Polymers
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2022
·Vol. 15
·期 1
·108
·
IF 4.967
Bin Chu,Xiaoli Li,Shiqiang Fan,Jinmei He,Xiaohong Ge,Hui Li,Changsheng Chen,Zhen Wang,Song Wang,Boning Li
Biodegradable materials are a next-generation invention for the treatment of congenital heart diseases. However, the corresponding technology used to develop ideal biomaterials still presents challenges. We previously reported the first biodegradable atrial septal defect (ASD) occluder made of poly-lactic acid (PLLA). Unfortunately, the PLLA occluder had a limited endothelialization effect. In this study, the surface of the occluder membrane was coated with sericin/CD34 antibodies to promote the growth of endothelial cells and the regeneration of defective tissue and enhance the repair of the atrial septal defect. The physicochemical properties of the coat on the surface of the fiber membrane were characterized. The sericin coat successfully covered the fiber surface of the membrane, and the thickness of the membrane increased with the sericin concentration. The swelling rate reached 230%. The microscopic observation of fluorescently labeled CD34 antibodies showed that the antibodies successfully attached to the fiber membrane; the fluorescence intensity of PLLA-SH5 was particularly high. The in vitro experiment showed that the PLLA-SH-CD34 fiber membrane was biocompatible and promoted the adhesion and proliferation of endothelial cells. According to our findings, the PLLA-SH-CD34 membrane provides a theoretical and technical basis for the research and development of novel biodegradable occluders.Keywords:biodegradable;CD34 antibody;endothelialization;fiber membrane
研究领域:
生物医学工程
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组织工程
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心血管疾病
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DOI
PubMed
高影响因子
Brazilian Journal of Cardiovascular Surgery
·
2015
·Vol. 30
·期 2
·159-163
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IF 0.55
Song Chun-Li,Li Qian,Yu Yun-Peng,Wang Guan,Wang Jin-Peng,Lu Yang,Zhang Ji-Chang,Diao Hong-Ying,Liu Jian-Gen,Liu Yi-Hang,Liu Jia,Li Ying,Cai Dan,Liu Bin
Introduction: Intravascular coronary stenting has been used in the treatment of coronary artery disease (CAD), with a major limitation of in-stent restenosis (ISR). The 316 stainless steel has been widely used for coronary stents. In this study, we developed a novel coating method to reduce ISR by simultaneously coating vascular endothelial growth factor (VEGF) and anti-CD34 antibody on 316L stainless steel. Methods: Round 316L stainless steel sheets in the D-H group were polymerized with compounds generated from condensation reaction of dopamine and heparin using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS). Sixteen sheets from the D-H group were further immersed into 1ug/ml VEGF165 and 3mg/ml heparin sodium one after another for 10 times, and named as the D-(H-V)10 group. Eight sheets from the D-(H-V)10 group were coated with anti-CD34 antibody and termed as the D-(H-V)10-A group. Immunofluorescence assay and ELISA were used to evaluate whether the 316L stainless steel disks were successfully coated with VEGF and anti-CD34 antibody. Results: The results of immunofluorescence assay and ELISA showed that VEGF could be detected in the D-(H-V)10 and D-(H-V)10-A group, suggesting the steel sheets were successfully covered with VEGF. Anti-CD34 antibody could only be observed in the D-(H-V)10-A group, which was the only group coated with CD34 antibody. Both results suggested that the 316L stainless steel sheets were successfully coated with VEGF and anti-CD34 antibody. Conclusion: Our study developed a method to simultaneously coat VEGF and anti-CD34 antibody to stainless metal steel. This research serves as a fundamental role for a novel coating strategy.
研究领域:
心血管工程
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生物材料
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医疗器械
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2021
·
IF 4.749
Lidan Chen,Dezhi Zhou,Xinda Li,Bin Yang,Tao Xu
The three-dimensional (3D) marrow microenvironment plays an essential role in regulating human cord blood-derived CD34+ cells (hCB-CD34+) migration, proliferation, and differentiation. Extensive in vitro and in vivo studies have aimed to recapitulate the main components of the bone marrow (BM) niche. Nonetheless, the models are limited by a lack of heterogeneity and compound structure. Here, we fabricated coaxial extruded core–shell tubular scaffolds and extrusion-based bioprinted cell-laden mesh scaffolds to mimic the functional niche in vitro. A multicellular mesh scaffold and two different core–shell tubular scaffolds were developed with human bone marrow-derived mesenchymal stromal cells (BMSCs) in comparison with a conventional 2D coculture system. A clear cell–cell connection was established in all three bioprinted constructs. Cell distribution and morphology were observed in different systems with scanning electron microscopy (SEM). Collected hCB-CD34+ cells were characterized by various stem cell-specific and lineage-specific phenotypic parameters. The results showed that compared with hCB-CD34+ cells cocultured with BMSCs in Petri dishes, the self-renewal potential of hCB-CD34+ cells was stronger in the tubular scaffolds after 14 days. Besides, cells in these core–shell constructs tended to obtain stronger differentiation potential of lymphoid and megakaryocytes, while cells encapsulated in mesh scaffolds obtained stronger differentiation tendency into erythroid cells. Consequently, 3D bioprinting technology could partially simulate the niche of human hematopoietic stem cells. The three models have their potential in stemness maintenance and multilineage differentiation. This study can provide initial effective guidance in the directed differentiation research and related screening of drug models for hematological diseases.
研究领域:
组织工程
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血液学
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干细胞生物学
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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
ACS Omega
·
2024
·
IF 3.7
Yao Zuo,Hongwen Li,Xiaochao Wang,Yejin Liang,Caihong Huang,Guanye Nai,Jingrong Ruan,Wenzheng Dong,Xiang Lu
Acute myeloid leukemia (AML) is a relatively common malignant hematological disease whose development is mostly associated with abnormal activation of the JAK/STAT3 signaling pathway. Our previous study revealed that SAR317461, a novel JAK2/STAT3 inhibitor, can effectively inhibit the activation of the JAK2/STAT3 signaling pathway and has significant damaging and pro-apoptotic effects on AML cell lines. This project aims to build upon our prior research to enhance the application of SAR317461 in AML. The surface modification of liposomes with the CD34 antibody, along with the inclusion of the SAR317461 and cytarabine (a common AML chemotherapeutic agent), is observed. Due to the high expression of CD34 on the surface of AML cells, the nanoliposome could target AML cells specifically, further achieving an effective treatment for AML through the synergistic effect of JAK2/STAT3 inhibitors and chemotherapeutic agents. The implementation of this project will provide more theoretical support and ideas for the clinical application of JAK/STAT3 inhibitors in malignant tumors and for overcoming chemotherapy resistance.
研究领域:
肿瘤学
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血液学
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药学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2026
·
IF 6.8
Teng Wang,Weilin Liu,Chunyi Lyu,Yunxiao Luo,Xinyu Tang,Chen Han,Ruirong Xu
Ethnopharmacological relevance Realgar is an arsenic-containing mineral medicine and a key component of Realgar-Indigo naturalis formula, an oral traditional Chinese medicine preparation clinically used in China for acute promyelocytic leukemia (APL), a biologically distinct subtype of acute myeloid leukemia (AML). Realgar Transforming Solution (RTS) is a microbially processed realgar preparation. Its activity in AML stem cell-like contexts outside APL remains insufficiently defined, particularly in cell-line-derived CD34 + CD38 − LSC-like models. Aim of the study: To evaluate whether RTS suppresses stemness-associated phenotypic features in KG-1a-derived CD34 + CD38 − LSC-like cells and to explore its association with endoplasmic reticulum stress (ERS), mitochondrial injury, and mitophagy-related alterations. Materials and methods CD34 + CD38 − LSC-like cells were enriched from KG-1a cells and used as a cell-line-derived in vitro model. Cell viability, apoptosis, cell cycle, CD34 + CD38 − fraction, colony formation, and TIM3/ HAVCR2 expression were assessed after RTS treatment. RNA sequencing, Ca 2+ measurement, ROS detection, mitochondrial membrane potential assay, MDC staining, western blotting, RT-qPCR, immunofluorescence, and transmission electron microscopy were performed. 4-phenylbutyric acid and Mdivi-1 were used as pharmacological rescue agents. Results RTS reduced the CD34 + CD38 − fraction, colony formation, and TIM3/ HAVCR2 expression, while inducing apoptosis in KG-1a-derived LSC-like cells. Transcriptomics implicated ER protein processing, unfolded protein response, apoptosis, autophagy, and mitophagy-related pathways. RTS increased Ca 2+ levels, ROS accumulation, mitochondrial depolarization, PERK-eIF2α-ATF4-CHOP signaling, and PINK1/Parkin-associated mitophagy-like marker changes. 4-phenylbutyric acid and Mdivi-1 partially rescued RTS-impaired LSC-like phenotypic features, supporting pathway involvement. Conclusions RTS suppressed stemness-associated phenotypic features in a KG-1a-derived CD34 + CD38 − LSC-like model. These effects were associated with ERS, mitochondrial injury, and PINK1/Parkin-related mitophagy-like alterations.
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PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Jing Hong,Zhanchi Zhu,Leisha Cui,Zhaojun Wang,Ying Hao,Xiaopeng Tian,Guosheng Cheng
Hematopoietic stem cell (HSC) expansion offers a key strategy to address the source limitation and donor shortages of HSCs for the treatment of various blood disorders. Specific remodeling of the complex bone marrow microenvironment that contributes to efficient in vitro expansion of HSCs remains challenging. Here, inspired by the regions with different stiffness levels in the bone marrow niche, a three dimensional (3D) bone marrow-mimicking composite scaffold created based on gelatin–hyaluronic acid (Gel–HA) hydrogels and graphene foams (GFs) was engineered to support the in vitro expansion of HSCs. The composite scaffold was prepared by forming a photo-cross-linked Gel–HA hydrogel surrounding the GF. The “soft” Gel–HA hydrogel and “stiff” GF replicate the structure and stiffness of the vascular niche and endosteal niche in the bone marrow, respectively. Furthermore, HSCs cultured in the Gel–HA/GF scaffold proliferated well and retained the CD34+CD38− immunophenotype and pluripotency, suggesting that the Gel–HA/GF composite scaffold supported the in vitro expansion of HSCs, maintaining the primitive phenotype and the ability to differentiate into functional blood cells. Thus, the hydrogel/graphene composite scaffold offers a means of facilitating HSC expansion through structurally and mechanically mimicking bone marrow niches, demonstrating great promise for HSC transplantation.
研究领域:
生物材料
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组织工程
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干细胞生物学
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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
Pharmaceutics
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2024
·Vol. 16
·期 7
·870
·
IF 4.9
Zikang Xing,Xuewen Li,Zhen Ning Tony He,Xin Fang,Heng Liang,Chunxiang Kuang,Aiying Li,Qing Yang
Glioma is characterized by strong immunosuppression and excessive angiogenesis. Based on existing reports, it can be speculated that the resistance to anti-angiogenic drug vascular endothelial growth factor A (VEGFA) antibody correlates to the induction of novel immune checkpoint indoleamine 2,3-dioxygenase 1 (IDO1), while IDO1 has also been suggested to be related to tumor angiogenesis. Herein, we aim to clarify the potential role of IDO1 in glioma angiogenesis and the mechanism behind it. Bioinformatic analyses showed that the expressions of IDO1 and angiogenesis markers VEGFA and CD34 were positively correlated and increased with pathological grade in glioma. IDO1-overexpression-derived-tryptophan depletion activated the general control nonderepressible 2 (GCN2) pathway and upregulated VEGFA in glioma cells. The tube formation ability of angiogenesis model cells could be inhibited by IDO1 inhibitors and influenced by the activity and expression of IDO1 in condition medium. A significant increase in serum VEGFA concentration and tumor CD34 expression was observed in IDO1-overexpressing GL261 subcutaneous glioma-bearing mice. IDO1 inhibitor RY103 showed positive anti-tumor efficacy, including the anti-angiogenesis effect and upregulation of natural killer cells in GL261 glioma-bearing mice. As expected, the combination of RY103 and anti-angiogenesis agent sunitinib was proved to be a better therapeutic strategy than either monotherapy.
研究领域:
肿瘤学
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免疫学
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分子生物学
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神经科学
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DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
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2021
·
IF 7.328
Anqi Sun,Xiuhong Huang,Yanpeng Jiao,Xiangyu Wang,Jun Wen
Recently, just taking endothelialization of stent as an interventional treatment of aneurysms is unsatisfactory. This treatment also has impacts the occlusion rate of the aneurysm. In accordance with that, the authors aims to construct a novel biological factor-coated stent with dual biological effects of anticoagulation and endothelialization for the improvement of the occlusion rate of aneurysms and reduction of the risk for treatment of aneurysm with intravascular interventional therapy. The Ni-Ti alloy sheets loaded with VEGF and anti-CD34 antibody were put into use for stimulating the construction of the biological factor-coated stents, for the Ni-Ti alloy sheets could help improve the proliferation of endothelial cell (EC), recognize effectively and adhere to endothelial progenitor cell (EPC). Blood compatibility characterization methods (water contact angle, platelet activation test, clotting time evaluation and protein adsorption test) were applied for study the influence of the interaction between the Ni-Ti alloy sheets and blood. Cell experiments (HUVEC proliferation experiment, migration experiment and EPC capture experiment) were resorted to investigate the ability of the sheets to promote the proliferation of HUVEC and to capture EPCs. With the mature of the construction technology, the Enterprise stent with the biological factors were optimized accordingly, the biological function of that were verified by cell experiments. Studies showed that Ni-Ti alloy sheets and enterprise stents can successfully load with VEGF and anti-CD34 antibody. The below achievements can be realized including a better blood compatibility and effects of the constructed sheets and enterprise stents on promoting HUVEC proliferation and adhesion of EPC. It was meaningful of conversion to clinical application to improve the cure rate of the aneurysm and the safety of the intravascular treatment.
研究领域:
生物医学工程
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心血管医学
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材料科学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
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
INTERNATIONAL IMMUNOPHARMACOLOGY
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2026
·
IF 5.6
Yu Dun,Jinxi Xie,Jian Zhou,Hanbing Hu,Fuli Liu,Yiru Shao,Jie Shen
CD34/CD45-DSCs alleviate phosgene-induced acute lung injury (P-ALI) in rats. • CD34 + CD45 + cells reside in bone marrow, peripheral blood, and BALF with dynamic changes post-injury. • CD34/CD45-DSCs exhibit MSC-like properties with osteogenic, adipogenic, and chondrogenic potential in vitro. • CD34/CD45-DSCs showed prolonged lung retention perivascular engraftment, and PVSC-like phenotype acquisition without exacerbating fibrosis. • CD34/CD45-DSCs restore pulmonary vascular barrier via VEGF-PI3K/AKT/eNOS signaling pathway. Phosgene inhalation causes acute lung injury (ALI) with high mortality and no effective antidote, and stem cell therapy is limited by poor cell survival and low engraftment efficiency. Here, we identified a rare endogenous CD34 + CD45 + cell fraction that reside in bone marrow, peripheral blood, and bronchoalveolar lavage fluid (∼1% baseline), exhibits a “decrease-then-recovery” dynamic after phosgene injury, and displays MSC-like properties with trilineage (osteogenic, adipogenic, and chondrogenic) potential in vitro. Intravenous administration of expanded CD34 + CD45 + -derived stromal cells (CD34/CD45-DSCs) significantly alleviated pulmonary vascular leakage and inflammatory in a rat model of phosgene-induced ALI (P-ALI). In vivo bioluminescence imaging further revealed that CD34/CD45-DSCs exhibited prolonged pulmonary retention compared with BMSCs (11.3 days vs. 48 h), proliferated, engrafted around the pulmonary vasculature, and acquired a perivascular stromal cell (PVSC)-like phenotype expressing late-stage mesenchymal progenitor, pericyte, and fibroblast markers. In a bleomycin-induced pulmonary fibrosis model, CD34/CD45-DSCs did not exacerbate fibrotic changes at day 28. Mechanistically, VEGF knockdown or neutralization abolished the barrier-protective effect, which was rescued by an AKT agonist and blocked by an inhibitor. Moreover, CD34/CD45-DSCs upregulated tight junction proteins ZO-1 and Occludin in injured endothelial cells via VEGF-PI3K/AKT/eNOS signaling. Collectively, our study defines the origin, spatiotemporal dynamics, perivasucular engraftment, PVSC-like fate acquisition, and VEGF-PI3K/AKT/eNOS-dependent mechanism of CD34/CD45-DSCs, supporting their potential as a relatively safe, long-engrafting, and mechanistically transparent cell-based strategy for ALI.
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DOI
PubMed
高影响因子
Acta Biomaterialia
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2021
·
IF 8.947
Shunbo Wei,Yanhua Xu,Zhiwei Wang,Mingxing Li,Peng Sun,Boao Xie,Ying Xing,Hualong Bai,Quancheng Kan,Jiang'an Li,Alan Dardik
Introduction Incomplete hemostasis after vascular cannulation can cause a hematoma or pseudoaneurysm. We hypothesized that a hydrogel-coated needle would effectively and rapidly stop bleeding after vascular cannulation. Methods : A hydrogel composed of sodium alginate , hyaluronic acid , and calcium carbonate was coated onto the surface of suture needles. Needles were observed using scanning electronic microscopy (SEM) and immunofluorescence. Cannulation was performed in both mouse and rat models; the liver, kidney, jugular vein, inferior vena cava and aorta were punctured using uncoated and hydrogel-coated needles. Needles coated with a hydrogel with and without CD34 antibody were used to puncture the rat jugular vein and aorta. Tissues were examined by histology and immunofluorescence. Results : The hydrogel was successfully coated onto the surface of 22G and 30G needles and confirmed by SEM. Hydrogel-coated needles rapidly stopped bleeding after cannulation of the liver, kidney, jugular vein, inferior vena cava and aorta. Hydrogel-coated needles that contained CD34 antibody attracted vascular progenitor cells near the puncture site; there were fewer M1-type macrophages and more M2-type macrophages. Conclusion : Hydrogel-coated needles can effectively and rapidly stop puncture-site bleeding. The hydrogel that contains CD34 antibody attracted vascular progenitor cells, potentially promoting healing of the site after cannulation. Statement of significance Incomplete hemostasis after vascular cannulation can cause a hematoma or pseudoaneurysm and remains a significant clinical problem. We developed a hydrogel composed of sodium alginate, hyaluronic acid, and calcium carbonate; hydrogel-coated needles effectively and rapidly stopped bleeding after vascular cannulation. Interestingly, the hydrogel can also serve as a carrier for drugs that are delivered to the puncture site during the short time of cannulation that could additionally promote puncture site healing. Hydrogel-coated needles may be a new method for rapid hemostasis with application to patients especially at risk for bleeding.
研究领域:
止血
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血管外科
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生物医学工程
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组织工程
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2024
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IF 18
Guoyang Zhang,Yuhao Kang,Jizhao Dong,Dingyi Shi,Yu Xiang,Haihan Gao,Zhiqi Lin,Xiaojuan Wei,Ren Ding,Beibei Fan,Hongmei Zhang,Tonghe Zhu,Liren Wang,Xiaoyu Yan
Osteoporosis is majorly caused by an imbalance between osteoclastic and osteogenic niches. Despite the development of nationally recognized first-line anti-osteoporosis drugs, including alendronate (AL), their low bioavailability, poor uptake rate, and dose-related side effects present significant challenges in treatment. This calls for an urgent need for more effective bone-affinity drug delivery systems. In this study, we produced hybrid structures with bioactive components and stable fluffy topological morphology by cross-linking calcium and phosphorus precursors based on mesoporous silica to fabricate nanoadjuvants for AL delivery. The subsequent grafting of -PEG-DAsp 8 ensured superior biocompatibility and bone targeting capacity. RNA sequencing revealed that these fluffy nanoadjuvants effectively activated adhesion pathways through CARD11 and CD34 molecular mechanisms, hence promoting cellular uptake and intracellular delivery of AL. Experiments showed that small-dose AL nanoadjuvants effectively suppress osteoclast formation and potentially promote osteogenesis. In vivo results restored the balance between osteogenic and osteoclastic niches against osteoporosis as well as the consequent significant recovery of bone mass. Therefore, this study constructed a drug nanoadjuvant with peculiar topological structures and high bone targeting capacities, efficient intracellular drug delivery as well as bone bioactivity. This provides a novel perspective on drug delivery for osteoporosis and treatment strategies for other bone diseases.
研究领域:
药理学
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纳米技术
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骨骼生物学
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药物递送系统
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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）