firstly, the optimal dose of LED was screened on OP-BMSCs by CCK-8. Meanwhile, the osteogenic and mineralization activities were studied through the detection of Alkaline phosphatase (ALP) and alizarin red S (ARS). Then, the levels of osteogenesis and autophagy were investigated via western blot and immunofluorescence staining. Finally, the autophagy inhibitor 3-MA was applied to illustrate the underlying mechanism of the osteogenic effect of PBMT on OP-BMSCs. Results Firstly, the optimal dose of 6 J/cm 2 LED was selected in the subsequent experiments according to CCK-8. Then, the ALP activity and the mineralization ability of OP-BMSCs were obviously increased by PBMT. Meanwhile, Runx-2, OCN and OPN were significantly upregulated in LED group. Furthermore, the expressions of autophagic proteins increased significantly in LED group by immunofluorescence staining and western blot assay. At last, the promoted effects of PBMT on osteogenic differentiation in OP-BMSCs were distinctly reversed via inhibiting autophagy. Conclusion Our research illustrated that 650 nm LED could improve osteogenic differentiation of OP-BMSCs, suggesting a potential correlation between PBMT-mediated activation of autophagy and promotion of osteogenic differentiation.
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MOLECULAR THERAPY
·
2025
·
IF 12
Qian Yu,Ke Jiang,Siyu Ma,Quan Zheng,Serena Tondi,Chiara Reina,Berina Šabanović,Chenlei Wen,Baiyong Shen,Alexandra Aicher,Haiyun Song,Yinxing Ma,Christopher Heeschen
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor prognosis, partly due to cancer stem cells (CSCs) that drive progression and treatment resistance. We explored the therapeutic potential of inducing cuproptosis, a copper-dependent regulated cell death, in CSC-enriched PDAC models. Using human and murine PDAC models, we evaluated elesclomol, a copper transport enhancer. Elesclomol alone had minimal effects; combined with copper chloride (CuCl 2 ), it significantly and irreversibly reduced CSC phenotypes without affecting non-transformed cells. Mechanistically, only the combination raised intracellular copper ions 2–4-fold, decreased iron–sulfur cluster proteins, and caused fatty acylated DLAT accumulation in mitochondria, triggering cuproptosis, particularly in CSCs. It also selectively inhibited copper-dependent antioxidant SOD1 in PDAC cells, impairing oxidative stress defense and sensitizing them to copper-induced death. To enhance clinical relevance, CuCl 2 was replaced with hollow mesoporous copper sulfide nanoparticles releasing copper ions. Either combined with or loaded with elesclomol, these nanoparticles similarly increased copper levels and inhibited PDAC spheroid formation. In vivo , in aggressive immunocompetent murine PDAC models, this nanoparticle-based treatment significantly improved gemcitabine response. These findings identify nanoparticle-mediated cuproptosis induction, combined with standard chemotherapy, as an innovative CSC-targeting strategy to improve PDAC outcomes, offering new hope for PDAC patients.
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Bioactive Materials
·
2023
·
IF 18.9
Hongyan Wei,Fenfang Li,Tiantian Xue,Haixia Wang,Enguo Ju,Mingqiang Li,Yu Tao
As the most abundant liver-specific microRNA, microRNA-122 (miR122) played a crucial role in the differentiation of stem cells into hepatocytes. However, highly efficient miR122 delivery still confronts challenges including poor cellular uptake and easy biodegradation. Herein, we for the first time demonstrated that the tetrahedral DNA (TDN) nanoplatform had great potential in inducing the differentiation of human mesenchymal stem cells (hMSCs) into functional hepatocyte-like cells (HLCs) by transferring the liver-specific miR122 to hMSCs efficiently without any extrinsic factors. As compared with miR122, miR122-functionalized TDN (TDN-miR122) could significantly up-regulate the protein expression levels of mature hepatocyte markers and hepatocyte-specific marker genes in hMSCs, indicating that TDN-miR122 could particularly activate the hepatocyte-specific properties of hMSCs for developing cell-based therapies in vitro . The transcriptomic analysis further indicated the potential mechanism that TDN-miR122 assisted hMSCs differentiated into functional HLCs. The TDN-miR122-hMSCs exhibited hepatic cell morphology phenotype, significantly up-regulated specific hepatocyte genes and hepatic biofunctions in comparison with the undifferentiated MSCs. Preclinical in vivo transplantation appeared that TDN-miR122-hMSCs in combination with or without TDN could efficiently rescue acute liver failure injury through hepatocyte function supplement, anti-apoptosis, cellular proliferation promotion, and anti-inflammatory. Collectively, our findings may provide a new and facile approach for hepatic differentiation of hMSCs for acute liver failure therapy. Further large animal model explorations are needed to study their potential in clinical translation in the future.
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ACS Applied Materials & Interfaces
·
2015
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IF 6.723
Mengke Wang,Yi Deng,Ping Zhou,Zuyuan Luo,Qiuhong Li,Bingwu Xie,Xiaohong Zhang,Tong Chen,Duanqing Pei,Zhihui Tang,Shicheng Wei
Human pluripotent stem cells (hPSCs) are a promising cell source with pluripotency and capacity to differentiate into all human somatic cell types. Designing simple and safe biomaterials with an innate ability to induce osteoblastic lineage from hPSCs is desirable to realize their clinical adoption in bone regenerative medicine. To address the issue, here we developed a fully defined synthetic peptides-decorated two-dimensional (2D) microenvironment via polydopamine (pDA) chemistry and subsequent carboxymethyl chitosan (CMC) grafting to enhance the culture and osteogenic potential of hPSCs in vitro. The hPSCs including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) were successfully cultured on the peptides-decorated surface without Matrigel and ECM protein coating and underwent promoted osteogenic differentiation in vitro, determined from the alkaline phosphate (ALP) activity, gene expression, and protein production as well as calcium deposit amount. It was found that directed osteogenic differentiation of hPSCs was achieved through a peptides-decorated niche. This chemically defined and safe 2D microenvironment, which facilitates proliferation and osteo-differentiation of hPSCs, not only helps to accelerate the translational perspectives of hPSCs but also provides tissue-specific functions such as directing stem cell differentiation commitment, having great potential in bone tissue engineering and opening new avenues for bone regenerative medicine.
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CELL BIOLOGY AND TOXICOLOGY
·
2025
·Vol. 41
·期 1
·1-29
·
IF 5.9
Tian Sirui,Yu Haiyang,Yang Ruoxuan,Wang Heshi,Zhao Baohong,Wang Danning
Soft tissue injury (STI) is a prevalent condition that requires effective therapeutic approaches. The focus of this investigation was to elucidate the molecular mechanisms linked to the IGFBP3 protein in adipose-derived stem cells (ADSCs) for STI repair, utilizing single-cell multiomics technology and a 3D bioprinting model. Establishment of a mouse-based STI model facilitated the comparison of cellular compositions and communication variances between wounded and normal tissues through single-cell RNA sequencing (scRNA-seq). High-throughput transcriptomics and bioinformatics analysis pinpointed IGFBP3 as a key target in ADSCs related to STI repair. In vitro experiments assessed IGFBP3's effects on ADSCs' epithelial cell differentiation, proliferation, and migration using various assays and lentivirus transfection to manipulate IGFBP3 expression. A 3D bioprinting technique was used to create an ADSCs-IGFBP3 peptide self-assembling hydrogel scaffold, characterized by Fourier-transform infrared spectroscopy, X-ray diffraction, SEM, and TEM. The scaffold's efficacy was validated in an animal model. Results showed nine cell subtypes in both normal and injured tissues, with increased ADSCs in STI tissues exhibiting enhanced connectivity and interactions. RNA-seq analysis confirmed IGFBP3 as crucial for ADSCs and STI. In vitro and 3D bioprinting experiments, along with animal model validation, confirmed IGFBP3's role in STI repair. Upregulation of IGFBP3 in ADSCs promoted epithelial cell differentiation by enhancing ITGB1 expression, activating the ERK pathway to boost cell proliferation and migration. This study highlights IGFBP3's significant role in ADSCs for STI repair, providing potential molecular targets for developing new treatments. The findings offer valuable insights into IGFBP3's mechanisms, aiding in advancing STI therapeutic strategies. Graphical 1. IGFBP3 enhances ADSC function in STI repair by activating ITGB1 and ERK pathways. 2. High IGFBP3 expression promotes ADSC differentiation into epithelial cells, improving tissue regeneration. 3. Single-cell multiomics and 3D bioprinting validate IGFBP3’s role in advancing STI treatment. 4. Findings present IGFBP3 as a promising molecular target for clinical STI therapy.
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