Materials Today Bio
·
2025
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IF 10.2
Chen Wei,Xinyu Sun,Lijuan Gao,Yue Wang,Fantao Lin,Yao Du,Xiaoyu Zhao,Wei Gao,Jingkun Bai
Breast cancer stem cells (BCSCs) drive tumor formation and growth via self-renewal, differentiation, and high tumorigenic potential, and the persistence of BCSCs is an important cause of treatment failure in patients with breast cancer. In addition, the tumor microenvironment promotes the maintenance of BCSC stemness, inhibits immune cell activity, and forms an immune escape “barrier”. In this study, we developed an amphiphilic peptide nanocarrier system, PA/Pep1, with an RGD-targeting sequence. The delivery system simultaneously encapsulates the hydrophobic drugs paclitaxel (PTX) and all-trans retinoic acid (ATRA) and releases them in response to low pH in the tumor microenvironment. PA/Pep1 causes apoptosis in breast cancer cells, induces the differentiation of BCSCs and inhibits their expression, thus enhancing the killing effect of PTX. In breast cancer, PA/Pep1 effectively alleviates immune evasion by modulating transforming growth factor-β (TGF-β) and interleukin-6 (IL-6), thereby reducing the expression of programmed cell death-ligand 1 (PD-L1). Importantly, the transformation of the nanosystems into forms with high aspect ratios under acidic conditions effectively reduced drug efflux and extended the duration of drug action. In conclusion, the combination of stem cell therapy and immunotherapy, as well as the development of novel deformable amphiphilic peptide nanocarrier systems, provides new possibilities for breast cancer treatment.
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PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2025
·
IF 4.3
Yujia Wang,Hongbo Zhang,Jie Yu,Jin Jing,Zhaojiang Fu,Yuanping Hao,Qihang Huang,Ruibin Ma,Yingjie Xu,Yingtao Wu
Background Chronic periodontitis is a prevalent inflammatory and destructive oral disease, and its primary treatment is to control the development of inflammation and promote the regeneration of periodontal tissue. Psoralen (Pso) has been shown to promote the osteogenic differentiation of periodontal ligament stem cells (PDLSCs), suggesting its potential as a therapeutic agent for osteogenic regeneration. Methods Network pharmacology and transcriptomic sequencing were exploited to screen target genes of Pso in PDLSCs, lentiviruses were employed to interfere with the target gene, and RT-qPCR was conducted to assess the expression levels of osteogenesis-related factors. Pso-loaded mesoporous polydopamine (MPDA-Pso) nanoparticles were constructed and evaluated in vitro , and in vivo osteogenesis was assessed in rats with alveolar bone defects. Results Network pharmacology analysis revealed that the mammalian target of rapamycin (mTOR) was a potential target of Pso, and Pso significantly modulated the expression levels of mTOR in PDLSCs and markedly enhanced osteogenic differentiation. However, Pso did not significantly alter osteogenesis-related genes in PDLSCs after mTOR-inhibitor treatment. We also confirmed that MPDA-Pso nanoparticles promoted the expression of osteogenesis-related genes in PDLSCs; and compared with the control group, observed that the mass of new bone was augmented in the MPDA-Pso group. Conclusion Pso was shown to promote the osteogenic differentiation of PDLSCs, and we postulate that this differentiation was facilitated in the LPS-induced inflammatory microenvironment via inhibition of the autophagy-related mTOR-signaling pathway. Additionally, the MPDA-Pso nanoparticles we developed promoted osteogenesis.
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PubMed
高影响因子
INTERNATIONAL DENTAL JOURNAL
·
2025
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IF 3.7
Chenxuan Shu,Yu Luo,Ye Liu,Junnan Wang,Qiang Qin,Ziwei Li,Jieying Situ,Xiaojing Liu,Xiangying Wang,Yan He,Qingsong Ye
Introduction and aims Temporomandibular joint osteoarthritis (TMJ-OA) is characterized by cartilage destruction and pain. Although mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have shown therapeutic efficacy, their clinical translation is hampered by low yield and batch-to-batch variability. Recent studies indicate that intracellular vesicles (IVs) can be harvested at markedly higher quantities than EVs while displaying comparable biological profiles. Therefore, this study directly compared high-yield dental pulp stem cell-derived intracellular vesicles (DPSC-IVs) with conventional dental pulp stem cell-derived extracellular vesicles (DPSC-EVs) in terms of their ability to regenerate cartilage matrix and relieve pain in TMJ-OA. Methods Following characterization of DPSC-IVs and DPSC-EVs, we first evaluated their effects on the proliferation and migration of rat mandibular condylar chondrocytes (MCCs) using endocytic tracing, CCK-8 assays, and Transwell migration assays. Subsequently, an in vitro inflammation model was established using IL-1β, and Western blot analysis and RT-qPCR were employed to investigate their regulatory effects on cartilage matrix synthesis and inflammatory pathways. Next, an in vivo TMJ-OA model was constructed using sodium monoiodoacetate (MIA). The therapeutic efficacy of the two vesicles on subchondral bone remodelling and condylar cartilage matrix regeneration was multidimensionally validated through micro-CT, RT-qPCR, Western blotting, immunofluorescence and immunohistochemistry staining. Furthermore, their underlying molecular mechanisms for alleviating joint pain were elucidated. Results At the same therapeutic concentration, both DPSC-IVs and DPSC-EVs markedly enhanced MCCs proliferation and migration and suppressed IL-1β-induced cartilage matrix breakdown and inflammatory gene expression. In a rat TMJ-OA model, they equivalently repaired MIA-induced subchondral bone and condylar cartilage damage and significantly attenuated pain via inhibition of the ERK-CREB-CGRP pathway. Conclusion DPSC-IVs, with higher yield and simpler extraction, deliver therapeutic efficacy comparable to DPSC-EVs, offering a more clinically feasible strategy for TMJ-OA treatment.
研究领域:
干细胞治疗
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再生医学
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骨科
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口腔颌面外科
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分子生物学
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2025
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IF 6.7
Jiafeng Wang,Daijie Xie,Xiaozhang Qu,Tian Li,Xiuping Meng,Zhimin Zhang,Yongdong Jin,Guohua Qi
Mitochondrial fusion protein 2 (Mfn2) as a molecular gatekeeper in mitochondria plays a momentous role in regulating mitochondrial morphology and function to further influence cell behavior. However, ultrasensitive and in situ measurement of low-abundance Mfn2 at the single-cell level remains a challenge, especially during external stress. Herein, an ultrasensitive and “turn-on”-type immunoassay platform for analysis of Mfn2 expression at the single-cell level during the dental pulp stem cell (DPSC) differentiation process was exploited through surface-enhanced Raman spectroscopy (SERS) as a readout modality. In this system, the detection sensitivity of Mfn2 is markedly enhanced through the generation of gap-plasmon “hot spots” caused by the biocoded SERS nanoprobes consisting of AuNPs and AgNPs following the affinity binding of Mfn2. The developed SERS immunoassay exhibited a wide linear relationship for Mfn2, ranging from 0.5 ng/mL to 5 μg/mL. Notably, the biocoded plasmonic nanoprobes reacting with Mfn2 can self-assemble to form an SERS immunoassay biosensor within single cells, which enabled sensitive measurement of Mfn2 expressions during the DPSC differentiation process evoked by electric-impulse stimulation (EIS). Mechanistically, the Mfn2 expression within DPSCs showed palpable downregulation during the EIS-induced differentiation process. The work revealed at the single-cell level a previously unknown role of Mfn2 in DPSC differentiation during the EIS process. The developed SERS immunoassay sensing platform is promising for the early diagnosis of diseases associated with Mfn2.
研究领域:
生物医学工程
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分析化学
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细胞生物学
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纳米技术
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干细胞研究
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PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2025
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IF 3.6
Yuanqing Niu,Hengrui Chang,Jiaxin Xu
Mesenchymal stem cells (MSCs)-derived therapy has surfaced as a viable approach for addressing spinal cord injury (SCI). The unfavorable milieu of SCI significantly impairs the paracrine and survival function of implanted MSCs, hence greatly restricting the therapeutic efficacy of this method. We present a zinc-based nanoenzyme (ZnNZs)-combined in situ forming thermoresponsive hydrogels (ZnNZ-HGL) that facilitate dual improvement of MSCs paracrine and viability effects, resulting in highly effective spinal cord reconstruction. The sol-gel transitions characteristic of ZnNZ-HGL at the physiological milieu guarantees consistent distribution of HGL in damaged spinal cord tissue. Our findings indicate that ZnNZ-HGL markedly enhances the survivability of MSCs within the milieu by mitigating oxidative stress (OS) and, crucially, stimulates the release of MSCs’ angiogenic factors. The interplay among the oxidative stress-mitigating properties of ZnNZs influence of MSC enhances nerve healing, angiogenesis, and functional recovery following SCI, presenting a promising approach for MSCs-derived SCI treatment.
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高影响因子
FASEB JOURNAL
·
2025
·Vol. 39
·期 24
·e71350
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IF 4.2
Shuwei Huang,Qinyao Zhang,Meijiu Zhang,Xiaoqian Liu,Mingzhu Liu,Jun Sun,Hemin Nie,Lei Lei
Traditional monolayer cultures of stem cells from the apical papilla (SCAP) fall short in their ability to replicate the anatomical organization of SCAP and often fail to provide high-quality SCAP suitable for dental root regeneration. This study aimed to employ agarose-based low-adhesion plates to induce the spontaneous formation of SCAP spheroids and disclose the biological impacts of SCAP in forming papilla-like structures in vivo. Compared with monolayer-cultured SCAP, spheroid-cultured SCAP exhibited enhanced in vitro and in vivo odontoblastic differentiation potentials. RNA sequencing identified the importance of N-cadherin downregulation in enhancing the odontoblastic differentiation potential of SCAP in spheroids compared with monolayer-cultured SCAP. Furthermore, N-cadherin knockdown in vitro significantly upregulated the β-catenin signaling pathway, further promoting SCAP odontoblastic differentiation. SCAP cultured on agarose-based plates spontaneously form spheroids and undergo odontoblastic differentiation through N-cadherin downregulation, offering new insights into SCAP-mediated dentin regeneration. Graphical (A) RNA-seq revealed that spheroid cultures downregulate N-cadherin of SCAP. (B) N-cadherin sequesters β-catenin at cell membrane adhesion sites and interacts with Wnt co-receptors LRP5/6, thereby promoting β-catenin degradation.
研究领域:
牙科干细胞生物学
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再生牙医学
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细胞分化
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分子信号传导
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DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2025
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IF 7.9
Jingxia Chen,Jing Xu,Huixin Lv,Jiaxin Luo,Zhen Ci,Yangfan Pei,Yihan Wang,Xiuyu Liu,Sicong Ren,Sheng Chen,Siyu Chen,Ting Zhu,Jingjie Zhai,Yanmin Zhou
Jawbone defects pose significant challenges for oral implantation and restoration. Guided bone regeneration is the most common strategy for bone augmentation. However, inadequate efficiency of osteogenesis remains a persistent issue. Periosteum serves as a potential source of osteogenesis, but insufficient mesenchymal stem cells (MSCs) in periosteum often exist due to the lack of initial bone support. Inadequate blood supply near the submembranous osteogenic region also impedes the osteogenesis process. This paper proposes a dual cross-linked natural protein-derived hydrogel, GelMA-fibrinogen/NELL-1(GFN), which optimizes both physical and biological factors to stabilize the elevated maxillary sinus membrane (MSM) (an anatomical structure involved in osteogenesis in maxillary posterior dental region, resembling periosteum) and support the osteogenic space. The results showed stem cells derived from the membrane could migrate to GFN and exhibit robust proliferation capability. Under osteogenic induction, the adequately expanded MSM-derived MSCs enhanced osteogenic differentiation under the synergetic guidance of fibrinogen and Nell-1 through TGF-β/HIF-1α/β-catenin signaling pathway. In vivo experiments showed that GFN could promote bone formation with double-layered cortical bone structures in maxillary sinus region, which provides a new direction for construction of bone grafting materials.
研究领域:
生物材料
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组织工程
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再生医学
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口腔种植学
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干细胞生物学
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高影响因子
eLife
·
2019
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IF 7.551
Xuefei Yan,Beibei Tang,Biao Chen,Yongli Shan,Huajun Yang,Reproducibility Project: Cancer Biology,Elizabeth Iorns,Rachel Tsui,Alexandria Denis,Nicole Perfito,Timothy M Errington
As part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Li et al., 2015), that described how we intended to replicate selected experiments from the paper ‘The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44’ (Liu et al., 2011). Here we report the results. We found the microRNA, miR-34a, was expressed at twice the level in CD44+ prostate cancer cells purified from xenograft tumors (LAPC4 cells) compared to CD44- LAPC4 cells, whereas the original study reported miR-34a was underexpressed in CD44+ LAPC4 cells (Figure 1B; Liu et al., 2011). When LAPC4 cells engineered to express miR-34a were injected into mice, we did not observe changes in tumor growth or CD44 expression; however, unexpectedly miR-34a expression was lost in vivo. In the original study, LAPC4 cells expressing miR-34a had a statistically significant reduction in tumor regeneration and reduced CD44 expression compared to control (Figure 4A and Supplemental Figures 4A,B and 5C; Liu et al., 2011). Furthermore, when we tested if miR-34a regulated CD44 through binding sites in the 3’UTR we did not find a statistically significant difference, whereas the original study reported miR-34a decreased CD44 expression that was partially abrogated by mutation of the binding sites in the CD44 3’UTR (Figure 4D; Liu et al., 2011). Finally, where possible, we report meta-analyses for each result.
研究领域:
肿瘤学
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分子生物学
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癌症生物学
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DOI
PubMed
高影响因子
Nature Communications
·
2025
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IF 15.7
Haopeng Lin,Xin Liu,Feng Zhang,Deqi Chen,Xiaoxiao Xie,Qifei Dong,Jiawei Yan,Jiaxiang Yin,Zirong Bi,Zhihua Dou,Yingling Jiang,Kuo Jiang,Tongran Zhang,Peng Xue,Wei Peng,Lihua Chen,Tao Xu,Zonghong Li,Yanying Guo,Huisheng Liu
Human stem cell-derived β (SC-β) cells still exhibit limited glucose response required for insulin secretion due to glycolytic bottlenecks, yet how these metabolic abnormalities impact glucose response and functional maturation of SC-β cells remains unclear. In this study, we identify a metabolic checkpoint located at PEP accumulation that impedes the functional maturation, which is rescued by restoration of pyruvate kinase M1 ( PKM1 ). Glucose-tracing metabolomics in human stem cell-derived islets reveal abnormal glycolytic PEP accumulation at resting condition, associated with impaired calcium response and insulin secretion upon high glucose or glycolytic metabolite stimulation. Mechanistically, elevated PEP significantly raises intracellular basal calcium levels and downregulates expression of genes involved in TCA cycle as elucidated by single cell transcriptomics. Furthermore, the activity of pyruvate kinase, which metabolizes PEP, is notably reduced due to low PKM1 expression. Overexpression of PKM1 alleviates PEP accumulation, restores TCA-related gene expression, and enhances glucose-stimulated calcium responses and insulin secretion. Together, our findings reveal a critical role of PKM1-regulated PEP metabolism in SC-β cell functional maturation and highlight the importance of metabolic reprogramming for advancing stem cell-based therapies for diabetes. Human stem cell–derived β cells accumulate high basal PEP, which disrupts glucose-stimulated insulin release. Restoring PKM1 lowers basal PEP and improves glucose responses, advancing the maturation of stem cell–derived islets for diabetes therapy.
研究领域:
糖尿病研究
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干细胞生物学
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代谢学
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再生医学
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细胞生理学
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DOI
PubMed
高影响因子
CELL PROLIFERATION
·
2021
·Vol. 54
·期 7
·e13043
·
IF 6.831
Zhi-Hu Zhao,Xin-Long Ma,Bin Zhao,Peng Tian,Jian-Xiong Ma,Jia-Yu Kang,Yang Zhang,Yue Guo,Lei Sun
Objectives Large bone defects are a common, debilitating clinical condition that have substantial global health and economic burden. Bone tissue engineering technology has become one of the most promising approaches for regenerating defective bones. In this study, we fabricated a naringin-inlaid composite silk fibroin/hydroxyapatite (NG/SF/HAp) scaffold to repair bone defects. Materials and Methods The salt-leaching technology was used to fabricate the NG/SF/HAp scaffold. The cytocompatibility of the NG/SF/HAp scaffold was assessed using scanning electron microscopy, live/dead cell staining and phalloidin staining. The osteogenic and angiogenic properties were assessed in vitro and in vivo. Results The porous NG/SF/HAp scaffold had a well-designed biomimetic porous structure with osteoinductive and angiogenic activities. A gene microarray identified 854 differentially expressed genes between human umbilical cord-derived mesenchymal stem cells (hUCMSCs) cultured on SF-nHAp scaffolds and cells cultured on NG/SF/HAp scaffolds. The underlying osteoblastic mechanism was investigated using hUCMSCs in vitro. Naringin facilitated hUCMSC ingrowth into the SF/HAp scaffold and promoted osteogenic differentiation. The osteogenic and angiogenic capabilities of cells cultured in the NG/SF/HAp scaffold were superior to those of cells cultured in the SF/HAp scaffold. Conclusions The data indicate the potential of the SF/HAp composite scaffold incorporating naringin for bone regeneration.
研究领域:
组织工程
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生物医用材料
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干细胞生物学
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骨再生
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DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2020
·Vol. 11
·期 1
·1-15
·
IF 5.116
Zhao Yan,Ma Jiao,Yi Peiye,Wu Jun,Zhao Feiyan,Tu Wan,Liu Wenjing,Li Tianda,Deng Yan,Hao Jie,Wang Hongmei,Yan Long
Background Premature ovarian insufficiency (POI) is an ovarian dysfunction that seriously affects a woman’s physiological health and reproduction. Mesenchymal stem cell (MSC) transplantation offers a promising treatment option for ovarian restoration in rodent POI models. However, the efficacy and mechanism of it remain unclear.Methods POI mice model was generated by cyclophosphamide and busulfan, followed with the treatment of tail-vein injection of the human umbilical cord mesenchymal stem cells (hUCMSCs). Maternal physiological changes and offspring behavior were detected. To reveal the pathogenesis and therapeutic mechanisms of POI, we first compared the metabolite profiles of healthy and POI ovarian tissues using untargeted metabolomics analyses. After stem cell therapy, we then collected the ovaries from control, POI, and hUCMSC-treated POI groups for lipid metabolomics and pseudotargeted metabolomics analysis.Results Our results revealed remarkable changes of multiple metabolites, especially lipids, in ovarian tissues after POI generation. Following the transplantation of clinical-grade hUCMSCs, POI mice exhibited significant improvements in body weight, sex hormone levels, estrous cycles, and reproductive capacity. Lipid metabolomics and pseudotargeted metabolomics analyses for the ovaries showed that the metabolite levels in the POI group, mainly lipids, glycerophospholipids, steroids, and amino acids changed significantly compared with the controls’, and most of them returned to near-healthy levels after receiving hUCMSC treatment. Meanwhile, we also observed an increase of monosaccharide levels in the ovaries from POI mice and a decrease after stem cell treatment.Conclusion shUCMSCs restore ovarian function through activating the PI3K pathway by promoting the level of free amino acids, consequently improving lipid metabolism and reducing the concentration of monosaccharides. These findings provide potential targets for the clinical diagnosis and treatment of POI.
研究领域:
生殖生物学
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干细胞治疗
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代谢组学
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内分泌学
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2022
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IF 5.395
He Zhang,Xiaoming Fu,Siqi Zhang,Qian Li,Yang Chen,Hao Liu,Wen Zhou,Shicheng Wei
The use of human bone marrow mesenchymal stem cells (hBMSCs) to regenerate and repair bone tissue defects is a complex research field of bone tissue engineering; nevertheless, it is a hot topic. One of the biggest problems is the limited survival and osteogenic capacity of the transplanted cells within the host tissue. Even for hBMSCs with their low immunogenicity, the body will still cause a local immune-inflammatory response directed against the allogeneic cells and thereby reduce the activity of the transplanted cells. Even in the case of successful transplantation, the lack of vascularization at the transplantation site makes it difficult for the transplanted cells to exchange nutrients and metabolic wastes that ultimately affects bone regeneration. In this study, we covalently modified alginate with RGD and QK peptides that were injected subcutaneously into immunocompetent mice. Histological analysis, as well as ELISA techniques, proved that this method is able to provide bioactive stem cell transplant beds containing functionalized biomaterials and vascularized surrounding tissues. Inflammation-related factors, such as IL-2, IL-6, TNF-α, and IFN-γ, around the cell graft beds decreased with time and were lowest at the second week. Then, the hBMSCs were injected into the cell transplantation beds intended to form vascularized bonelike tissues that were evaluated by micro-computed tomography (Micro CT), histological, and immunohistochemical analyses. The results showed that the expression of osteogenesis-related proteins RUNX2, COL1A1, and OPN, as well as the expression of angiogenic factor vWF and cartilage-related protein COL2A1 were significantly upregulated in the hBMSC-derived osteogenic tissue. These results suggest that the stem cell transplantation strategy by constructing bioactive cell transplant beds is effective to enhance the bone regeneration capacity of hBMSCs and holds great potential in bone tissue engineering.
研究领域:
组织工程
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干细胞生物学
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生物材料科学
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免疫学
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再生医学
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DOI
PubMed
高影响因子
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