JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-17
·
IF 9.429
Lin Yuejun,Zhou Hui-chao,Chen Ningbo,Ren Yaguang,Gao Rongkang,Li Qiaojia,Deng Yiwen,Han Xuejiao,Zhang Xiaoran,Xiang Andy Peng,Guo Bing,Liu Chengbo,Ren Jie
Background Therapy with genetically modified mesenchymal stem cells (MSCs) has clinical translation promise. Optimizing the targeting migratory ability of MSCs relies on accurate imaging of the distribution and extravasation kinetics of MSCs, and the corresponding imaging results could be used to predict therapeutic outcomes and guide the optimization of the treatment program. Among the different imaging modalities, second near-infrared (NIR-II) optical-resolution photoacoustic microscopy (OR-PAM) has merits, including a fine resolution, a deep penetration, a high sensitivity, and a large signal-to-background ratio. It would be an ideal candidate for precise monitoring of MSCs, although it has not been tested for this purpose so far. Results Penetrating peptide-decorated conjugated polymer nanoparticles (TAT-CPNPs) with strong NIR-II absorbance were used to label chemokine-receptor genetically modified MSCs, which were subsequently evaluated under intravital NIR-II OR-PAM regarding their targeting migratory ability. Based on the upregulation of chemokine (C-X-C motif) ligand 10 in the inflamed ears of contact hypersensitivity mice, MSCs with overexpression of corresponding receptor, chemokine (C-X-C motif) receptor 3 (Cxcr3) were successfully generated (MSC Cxcr3 ). TAT-CPNPs labeling enabled NIR-II photoacoustic imaging to discern MSC Cxcr3 covered by 1.2 cm of chicken breast tissue. Longitudinal OR-PAM imaging revealed enhanced inflammation-targeting migration of MSC Cxcr3 over time attributed to Cxcr3 gene modification, which was further validated by histological analysis. Conclusions TAT-CPNPs-assisted NIR-II PA imaging is promising for monitoring distribution and extravasation kinetics of MSCs, which would greatly facilitate optimizing MSC-based therapy. Graphical Abstract
研究领域:
干细胞生物学
·
成像科学
·
分子生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2021
·
IF 6.684
Deng Moyuan,Tan Jiulin,Dai Qijie,Luo Fei,Xu Jianzhong
The positive role of macrophages in the osteogenesis of mesenchymal stem cells (MSCs) has been a recent research focus. On the other hand, MSCs could carefully regulate the paracrine molecules derived from macrophages. Human umbilical cord mesenchymal stem cells (hucMSCs) can reduce the secretion of inflammatory factors from macrophages to improve injury healing. hucMSC-derived extracellular matrix (hucMSC-ECM) has the similar effect to hucMSCs, which could combat the inflammatory response of macrophages. Additionally, MSC-derived extracellular matrix also enhanced bone regeneration by inhibiting osteoclastic differentiation of monocyte/macrophage lineage. However, whether hucMSC-ECM could improve bone formation by guiding macrophage-induced osteogenic differentiation of MSCs is unknown. Here, we present decalcified bone scaffolds modified by hucMSC-derived extracellular matrix (DBM-ECM), which maintained multiple soluble cytokines from hucMSCs, including macrophage migration inhibitory factor (MIF). Compared with DBM, the DBM-ECM scaffolds induced bone formation in an improved heterotopic ossification model of severe combined immunodeficiency (SCID) mice in a macrophage-dependent manner. Macrophages cocultured with DBM-ECM expressed four osteoinductive cytokines (BMP2, FGF2, TGFβ3 and OSM), which were screened out by RNA sequencing and measured by qPCR and western blot. The conditioned medium from macrophages cocultured with DBM-ECM improved the osteogenic differentiation of hBMSCs. Furthermore, DBM-ECM activated CD74/CD44 (the typical MIF receptors) signal transduction in macrophages, including phosphorylation of P38 and dephosphorylation of c-jun. On the other side, the inhibitory effects of the DBM-ECM scaffolds with a deficient of MIF on osteogenesis in vitro and in vivo revealed that macrophage-mediated osteogenesis depended on MIF/CD74 signal transduction. The results of this study indicate that the coordinated crosstalk of macrophages and MSCs plays a key role on bone regeneration, with an emphasis on hucMSC-ECM constructing a macrophage-derived osteoinductive microenvironment.
研究领域:
组织工程
·
再生医学
·
免疫学
·
细胞生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
·
2024
·Vol. 57
·期 4
·604
·
IF 3.3
Xuewei Li,Jinghui Feng,Haiqin Cheng,Ning Jin,Shanshan Jin,Zhizhen Liu,Jun Xu,Jun Xie
Liver fibrosis is a critical stage in the progression of various chronic liver diseases to cirrhosis and liver cancer. Early inhibition of liver fibrosis is crucial for the treatment of liver disease. Hepatectomy, a common treatment for liver-related diseases, promotes liver regeneration. However, in the context of liver fibrosis, liver regeneration is hindered. Many studies have shown that mesenchymal stem cells (MSCs) can promote liver regeneration after partial hepatectomy (PH). However, there are few reports on the impact of MSC therapy on liver regeneration post-PH in the context of hepatic fibrosis. The objective of this study is to examine the impact of MSCs on liver regeneration following PH in the fibrotic liver and uncover the related molecular mechanisms. This study reveals that MSC therapy significantly enhances liver function and mitigates liver inflammation after PH in the context of hepatic fibrosis. MSCs also significantly promote liver regeneration and alleviate liver fibrosis. In addition, this study identifies the role of MSCs in promoting liver regeneration and alleviating liver fibrosis via the activation of Wnt/β-catenin signaling. The combination of MSCs with hepatectomy may offer a novel approach for the treatment of liver fibrotic diseases.
研究领域:
医学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Yinjuan Lv,Chenggong Yu,Xiaodi Li,Hongying Bao,Shaoshuai Song,Xiaoling Cao,Haixia Lin,Jie Huang,Zhijun Zhang
Mesenchymal stem cell (MSC) transplantation is emerging as a promising approach in the treatment of idiopathic pulmonary fibrosis (IPF), while it is still impeded by several challenges, including unsatisfactory treatment outcomes due to the poor survival of transplanted MSCs, and the lack of non-invasive and long-term imaging modality for tracking the behavior of MSCs. Herein, copper-based nanozyme (Cu x O NPs) and gold nanoparticles (Au NPs) were encapsulated in oxidation-sensitive dextran (Oxi-Dex), a dextran derivative with reactive oxygen species (ROS)-responsiveness, forming a kind of novel nanocomposites (assigned as RSNPs) to act as ROS scavengers and computer tomography (CT) imaging tracers. After being internalized by MSCs, RSNPs enabled continuous CT imaging tracking of the transplanted MSCs for 21 days in IPF treatment, obtaining the location and distribution of the transplanted MSCs. Once MSCs were attacked by oxidative stress, the intracellular RSNPs could activate ROS clearance on demand by releasing Cu x O NPs, thereby enhancing the therapeutic efficacy against IPF by improving cell survival. Taken together, a novel multifunctional RSNP was fabricated to label MSCs for CT imaging tracking and clearing superfluous ROS, presenting a promising high-efficient IPF therapy.
研究领域:
纳米技术
·
干细胞疗法
·
医学成像
·
呼吸病学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Ziheng Bu,Jianxing Jing,Wei Liu,Zhen Fan,Junchao Huang,Zheng Zhou,Jianhai Hu,Jinxi An,Jiachang Hong,Jianing Yu,Daolin Tang,Min Sun,Jianzhong Du,Peng Wu
Denervated muscle atrophy, a common outcome of nerve injury, often results in irreversible fibrosis due to the limited effectiveness of current therapeutic interventions. While extracellular vesicles (EVs) offer promise for treating muscle atrophy, their therapeutic potential is hindered by challenges in delivery and bioactivity within the complex microenvironment of the injury site. To address this issue, an injectable hydrogel is developed that is responsive to both ultrasound and pH, with inherent anti-inflammatory and antioxidant properties, designed to improve the targeted delivery of stem cell-derived EVs. This hydrogel system allows for controlled release of EVs from human umbilical cord mesenchymal stem cells (HUC-MSCs), adapting to the specific conditions of the injury environment. In vivo studies using a rat model of nerve injury demonstrated that the EV-loaded hydrogel (EVs@UR-gel) significantly preserved muscle function. Six weeks post-nerve reconstruction, treated rats exhibited muscle strength, circumference, and wet weight reaching 89.53 ± 0.96%, 76.02 ± 7.49%, and 88.0 ± 2.65% of healthy controls, respectively, alongside an improvement in the sciatic nerve index (−0.11±0.09). This platform presents a novel therapeutic approach by maintaining EV bioactivity, enabling tunable release based on the disease state, and facilitating the restoration of muscle structure and function.
研究领域:
生物医学工程
·
组织工程
·
再生医学
·
肌肉骨骼疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
·
2024
·
IF 12.7
Fangyu Qiao,Yang Zou,Yonggang Lv
Peripheral nerves and blood vessels regulate the development process of bone tissue by delivering neural and vascular-related cytokines. However, challenge of preventing the loss of neural and vascular growth factors and ensuring their long-term availability for bone defects was often been overlooked. The current study designed a hybrid cell membrane with specific surface receptors for calcitonin receptor (CTR) and vascular endothelial growth factor receptor (VEGFR) through overexpressed the CTR receptor gene ( Calcr ) and the VEGFR 1 gene ( Flt-1 ). The bone repair matrix functionalized by the hybrid cell membrane (GCMs) had collecting property for neurogenic growth factor (NGF) and vascular endothelial growth factor (VEGF). Furthermore, GCMs enhanced neural and vascular differentiation in mesenchymal stem cells (MSCs) and stimulated osteogenic differentiation of MSCs through neural and vascular-related paracrine signals. GCMs also facilitated the angiogenesis and neurogenesis around bone defects, further promoted the repair of rat skull defects. This study suggests a promising approach for using cell membranes to harvest growth factors for innervation and vascularization in bone reconstruction.
研究领域:
组织工程
·
再生医学
·
骨生物学
·
干细胞研究
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Bailong Tao,Chuanchuan Lin,Ye He,Zhang Yuan,Maowen Chen,Kun Xu,Kai Li,Ai Guo,Kaiyong Cai,Lixue Chen
Bacterial infection and the resulting inflammation response not only affect the functions of osteogenic-relative cells but also lead to the failure of titanium (Ti)-based implantation. It is urgent to develop multifunctional (antimicrobial, anti-inflammation, and pre-osteogenesis) titanium implants to address this tissue. Herein, an osteogenic growth peptide (OGP) loaded zeolitic imidazolate frameworks-67 (ZIF-67) coating was fabricated on titanium dioxide nanotubes (TNTs) to prepare a [email protected] surface. The [email protected] coating was rapidly dissolved under an acidic environment with pH-sensitive property. Moreover, the [email protected] displayed a strong antibacterial activity against Escherichia coli ( E. coli ), Staphylococcus aureus ( S. aureus ), Streptococcus mutans ( S. mutans ), and methicillin-resistant Staphylococcus aureus ( MRSA ) owing to the hydrolysis of ZIF-67 nanoparticles and the formation of an alkaline microenvironment. The implants had good biocompatibility toward mesenchymal stromal cells (MSCs) and macrophages. Notably, the [email protected] could suppress the inflammatory response and simultaneously improve the cellular differentiation of MSCs under an inflammatory environment. In vivo study further revealed that [email protected] implants presented strong antimicrobial and anti-inflammatory properties at the early stage of implantation, thereby enhancing the osteointegration of bone-implant at the late stage. Thus, this multifunctional Ti implant combining osteoimmunomodulatory and antibacterial effects is a promising candidate for implant-associated infectious bone regeneration.
研究领域:
材料科学
·
生物医学工程
·
生物材料
·
骨科
·
免疫学
✓ 已验证
DOI
高影响因子
Advanced Fiber Materials
·
2022
·Vol. 5
·期 1
·312-326
·
IF 12.958
Huang Jinjian,Wu Jie,Wang Jiahang,Xu Mengjia,Jiao Jiao,Qiang Yuhao,Zhang Feng,Li Zongan
Impaired wound healing imposes great health risks to patients. Recently, mesenchymal stem cell (MSC) therapy has shown potential to improve the healing process, but approaches to employ MSCs in the treatment of wounds remain elusive. In this study, we reported a novel electrohydrodynamic (EHD) cyroprinting method to fabricate micropatterned fiber scaffolds with polycaprolactone (PCL) dissolved in glacial acetic acid (GAC). Cyroprinting ensured the formation of a porous structure of PCL fibers by preventing the evaporation of GAC, thus increasing the surface roughness parameter Ra from 11 to 130 nm. Similar to how rough rocks facilitate easy climbing, the rough surface of fibers was able to increase the adhesion of adipose-derived MSCs (AMSCs) by providing more binding sites; therefore, the cell paracrine action of secreting growth factors and chemokines was enhanced, promoting fibroblast migration and vascular endothelial cell tube formation. In rat models with one-centimeter wound defects, enhanced MSC therapy based on porous PCL fiber scaffolds improved wound healing by augmenting scarless collagen deposition and angiogenesis and reducing proinflammatory reactions. Altogether, this study offers a new and feasible strategy to modulate the surface topography of polymeric scaffolds to strengthen MSC therapy for wound healing. Graphic Abstract
研究领域:
生物医学工程
·
组织工程
·
干细胞治疗
·
伤口愈合
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2022
·
IF 18.027
Maowen Chen,Dong Wang,Menghuan Li,Ye He,Tingting He,Maohua Chen,Yan Hu,Zhong Luo,Kaiyong Cai
An elevated bone microenvironmental reactive oxygen species (ROS) level is a hallmark of osteoporosis that often leads to the dysfunction of bone-related mesenchymal stem cells (MSCs), which would induce MSC senescence and severely undermine their osteoblastic potential. Herein, we report the in situ construction of bone microenvironment-responsive biofunctional metal–organic framework (bio-MOF) coating on the titanium surface through the coordination between p-xylylenebisphosphonate (PXBP) and Ce/Sr ions by a hydrothermal method. Taking advantage of the anchored Ce and Sr ions, the AHT-Ce/SrMOF implants demonstrate on-demand superoxide dismutase and catalase-like catalytic activities to decompose ROS in MSCs and restore their mitochondrial functions. In vitro analysis showed that the AHT-Ce/SrMOF implants substantially activated the AMP-activated protein kinase (AMPK) signaling pathway in MSCs and reduced the ROS levels. Meanwhile, MSCs grown on AHT-Ce/SrMOF implants displayed significantly higher expressions of the mitochondrial fission marker (DRP1), mitochondrial fusion marker (MFN2 and OPA1), and mitophagy marker (PINK1 and LC3) than those of the AHT-CeMOF and AHT-SrMOF groups, which indicated that the bio-MOF could amend mitochondrial function in MSCs to reverse senescence. In vivo evaluations showed that the bio-MOF-coated Ti implants could restore MSC function in the implant site and promote new bone formation, leading to improved osteointegration in osteoporotic rat. This study may improve implant-mediated fracture healing in the clinics.
研究领域:
生物材料
·
组织工程
·
再生医学
·
生物医学工程
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 9
·2459-2471
·
IF 6.183
Tian Ding,Jianhua Li,Xingshuang Zhang,Lingqian Du,Yang Li,Dengwang Li,Biao Kong,Shaohua Ge
The regeneration of periodontal tissue defects remains a clinical challenge due to its complex tissue structure (e.g. periodontal ligament, alveolar bone and cementum) and poor self-healing ability. In situ tissue engineering has emerged as a promising approach that combines frameworks with growth factors that are specifically chosen for the recruitment of endogenous stem cells to the site of injury and to evoke the innate regenerative potential of the body. Herein, a core/shell fibrous super-assembled framework (SAF)-based sequential growth factor delivery system is developed, in which basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) are designed to release in a sequential manner to facilitate in situ regeneration of the cementum–ligament–bone complex. The in situ tissue engineering framework (iTE-framework) shows ameliorated physicochemical properties and improved hydrophilicity, with an initial burst release of bFGF in the first few days, followed by a slow and constant release of BMP-2 up to 4 weeks. The iTE-framework shows excellent biocompatibility, significantly promoting the proliferation, migration and osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) in vitro. After implantation in rat periodontal defects, the iTE-framework effectively triggers the recruitment of mesenchymal stem cells (MSCs) to the defect site, significantly promotes the formation of new bones, and facilitates the regeneration of the periodontal ligament and cementum tissue in vivo. Therefore, this sequential delivery system provides a promising therapeutic strategy for cementum–ligament–bone complex regeneration.
研究领域:
组织工程
·
牙科材料
·
再生医学
·
干细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Min Wu,Yitao Zhao,Meihan Tao,Meimei Fu,Yue Wang,Qi Liu,Zhihui Lu,Jinshan Guo
The latest advancements in cellular bioenergetics have revealed the potential of transferring chemical energy to biological energy for therapeutic applications. Despite efforts, a three-dimensional (3D) scaffold that can induce long-term bioenergetic effects and facilitate tissue regeneration remains a big challenge. Herein, the cellular energetic metabolism promotion ability of l-malate, an important intermediate of the tricarboxylic acid (TCA) cycle, was proved, and a series of bioenergetic porous scaffolds were fabricated by synthesizing poly(diol l-malate) (PDoM) prepolymers via a facial one-pot polycondensation of l-malic acid and aliphatic diols, followed by scaffold fabrication and thermal-cross-linking. The degradation products of the developed PDoM scaffolds can regulate the metabolic microenvironment by entering mitochondria and participating in the TCA cycle to elevate intracellular adenosine triphosphate (ATP) levels, thus promoting the cellular biosynthesis, including the production of collagen type I (Col1a1), fibronectin 1 (Fn1), and actin alpha 2 (Acta2/α-Sma). The porous PDoM scaffold was demonstrated to support the growth of the cocultured mesenchymal stem cells (MSCs) and promote their secretion of bioactive molecules [such as vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and basic fibroblast growth factor (bFGF)], and this stem cells-laden scaffold architecture was proved to accelerate wound healing in a critical full-thickness skin defect model on rats.
研究领域:
生物医学工程
·
组织工程
·
细胞生物能学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）