BMC BIOTECHNOLOGY
·
2026
·
IF 4.8
Guan Junjie,Chen Xiaoqing,Cheng Jiaqi,Lu Yang,Chen Xiangdong
Severe inflammatory reactions and increased levels of reactive oxygen species (ROS) significantly worsen the degenerative progression of spinal cord injury (SCI). Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) can alleviate inflammation associated with SCI, although their yield is limited. Conversely, MSC-extruded nanovesicles (NVs) possess therapeutic potential and exhibit significantly higher levels than EVs. In this study, an ROS-nanoscaffold (RNS + NVs) was developed for the treatment of SCI. NVs were produced from MSCs via physical extrusion and incorporated into an ROS-nanoscaffold (RNS). RNS + NVs effectively scavenged and degraded ROS, enabling the responsive release of NVs. NVs inhibited pro-inflammatory changes and decreased IL-6 and TNF-α release from lipopolysaccharide-induced BV2 cells, demonstrating anti-inflammatory activity similar to that of EVs. Furthermore, NVs exhibited a more pronounced antioxidative effect than EVs and successfully mitigated oxidative stress-induced damage in H 2 O 2 -induced PC12 cells. Moreover, in SCI models, NV absorption is predominantly mediated by the microglia and neurons. RNS + NVs have shown synergistic benefits in modulating the adverse in vivo microenvironment during the acute stage, consequently creating a favorable setting for tissue healing, long-term locomotion, and alleviation of neuropathic pain. RNS + NVs demonstrated significant potential as antioxidant and anti-inflammatory agents in SCI.
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高影响因子
Discovery Medicine
·
2024
·Vol. 36
·期 186
·1420-1429
·
IF 2
Shimaa Saad El-Din,Basma Emad Aboulhoda,Amira Hassouna,Marwa M Shakweer,Mansour A Alghamdi,Doha Essam,Mohamed Essam,Nawaf A AlRakaf,Hanaa M Elzahed,Asmaa Selmy,Dina Sabry,Dina M Mekawy
Background: Bone marrow-derived mesenchymal stem cells (BM-MSCs) have recently attracted great attention due to their crucial anti-inflammatory and regenerative properties. This work aims to examine the curative impact of intra-articular injection of BM-MSCs-derived exosomes in ameliorating osteoarthritis (OA) progression in rats and to explore the interaction between circular RNA of Yes-associated protein 1 ( circYAP1 ) and microRNA-21 ( miRNA-21 ) in the rat knee joints. Methodology: Gene expression circYAP1 , miRNA-21 , toll-like receptor-7 ( TLR7 ), aggrecan, and collagen type II were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in the rat articular tissues. In addition, the Enzyme-linked immunosorbent assay (ELISA) technique was used to estimate the level of the inflammatory markers interleukin 4 (IL-4), interleukin 10 (IL-10), interleukin 1β (IL-1β), and tumor necrosis factor-alpha (TNF-α); and the oxidative markers glutathione (GSH), malondialdehyde (MDA) and total reactive oxygen species (ROS). Histopathological examination using Hematoxylin and Eosin (H&E) staining of the rat articular tissue was also performed along with an estimation of the articular cartilage thickness. Results: Our results showed that BM-MSCs-derived exosomes significantly elevated circYAP1 gene expression level ( p < 0.05) along with subsequent downregulation of miRNA-21 and TLR7 ( p < 0.05). These effects impacted the inflammatory milieu of rat articular surfaces, where there was a significant reduction ( p < 0.05) of the pro-inflammatory and oxidative markers with significantly increased production of the anti-inflammatory and antioxidative markers ( p < 0.05). Marked elevation in aggrecan and collagen type II gene expression was also found in the treated groups ( p < 0.05). Conclusion: Those data suggest that BM-MSCs-derived exosomes have a crucial role in mitigating OA symptoms and pathology progression and might be regarded as an effective as well as acceptable treatment option for OA.
研究领域:
再生医学
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干细胞生物学
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分子生物学
·
骨科
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DOI
PubMed
高影响因子
Journal of Tissue Engineering
·
2020
·
IF 5.352
Haotian Bai,Noh Kyu-Cheol,Zhonghan Wang,Yutao Cui,He Liu,Hou Liu,Yubin Feng,Yue Zhao,Quan Lin,Zuhao Li
A diabetic foot ulcer (DFUs) is a state of prolonged chronic inflammation, which can result in amputation. Different from normal skin wounds, various commercially available dressings have not sufficiently improved the healing of DFUs. In this study, a novel self-healing hydrogel was prepared by in situ crosslinking of N-carboxyethyl chitosan (N-chitosan) and adipic acid dihydrazide (ADH) with hyaluronic acid-aldehyde (HA-ALD), to provide a moist and inflammatory relief environment to promote stem cell proliferation or secretion of growth factors, thus accelerating wound healing. The results demonstrated that this injectable and self-healing hydrogel has excellent swelling properties, stability, and mechanical properties. This biocompatible hydrogel stimulated secretion of growth factors from bone marrow mesenchymal stem cells (BM-MSCs) and regulated the inflammatory environment by inhibiting the expression of M1 macrophages and promoting the expression of M2 macrophages, resulting in granulation tissue formation, collagen deposition, nucleated cell proliferation, neovascularization, and enhanced diabetic wound healing. This study showed that N-chitosan/HA-ALD hydrogel could be used as a multifunctional injectable wound dressing to regulate chronic inflammation and provide an optimal environment for BM-MSCs to promote diabetic wound healing.
研究领域:
生物医学工程
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组织工程
·
伤口愈合
·
糖尿病
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DOI
PubMed
高影响因子
Materials Today Advances
·
2022
·
IF 9.918
Siyong Gao,Yuxin Tang,Wei Sun,Zhixin Liu,Tianyu Zhao,Xiang Li,Tianlu Wang,Guiqing Liao,Tao Xu,Guangsen Zheng,Yujie Liang
Schwann cells (SCs)-based nerve guidance conduits (NGCs) is a promising strategy for repairing long-gap peripheral nerve injury (PNI). But the number of SCs is limited as terminally differentiated cells. Matrix stiffness is able to direct cell fate of stem cells. And nerve-special stiffness (NSS) may contribute to stem cells converting into SCs. However, the potential mechanisms remain uncertain. The present study aimed to elucidate whether the given NSS was able to promote mesenchymal stem cells (MSCs) trans -differentiating into Schwann cell-like cells (SCLCs), facilitating cell-based NGCs repairing PNI. Gelatin methacryloylate (GelMA) hydrogels with different stiffness were manufactured, and their roles in the trans -differentiation of MSCs into SCLCs were investigated in vitro study. The most favorable stiffness (0.9–2.9 kPa) for trans -differentiation and neurotrophic factors expression was confirmed by western blot and immunofluorescence assays. The reason might lie in softer stiffness stretched cell morphology, leading to up-regulation of PIEZO1 and then activating YAP nuclear translocation. As for in vivo study, multi-channel NGCs containing SCLCs were fabricated with extrusion-based bioprinting and then filled a 5 mm gap in sciatic nerve defect of SD rats. It turned out that GelMA-made NGCs with stiffness of 2.9 kPa achieved promising neurogenerative capacity, not only promoting recovering sensory and motor functions, but also improving myelinated nerve fiber regeneration. Our findings demonstrated that 0.9–2.9 kPa might be the desired mechanical strength inducing trans -differentiation into SCLCs via PIEZO1/YAP axis, and the 3D-printed GelMA NGCs combined with SCLCs could be a potential candidate for long-gap peripheral nerve injury.
研究领域:
生物医学工程
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组织工程
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神经科学
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干细胞生物学
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高影响因子
Advanced Materials Interfaces
·
2022
·Vol. 9
·期 12
·2102549
·
IF 6.389
Jiamin Zhang,Xuzhao He,Suya Lin,Xiaoyi Chen,Lingqing Dong,Jun Lin,Huiming Wang,Wenjian Weng,Kui Cheng
Piezoelectric biomaterials are considered to be able to mimic the electrophysiological microenvironment of natural bone tissue, thus enhancing the bone regeneration. However, the effects of heterogeneous electric potential gradient of piezoelectric biomaterials on their osteogenic performance still remain elusive, largely because of the challenge of harassing the distribution of electric potential gradient on the surface of piezoelectric biomaterials. This study controls the heterogeneous electric potential gradient on the CoFe 2 O 4 /poly(vinylidene fluoride-trifluoroethylene (CFO/P(VDF-TrFE)) membrane by using an alternatively positive–negative polarization processing on microscaled straight-stripe patterned indium tin oxide coated glass (ITO) electrodes. The potential gradient (Δ ζ ) on membranes can be controlled by the stripe width and polarization parameters. Interestingly, Δ ζ shows a significant influence on the cellular osteogenic potential of mesenchymal stem cells (MSCs) and the bone regeneration performance in vivo. The Δ ζ of 0.672 pm/(V*µm) shows the optimal osteogenic performance both in vitro and in vivo, which can be attributed to the boost of integrins α 5 β 1 expression as well as the orientated arrangement and contractility of the cytoskeletons via mechanotransduction signaling cascades. This work therefore shows the importance of heterogeneous electric potential and provides a novel strategy to accelerate the osteogenic performances of piezoelectric biomaterials.
研究领域:
生物医学工程
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生物材料科学
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组织工程
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细胞生物学
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DOI
高影响因子
Bioactive Materials
·
2024
·
IF 18
Yulu Yang,Xianhui Zhang,Yao Yang,Pengfei Gao,Wuzhe Fan,Tao Zheng,Weihu Yang,Yu Tang,Kaiyong Cai
Postmenopausal osteoporosis (PMOP) is a prevalent condition among elderly women. After menopause, women exhibit decreased iron excretion, which is prone to osteoporosis. To design a specific titanium implant for PMOP, we first analyze miRNAs and DNA characteristics of postmenopausal patients with and without osteoporosis. The results indicate that iron overload disrupts iron homeostasis in the pathogenesis of PMOP. Further experiments confirm that iron overload can cause lipid peroxidation and ferroptosis of MSCs, thus breaking bone homeostasis. Based on the findings above, we have designed a novel Ti implant coated with nanospheres of caffeic acid (CA) and deferoxamine (DFO). CA can bind on the Ti surface through the two adjacent phenolic hydroxyls and polymerize into polycaffeic acid (PCA) dimer, as well as the PCA nanospheres with the repetitive 1,4-benzodioxan units. DFO was grafted with PCA through borate ester bonds. The experimental results showed that modified Ti can inhibit the ferroptosis of MSCs in the pathological environment of PMOP and promote osseointegration in two main ways. Firstly, DFO was released under high oxidative stress, chelating with excess iron and decreasing the labile iron pool in MSCs. Meanwhile, CA and DFO activated the KEAP1/NRF2/HMOX1 pathway in MSCs and reduced the level of intracellular lipid peroxidation. So, the ferroptosis of MSCs is inhibited by promoting the SLC7A11/GSH/GPX4 pathway. Furthermore, the remained CA coating on the Ti surface could reduce the extracellular oxidative stress and glutathione level. This study offers a novel inspiration for the specific design of Ti implants in the treatment of PMOP.
研究领域:
生物材料
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骨科
·
材料科学
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细胞生物学
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生物医学工程
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DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2024
·Vol. 50
·期 1
·1-12
·
IF 3.7
Chen Hao,Zhao Haosen
Spinal cord injury (SCI) represents a severe trauma to the central nervous system, resulting in significant disability and imposing heavy burdens on families and society. Pathophysiological changes following SCI often trigger secondary injuries that complicate treatment. Bone marrow mesenchymal stem cells (BM-MSCs) have become a focal point of research due to their multifunctionality and self-renewal capabilities; however, their survival and neuroprotective functions are compromised in inflammatory environments. Resveratrol, known for its anti-inflammatory, anti-aging, and anti-oxidative stress properties, has been extensively studied. This research focuses on the anti-inflammatory effects of resveratrol post-SCI and its combined application with BM-MSCs to treat rat spinal cord injuries, exploring both efficacy and mechanisms. In vivo experiments investigated changes in the Sirt-1 signaling pathway post-SCI, while in vitro studies examined the effects of resveratrol on BM-MSCs under inflammatory conditions. The assessment included recovery of motor function, neuronal survival, and apoptosis in SCI rats treated with resveratrol alone or in combination with BM-MSCs. Findings reveal a correlation between Sirt-1 and inflammation signaling pathways post-injury. Resveratrol significantly enhanced the survival and efficacy of BM-MSCs in inflammatory environments by upregulating Sirt-1 and downregulating NF-κB and other inflammatory markers, thereby reducing apoptosis. Combined treatment with resveratrol and BM-MSCs showed superior outcomes in motor function recovery and neuronal survival compared to treatment with BM-MSCs alone. This study offers a novel therapeutic strategy for SCI, enhancing stem cell survival and function through modulation of the Sirt-1/NF-κB pathway, providing a theoretical and experimental foundation for clinical applications.
研究领域:
神经科学
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干细胞研究
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药理学
·
分子生物学
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PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Meifei Lian,Binbin Sun,Yu Han,Bin Yu,Weiwei Xin,Ruida Xu,Bing Ni,Wenbo Jiang,Yongqiang Hao,Xiuyin Zhang,Yi Shen,Zhiguang Qiao,Kerong Dai
Mesenchymal stem cells (MSCs) secrete paracrine trophic factors that are beneficial for tissue regeneration . In this study, a sponge-like scaffold with hierarchical and interconnected pores was developed using low-temperature deposition modeling (LDM) printing. Its effects on the cellular behavior, especially on the paracrine secretion patterns of MSCs, were comprehensively investigated. We found that compared with the scaffolds printed via the fused deposition modeling (FDM) technique, the LDM-printed sponges enhanced the adhesion, retention, survival, and ingrowth of MSCs and promoted cell-material interactions. Moreover, the paracrine functions of the cultured MSCs on the LDM-printed sponges were improved, with significant secretion of upregulated immunomodulatory, angiogenic, and osteogenic factors . MSCs on the LDM-printed sponges exert beneficial paracrine effects on multiple regenerative processes , including macrophage polarization, tube formation, and osteogenesis, verifying the enhanced immunomodulatory, angiogenic, and osteogenic potential. Further protein function assays indicated that focal adhesion kinase (FAK), downstream AKT, and yes-associated-protein (YAP) signaling might participate in the required mechanotransductive pathways, through which the hierarchical porous structures stimulated the paracrine effects of MSCs. In a rat distal femoral defect model, the MSC-laden LDM-printed sponges significantly promoted vascularized bone regeneration . The results of the present study demonstrate that the hierarchical porous biomimetic sponges prepared via LDM printing have potential applications in tissue engineering based on their cell-material interaction promotion and MSC paracrine function modulation effects. Furthermore, our findings suggest that the optimization of biomaterial properties to direct the paracrine signaling of MSCs would enhance tissue regeneration.
研究领域:
组织工程
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生物医学工程
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干细胞生物学
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再生医学
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DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Qihong Li,Chen Li,Jun Yan,Chunli Zhang,Yu Jiang,Xiantong Hu,Liwei Han,Li Li,Peng Wang,Lingzhou Zhao,Yantao Zhao
Repairing large bone defects remains a significant clinical challenge. Stem cell is of great importance in bone regeneration, and periosteum is rich in periosteal stem cell, which has a great influence on repairing bone defects. Bioengineered periosteum with excellent biocompatibility and stem cell homing capabilities to promote bone regeneration is of great clinical significance. The E7 peptide (EPLQLKM), which exhibits a specific affinity for mesenchymal stem cells (MSCs), is beneficial for modulating cellular functions. In this study, a unique microporous structured carboxymethyl chitosan/sodium alginate membrane with a proper mass ratio is developed by the addition of Poloxam 407 （P407）, which is then functionalized with the E7 affinitive peptide. This membrane, characterized by its microporous structure and E7 peptide functionalization (CSSA/P/E), not only demonstrated favorable mechanical properties, enhanced hydrophilicity, satisfactory biodegradation profile, and excellent biocompatibility, but also synergistically enhanced MSCs recruitment. It is found to promote the proliferation, spreading, and osteogenic differentiation of MSCs in vitro and to accelerate early periosteal regeneration, bone matrix deposition, and vascularization in vivo, leading to effective regeneration of critical-sized bone defects. Overall, this study presents a robust, cell and growth factor-free strategy for bioengineering periosteum, offering a potential solution for the challenging large size bone defects.
研究领域:
组织工程
·
生物材料
·
再生医学
·
干细胞生物学
·
骨科
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Kexin Zhang,Chenyu Zhang,Huanxin Zhou,Yan Yang,Yanzhen Wen,Xiangyu Jiao,Mingze Yao,Yongqiang Wen
Diabetic wounds that do not heal for a long time challenge global healthcare. Mesenchymal stem cell (MSC) therapy has positive significance in promoting diabetic wound healing. However, traditional MSC therapy involves exogenous MSCs, which brings many limitations and unsatisfactory treatment. Moreover, the maintenance of MSC viability and function is difficult because of the high level of reactive oxygen species (ROS) in diabetic wounds. Therefore, we developed a nanofibrous dressing to recruit and protect endogenous MSCs while avoiding the inherent disadvantages of exogenous MSCs. Ceria nanoparticles capable of ROS scavenging are integrated into the nanofibrous dressings, together with Apt19S, a DNA aptamer with affinity and selectivity for MSCs. In addition, the homogenization and freeze-drying technology give the nanofibrous dressings good elasticity, which protects the wound from external pressure. Further experiments in diabetic mice show that the dressing has excellent endogenous MSC recruitment and anti-inflammatory properties, thereby synergistically promoting diabetic wound healing. This study is expected to explore an efficient method of stem cell therapy, providing a new way to construct high-performance wound dressings.
研究领域:
生物医学工程
·
干细胞治疗
·
伤口愈合
·
纳米技术
·
糖尿病研究
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DOI
PubMed
高影响因子
ACS Nano
·
2019
·
IF 13.903
Jieni Fu,Xiangmei Liu,Lei Tan,Zhenduo Cui,Yufeng Zheng,Yanqin Liang,Zhaoyang Li,Shengli Zhu,Kelvin Wai Kwok Yeung,Xiaobo Feng,Xianbao Wang,Shuilin Wu
Using noninvasive stimulation of cells to control cell fate and improve bone regeneration by optical stimulation can achieve the aim of precisely orchestrating biological activities. In this study, we create a fast and repeatable photoelectric-responsive microenvironment around an implant using a bismuth sulfide/hydroxyapatite (BS/HAp) film. The unexpected increase of photocurrent on the BS/HAp film under near-infrared (NIR) light is mainly due to the depletion of holes through PO43– from HAp and interfacial charge transfer by HAp compared with BS. The electrons activate the Na+ channel of mesenchymal stem cells (MSCs) and change the cell adhesion in the intermediate environment. The behavior of MSCs is tuned by changing the photoelectronic microenvironment. RNA sequencing reveals that when photoelectrons transfer to the cell membrane, sodium ions flux and the membrane potential depolarizes to change the cell shape. Meanwhile, calcium ions fluxed and FDE1 was upregulated. Furthermore, the TCF/LEF in the cell nucleus began transcription to regulate the downstream genes involved in osteogenic differentiation, which is performed through the Wnt/Ca2+ signaling pathway. This research has created a biological therapeutic strategy, which can achieve in vitro remotely, precisely, and noninvasively controlling cell differentiation behaviors by tuning the in vivo photoelectric microenvironment using NIR light.
研究领域:
生物医学工程
·
组织工程
·
细胞生物学
·
光遗传学
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产品关联
DOI
PubMed
高影响因子
Small
·
2023
·
IF 13.3
Fangyu Qiao,Yang Zou,Binglin Bie,Yonggang Lv
Vascularization and innervation play irreplaceable roles in bone regeneration and bone defect repair. However, the reconstruction of blood vessels and neural networks is often neglected in material design. This study aims to design a genetically functionalized matrix (GFM) and enable it to regulate angiogenesis and neurogenesis to accelerate the process of bone defect repair. The dual small interfering RNA (siRNA)-polyvinylimide (PEI) (siRP) complexes that locally knocked down soluble vascular endothelial growth factor receptor 1 (sFlt-1) and p75 neurotrophic factor receptor (p75 NTR ) are prepared. The hybrid cell membrane (MM) loaded siRP is synthesized as siRNA@MMs to coat on polylactone (PCL) electrospun fibers for mimicking the natural bone matrix. The results indicates that siRNA@MMs could regulate the expression of vascular-related and neuro-related cytokines secreted by mesenchymal stem cells (MSCs). GFMs promote the expression of osteogenic differentiation through paracrine function in vitro. GFMs attenuates inflammation and promotes osseointegration by regulating the coupling of vascularization and innervation in vivo. This study uses the natural hybrid cell membrane to carry genetic material and assist in the vascularization and innervation function of two siRNA. The results present the significance of neuro-vascularized organoid bone and may provide a promising choice for the design of bone tissue engineering scaffold.
研究领域:
组织工程
·
生物医学工程
·
再生医学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
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