Stem Cell Reviews and Reports
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2022
·Vol. 18
·期 3
·1168-1180
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IF 6.692
Wang Jin,Xiong Minghao,Sun Qihao,Tan Wen-Song,Cai Haibo
The existing approaches of hematopoietic stem cells (HSCs) expansion in vitro were difficult to meet the needs of clinical application. While in vivo, HSCs efficiently self-renew in niche where they interact with three dimension extracellular matrix and stromal cells. Osteoblasts (OBs) are one of most significant stromal cells of HSCs niche. Here, we proposed a three-dimensional environment based on gallic acid grafted-chitosan ( 2c ) scaffold and OBs differentiated from human umbilical cord mesenchymal stem cells (HUMSCs) to recapitulate the main components of HSCs niche. The results of alkaline phosphatase staining and alizarin red staining demonstrated that HUMSCs were successfully induced into OBs. The results showed that the expansions of CD34 + cells, CD34 + CD38 − cells and CD34 + CD38 − CD45RA − CD49f + CD90 + cells (primitive hematopoietic stem cells, pHSCs) harvested from the biomimetic HSCs niche based on 2c scaffold and OBs ( IV) group were larger than those harvested from other three culture groups. Importantly, it was found that the CD34 + cells harvested from IV group had better secondary expansion capability and colony forming potential, indicating better self-renewal ability. In addition, the biomimetic HSCs niche based on 2c scaffold and OBs protected HSCs apoptosis and promoted HSCs division. Taken together, the biomimetic HSCs niche based on 2c scaffold and OBs was an effective strategy for ex vivo expansion of HSCs in clinical scale. Graphical abstract
研究领域:
生物医学工程
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干细胞生物学
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组织工程
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再生医学
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DOI
PubMed
高影响因子
GENE
·
2021
·
IF 3.688
Ming Deng,Ping Xie,Zhonghui Chen,Yan Zhou,Junqi Liu,Jianghua Ming,Jianwei Yang
Background Spinal cord injury (SCI) leads to severe motor and sensory dysfunctions. Neural stem cells (NSCs) transplantation therapy plays a positive role in functional recovery after SCI, but the effectiveness of this therapy is limited by inadequate differentiation ability of transplanted NSCs. Mammalian achaete-scute homologue-1 (Mash-1) has been reported to improve differentiation of NSCs. Thus, this study modified NSCs with Mash-1 to repair SCI. Methods NSCs isolated from rat embryo hippocampus were cultured and identified in vitro and further transfected with the lentiviral vectors (Lv-Mash-1). After establishing a SCI rat model, the rats were transplanted with Mash-1 modified NSCs, the histopathological changes of rat spinal cord were detected by hematoxylin-eosin (HE) staining, and the locomotor activity of rats was evaluated with the Basso, Beattie and Bresnahan (BBB) scale. The NSCs cultured in vitro or extracted from SCI rat spinal cord were identified by immunofluorescence (IF). Mash-1, β3-Tubulin, and NeuN expressions in those cells were determined by Western blotting and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Results NSCs isolated from rat embryo hippocampus were Nestin- and NeuN-positive. NSC transplantation modified by Mash-1 increased BBB score of SCI rats and promoted recovery in lesion site of SCI rats. Mash-1 overexpression also promoted β3-Tubulin and NeuN expressions in NSCs cultured in vitro or extracted from spinal cord of SCI rats. Conclusion Mash-1 overexpression promoted NSC differentiation into neurons, and further improved locomotor functional recovery of SCI rats.
研究领域:
神经科学
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干细胞研究
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再生医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PERIODONTOLOGY
·
2023
·
IF 4.3
Jing Ni,Mengdi Li,Chaolun Li,Zhe Zhong,Hongwei Xi,Yiqun Wu
Background : The aim of this study was to construct crosslinked polylysine-hyaluronic acid microspheres (pl-HAM) ladened with gingival mesenchymal stem cells (GMSCs) and explore its biologic behavior in soft tissue regeneration. Methods : The effects of the crosslinked pl-HAM on the biocompatibility and the recruitment of L-929 cells and GMSCs were detected in vitro. Moreover, the regeneration of subcutaneous collagen tissue, angiogenesis and the endogenous stem cells recruitment were investigated in vivo. We also detected the cell developing capability of pl-HAMs. Results : The crosslinked pl-HAMs appeared to be completely spherical-shaped particles and had good biocompatibility. L-929 cells and GMSCs grew around the pl-HAMs and increased gradually. Cell migration experiments showed that pl-HAMs combined with GMSCs could promote the migration of vascular endothelial cells significantly. Meanwhile, the GFP-GMSCs in the pl-HAM group still remain in the soft tissue regeneration area 2 weeks after surgery. The results of in vivo studies showed that denser collagen deposition and more angiogenesis-related indicator CD31 expression in the pl-HAMs+ GMSCs + GeL group compared to the pl-HAMs + GeL group. Immunofluorescence showed that CD44, CD90, CD73 co-staining positive cells surrounded the microspheres in both pl-HAMs + GeL group and pl-HAM + GMSCs + GeL group. Conclusions : The crosslinked pl-HAM ladened with GMSCs system could provide a suitable microenvironment for collagen tissue regeneration, angiogenesis and endogenous stem cells recruitment, which may be an alternative to autogenous soft tissue grafts for minimally invasive treatments for periodontal soft tissue defects in the future. This article is protected by copyright. All rights reserved
研究领域:
组织工程
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再生医学
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牙科科学
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生物材料
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-12
·
IF 3.9
Li Xinyue,Qin Sheng,Liao Xiaoyun,Li Yang,Liu Aimei
Mesenchymal’ stem cells (MSC) are widely used for transplantation to treat various diseases due to their strong immune regulatory and tissue repair abilities. Magnetic nanoparticles (MNPs) can be used to track transplanted MSC. However, the potential impact of the MNPs we developed on MSC function remains unclear. In this study, we treated MSC with poly-L-lysine (PLL)-modified MNPs (MSC-MNPs) at a concentration of 0.1 µg/µL to assess their effects on MSC. The results showed that there were no significant effects on cell morphology, differentiation potential, proliferation, apoptosis, or the cell cycle after MSC were treated with MNPs. Interestingly, further experiments revealed that MNPs significantly enhanced the migratory capacity of MSC. Bio-Plex analysis revealed that MNPs promoted the expression of anti-inflammatory cytokines while inhibiting the secretion of pro-inflammatory factors. Flow cytometry also detected a significant increase in the number of MSC subpopulations, including CD184⁺MSC, CD106⁺MSC, and CD55⁺MSC, after MNPs labeling, which was further supported by proteomic analysis. Moreover, MSC-MNPs promoted the phenotypic transition of reactive astrocytes from A1 to A2 after coculture with activated astrocytes. In conclusion, MNPs have no cytotoxic effects on MSC labeling and significantly enhance their anti-inflammatory functions, offering new possibilities for the clinical application of MSC.
研究领域:
纳米技术
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干细胞生物学
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免疫学
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神经科学
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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 MOLECULAR HISTOLOGY
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2025
·Vol. 56
·期 2
·1-15
·
IF 2.2
Hou Huailong,Qiu Zhengjun,Che Jingyi,Li Yanping,Sun Jingxuan,Zhang Weiwei,Ma Jinjie,Zhang Shuang,Li Mengdi,Niu Yumei,He Lina
Dental pulp stem cells (DPSCs), a subset of tooth-derived mesenchymal stem cells (MSCs), demonstrate significant promise in clinical stem cell therapy. However, prolonged in vitro expansion commonly results in compromised stemness, limiting therapeutic efficacy. Thus, maintaining the stemness of DPSCs during expansion and culture is a key challenge for regenerative medicine. In the current study, the impact of simulated microgravity (SMG) on DPSC stemness was investigated using the three-dimensional clinostat Cellspace-3D. After SMG treatment for 3 days, DPSCs demonstrated markedly enhanced replicative activity, proliferation efficiency, self-renewal capacity, and effective inhibition of the senescence process. Under specific differentiation induction conditions, DPSCs in the SMG group exhibited superior osteogenic, adipogenic, chondrogenic, and neural differentiation potentials. Additionally, DPSCs exhibited higher expression levels of the MSC surface markers Stro-1 and CD146 and stemness maintenance-related genes Oct4, Nanog, and Sox2 in the SMG group compared to those from the normal gravity (NG) group. To elucidate the potential molecular mechanisms by which SMG influences the stemness of DPSCs, transcriptome sequencing of total RNA was performed, and identified that differentially expressed genes (DEGs) are closely associated with the MAPK signaling pathway. Further verification experiments demonstrated that the MAPK/ERK signaling pathway was activated in the SMG group. In conclusion, SMG effectively maintains the stemness of DPSCs cultivated in vitro, and its mechanism of action may be associated with the activation of the MAPK/ERK signaling pathway.
研究领域:
干细胞生物学
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再生医学
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细胞生理学
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分子生物学
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转录组学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2023
·
IF 9.5
Hui Guo,Xu Peng,Xiangyu Dong,Jiangge Li,Chong Cheng,Qiang Wei
Bone regenerative biomaterials are essential in treating bone defects as they serve as extracellular matrix (ECM) mimics, creating a favorable environment for cell attachment, proliferation, and differentiation. However, the currently used bone regenerative biomaterials mostly exhibit high stiffness, which may lead to difficulties in degradation and thus increase the risk of foreign body ingestion. In this study, we prepared soft fibrous scaffolds modified with Zn-MOF-74 nanoparticles via electrostatic spinning. The soft fibers (only 1 kPa) permit remodeling under cellular adhesive force, optimizing the mechanical cues in the microenvironment to support cell adhesion and mechanosensing. In addition, the incorporation of Zn-MOF-74 nanoparticles enables the stable and sustained release of zinc ions, promoting stem cell mechanotransduction and osteogenic differentiation. Therefore, the hybrid soft fibers facilitate the regeneration of new bone in the rat femoral defect model, which provides a promising approach for regenerative medicine.
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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纳米技术
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生物力学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2020
·
IF 10.652
Jiezhou Wu,Gen Li,Tingjun Ye,Guanghua Lu,Runmin Li,Lianfu Deng,Lei Wang,Ming Cai,Wenguo Cui
Injection of cell-laden hydrogel microspheres is a minimally invasive method for tissue regeneration. However, microspheres are usually limited by structural heterogeneity, uneven size, low cell loading capacity, and poor cell survival rate. We devised a microfluidics synchronous cross-linked technology to obtain injectable homogenous porous microspheres of desired particle (50–400 μm) and pore (0–50 μm) size by adjusting the flow rate and concentration of gelatin methacrylamide (GelMA). The synchronous cross-linking controlled the strength of cross-linking and prevented fusion and uneven cross-linking. The freeze-dried microspheres of particle size 300 μm and pore size 50 μm rapidly adsorbed murine bone marrow-derived stem cells (BMSCs) and maintained their viability and osteogenic potential in vitro . In addition, the cell-loaded porous microspheres promoted tissue regeneration when injected locally into a murine bone defect model. Our results show that hydrogel microspheres generated by the microfluidics synchronous cross-linked technology are stable and biocompatible, and have strong regenerative potential when loaded with stem cells.
研究领域:
组织工程
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再生医学
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生物材料科学
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DOI
高影响因子
Scientific Reports
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2017
·Vol. 7
·期 1
·1-12
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IF 4.259
Wang Dong,Wang Aijun,Wu Fan,Qiu Xuefeng,Li Ye,Chu Julia,Huang Wen-Chin,Xu Kang,Gong Xiaohua,Li Song
Implanted biomaterials and biomedical devices generally induce foreign body reaction and end up with encapsulation by a dense avascular fibrous layer enriched in extracellular matrix. Fibroblasts/myofibroblasts are thought to be the major cell type involved in encapsulation, but it is unclear whether and how stem cells contribute to this process. Here we show, for the first time, that Sox10 + adult stem cells contribute to both encapsulation and microvessel formation. Sox10 + adult stem cells were found sparsely in the stroma of subcutaneous loose connective tissues. Upon subcutaneous biomaterial implantation, Sox10 + stem cells were activated and recruited to the biomaterial scaffold, and differentiated into fibroblasts and then myofibroblasts. This differentiation process from Sox10 + stem cells to myofibroblasts could be recapitulated in vitro . On the other hand, Sox10 + stem cells could differentiate into perivascular cells to stabilize newly formed microvessels. Sox10 + stem cells and endothelial cells in three-dimensional co-culture self-assembled into microvessels, and platelet-derived growth factor had chemotactic effect on Sox10 + stem cells. Transplanted Sox10 + stem cells differentiated into smooth muscle cells to stabilize functional microvessels. These findings demonstrate the critical role of adult stem cells in tissue remodeling and unravel the complexity of stem cell fate determination.
研究领域:
生物医学工程
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干细胞生物学
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组织工程
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再生医学
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DOI
PubMed
高影响因子
DEVELOPMENTAL CELL
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2020
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IF 10.092
Gang Du,Lishou Xiong,Xiaorong Li,Zhangpeng Zhuo,Xiaojun Zhuang,Zihua Yu,Lijian Wu,Danqing Xiao,Zhiming Liu,Minwen Jie,Xuehong Liu,Guanzheng Luo,Zheng Guo,Haiyang Chen
Summary Epithelial-repair-dependent mucosal healing (MH) is associated with a more favorable prognosis for patients with inflammatory bowel disease (IBD). MH is accomplished via repair and regeneration of the intestinal epithelium. However, the mechanism underlying MH is ill defined. We found a striking upregulation of peroxisomes in the injured crypts of IBD patients. By increasing peroxisome levels in Drosophila midguts, we found that peroxisome elevation enhanced RAB7-dependent late endosome maturation, which then promoted stem and/or progenitor-cell differentiation via modulation of Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT)-SOX21A signaling. This in turn enhanced ISC-mediated regeneration. Importantly, RAB7 and SOX21 were upregulated in the crypts of IBD patients. Moreover, administration of drugs that increased peroxisome levels reversed the symptoms of dextran sulfate sodium (DSS)-induced colitis in mice. This study demonstrates a peroxisome-mediated epithelial repair mechanism, which opens a therapeutic avenue for the enhancement of MH in IBD patients.
研究领域:
胃肠病学
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细胞生物学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Qiang Wang,Shiyou Li,Chen Xu,Xing Wang,Tian Yang,Chong Wang,Yuxuan Xiong,Zhijie Zhang,Xiangliang Yang,Zifu Li
High reactive oxygen species (ROS) levels provide a therapeutic opportunity to eradicate cancer stem cells (CSCs), a population of cells responsible for tumorigenesis, progression, metastasis, and recurrence. However, enhanced antioxidant systems in this population of cells attenuate ROS-inducing therapies. Here, we developed a nanoparticle-assisted combination therapy to eliminate CSCs by employing photodynamic therapy (PDT) to yield ROS while disrupting ROS defense with glutaminolysis inhibition. Specifically, we leveraged an oleic acid-hemicyanine conjugate (CyOA) as photosensitizer , a new entity molecule HYL001 as glutaminolysis inhibitor, and a biocompatible folic acid-hydroxyethyl starch conjugate (FA-HES) as amphiphilic surfactant to construct cellular and mitochondrial hierarchical targeting nanomedicine (COHF NPs). COHF NPs inhibited glutaminolysis to reduce intracellular ROS scavengers, including glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH), and to blunt oxidative phosphorylation (OXPHOS) for oxygen-conserved PDT. Compared to COLF NPs without glutaminolysis inhibitor, COHF NPs exhibited higher phototoxicity to breast cancer stem cells (BCSCs) both in vitro and in vivo . More importantly, we corroborated that marketed glutaminolysis inhibitors, such as CB839 and V9302, augment the clinically used photosensitizer (Hiporfin) for BCSCs elimination. This study develops a potent CSCs targeting strategy by combining glutaminolysis inhibition with PDT and provides significant implications for cancer therapy.
研究领域:
肿瘤学
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纳米技术
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药学
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治疗学
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产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2026
·
IF 14.6
Zitao Fan,Shiyou Li,Chen Xiao,Qiang wang,Zhijie Zhang,Ao hua,Qingqing Xu,Tian Yang,Jiayuan Li,Yue Pan,Baizhu Chen,Xiangliang Yang,Zhenwei Zou,Zifu Li
The metabolic plasticity of cancer stem cells (CSCs) enables them to adaptively switch between glycolysis, oxidative phosphorylation, and alternative fuels such as glutamine and fatty acids, promoting tumorigenesis and progression by ensuring survival under diverse environmental stresses. However, current therapeutic approaches targeting CSCs remain limited, particularly those relying on single metabolic interventions. By leveraging concurrent metabolic modulation and redox disruption to sensitize CSCs to cuproptosis, we prepared a polydopamine/hydroxyethyl starch-based nanoplatform (CH@PHF) for co-delivering copper-diethyldithiocarbamate (CuET) and HYL001. Specifically, HYL001 suppresses glutaminase (GLS) activity, thereby blocking glutamine metabolism and inhibiting glutathione (GSH) biosynthesis. This effect synergizes with CuET to collectively amplify oxidative stress in CSCs. Furthermore, the combination of HYL001 and CuET significantly elevates intracellular copper levels, particularly the cuprous form (Cu + ), thereby sensitizing CSCs to cuproptosis. This combined treatment effectively inhibits tumor growth and metastasis by targeting and eradicating breast cancer stem cells (BCSCs), offering a promising avenue for tumor therapy.
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Long Yuan,Xiaowei Qi,Gaoping Qin,Qi Liu,Fan Zhang,Yong Song,Jun Deng
Nanoparticles are nanocrystals with complex facets and defective structures that do not adopt an idealised shape. Various physicochemical parameters of nanoparticles, such as surface composition, size, and stiffness, can regulate differentiation in mesenchymal stem cells (MSCs), but the influence of shapes with many edges and corner regions has not been investigated. Herein, we investigated the effects of two gold nanostructures modified with 11-mercaptoundecanoic acid, namely gold nanocubes (MUA-AuNCs) and nanooctahedras (MUA-AuNOs), on viability and differentiation in rat bone marrow MSCs (bMSCs). Analysis of cytotoxicity and proliferation demonstrated good biocompatibility, with concentrations <100 μ g·mL −1 not significantly different from untreated controls. Alkaline phosphatase activity and Alizarin Red S staining revealed weaker potential for bMSCs to differentiate into osteoblasts following treatment with both low (5 μ g·mL −1 ) and high (25 μ g·mL −1 ) concentrations of the gold nanostructures. By contrast, Oil Red O staining showed that both nanostructures enhanced adipogenic differentiation, and upregulated peroxisome proliferator-activated receptor gamma (PPARγ) and fatty acid binding protein-4 (Fabp4) expression at both mRNA and protein levels. The effects on differentiation were both structure- and dose-dependent; MUA-AuNOs were more effective for enhancing adipogenic differentiation and weakening osteogenic differentiation, possibly due to generating higher levels of reactive oxygen species (ROS). These findings lay the foundation for using these nanoparticles as ex vivo labels in MSC-based imaging and therapy.
研究领域:
纳米技术
·
干细胞生物学
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材料科学
·
细胞工程
✓ 已验证
DOI
PubMed
高影响因子
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