INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED
·
2023
·
IF 2.5
Fangyuan Lai,Shijie Dai,Ye Zhao,Yi Sun
Adipose-derived stem cells (ADSCs) have been widely proven to facilitate wound healing. Our study aimed to estimate the influence of combined ADSCs and platelet-derived growth factor-BB (PDGF-BB) on wound healing. We utilized 4 healthy SD rats to isolate ADSCs. Platelet-rich plasma (PRP) was acquired utilizing a two-step centrifugation technology. The role of PRP, PDGF-BB, and PDGF-BB combined with a PI3k inhibitor LY294002 on the viability, migration, and PTEN/AKT pathway in ADSCs were examined utilizing CCK-8, Transwell, and western blot assays. Then, we constructed an open trauma model in SD rats. Effects of ADSCs treated with PDGF-BB on pathological changes, CD31, and PTEN/AKT pathway of wound closure were assessed by hematoxylin & eosin (H&E) staining, Masson staining, immunohistochemical, and western blot assays, respectively. PRP and PDGF-BB intensified the viability and migration of ADSCs by modulating the PTEN/AKT pathway. Interestingly, LY294002 reversed the role of PDGF-BB on ADSCs. In vivo experiments, combined intervention with ADSCs plus PDGF-BB/PRP facilitated wound closure and ameliorated histological injury. Moreover, combined intervention with ADSCs and PDGF-BB attenuated the PTEN level and elevated the CD31 level as well as the ratio of p-AKT/AKT in the skin tissues. A combination of ADSCs and PDGF-BB facilitated wound healing might associate with the regulation of the PTEN/AKT pathway.
研究领域:
再生医学
·
伤口愈合
·
细胞生物学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
BONE
·
2022
·
IF 4.626
Huijuan Cao,Keda Shi,Jing Long,Yanzhi Liu,Lingli Li,Tianluo Ye,Cuishan Huang,Yuxiao Lai,Xueling Bai,Ling Qin,Xinluan Wang
Destructive repair characterized by inadequate angiogenesis and osteogenesis is the main pathological progression in steroid-associated osteonecrosis of the femoral head (SONFH). Platelet-derived growth factor-BB (PDGF-BB) is an “angiogenesis and osteogenesis coupling” factor that has been used for the treatment of bone defects in clinic. This study was designed to analyze the ability of PDGF-BB for preventing destructive repair and promoting reparative osteogenesis in SONFH. Steroid-associated osteonecrosis (SAON) was induced and triggered destructive repair of the femoral head by repeated lipopolysaccharide (LPS) and methylprednisolone (MPS) injections in rabbits. At 2, 4, and 6 weeks after induction, recombinant human PDGF-BB, neutralizing PDGF-BB antibody, or saline was intramedullary injected into the proximal femora . At week 6 after SAON induction, the proximal femora were dissected for bone architecture and histological analysis. C3H10T1/2 cells and HUVECs were used for further mechanistic investigation. After PDGF-BB treatment, type H vessels and leptin receptor-positive (LepR+) mesenchymal stem cells (MSCs) increased in the affected femoral head, and more osteoblastic osteogenesis along the bone surfaces but scattered adipocytes in bone marrow tissue than that in the SAON group. PDGF-BB treatment prevented destructive repair progression and led to 50–70 % of osteonecrotic femoral heads undergoing reparative osteogenesis. In particular, we found that PDGF-BB could mediate MSC self-renewal and maintain their osteogenic potency by activating PDGFR/Akt/GSK3β/CERB signaling in the presence of steroids. Moreover, PDGF-BB also stabled the newly formed vascular tubes by recruiting MSCs for improving intraosseous vascular integration. PDGF-BB may be a candidate for the promotion of reparative osteogenesis in SONFH.
研究领域:
骨科
·
再生医学
·
骨生物学
·
干细胞研究
✓ 已验证
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2023
·
IF 3.7
Hai-Tao Yang,Guan Wang,Peng-Cheng Zhu,Zhao-Yang Xiao
Pulmonary vascular remodeling caused by the excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) is the hallmark feature of pulmonary arterial hypertension (PAH). Eukaryotic initiation factor 3 subunit A (EIF3A) exhibited proliferative activity in multiple cell types. The present study investigated the role of EIF3A in the progression of PAH. A monocrotaline (MCT)-induced PAH rat model was constructed, and adeno-associated virus type 1 (AAV1) carrying EIF3A shRNA was intratracheally delivered to PAH rats to block EIF3A expression. PASMCs were isolated from rats and treated with PDGF-BB to simulate PASMC proliferation , and shRNA for EIF3 was conducted to investigate the mechanism behind the role of EIF3A in PASMC function in vitro . EIF3A expression was upregulated in pulmonary arteries, and EIF3A inhibition effectively improved pulmonary hypertension and right ventricular hypertrophy and suppressed MCT-induced vascular remodeling in vivo . In addition, we found that genetic knockdown of EIF3A reduced PDGF-triggered proliferation and arrested cell cycle, accompanied by downregulated proliferation-related protein expression in PASMCs. Mechanistically, the histone deacetylase 1 (HDAC1)-mediated PTEN/PI3K/AKT pathway was recognized as a primary mechanism in PAH progression. Silencing EIF3A decreased HDAC1 expression, and further inhibited the excessive proliferation of PASMCs by increasing the phosphatase and tension homolog (PTEN) expression and suppressing the AKT phosphorylation. Notably, HDAC1 expression reversed the effect of silencing EIF3A on PAH and PTEN/PI3K/AKT pathway. Collectively, silencing EIF3A improved PAH by decreasing PASMC proliferation through the HDAC1-mediated PTEN/PI3K/AKT pathway. These findings suggest that targeting EIF3A may represent a potential approach for the treatment of PAH.
研究领域:
心血管疾病
·
分子生物学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Advances
·
2022
·
IF 9.918
Qingdong Li,Jianmin Xiao,Caiyun Zhang,Peng Wang,Wenling Li,Yinfeng Wang,Lang Ran,Xia Qin,Miao Yan,Junchao Qian,Zhengyan Wu,Geng Tian,Pengfei Wei,Guilong Zhang
The development of highly efficient magnetic resonance imaging (MRI) contrast agent contributes to the early and accurate diagnosis of cancer. Herein, we developed a novel iron oxide and gadolinium oxide (IO/GdO) nanocomposite as T 1 -T 2 dual modal MRI contrast agent through hydrothermal synthesis method. Subsequently, tumor-targeting ligand (PDGFB-PEG) was further conjugated to the surface of IO/GdO nanocomposite (PDGFB-pIO/GdO) to fabricate tumor-targeting MRI probe for accurate diagnosis of orthotopic prostatic cancer. IO/GdO nanocomposite exhibited obvious mesoporous structure, which would promote the contact between water molecules and Gd or Fe centers and enhance the T 1 relaxation rate (r 1 ) and T 2 relaxation rate (r 2 ) of IO/GdO composite. In addition, the r 1 and r 2 values of IO/GdO composite were up to be 11.6 mM −1 s −1 and 102.7 mM −1 s −1 , respectively, and the r 2 /r 1 ratio of IO/GdO nanocomposite was calculated to be 8.85, demonstrating a great potential as dual-mode MRI contrast agent. Further study indicated that PDGFB-pIO/GdO exhibited an excellent biocompatibility. Besides, PDGFB-pIO/GdO presented a higher accumulation in tumor than untargeted pIO/GdO, confirming its excellent in vivo tumor-targeting ability. Lastly, in orthotopic prostatic cancer model, the systemic delivery of PDGFB-pIO/GdO significantly enhanced T 1 - and T 2 -weighted signal of orthotopic prostatic cancer, achieving high quality of MR images and realizing accurate diagnosis of orthotopic prostatic cancer. Collectively, we proposed a rational designed nanoplatform, PDGF-B conjugating mesoporous IO/GdO nanocomposites, suggesting potential for diagnostic identification of prostate cancer via T 1 -T 2 dual-modal MRI contrast enhancement.
研究领域:
纳米技术
·
医学成像
·
癌症诊断
·
材料科学
·
生物医学工程
✓ 已验证
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2021
·Vol. 31
·期 48
·2105084
·
IF 18.808
Yiting Lei,Yuping Wang,Jieliang Shen,Zhengwei Cai,Yongsheng Zeng,Piao Zhao,Junyi Liao,Chengjie Lian,Ning Hu,Xiaoji Luo,Wenguo Cui,Wei Huang
The differentiation potentials and viability of stem cells are often impaired during cell isolation and delivery. Inspired by the phenomenon where islands can recruit seabirds for nesting, “cell island” microgels (MGs), that is, growth factor-loaded methacrylated hyaluronic acid and heparin blend MGs, which can recruit endogenous stem cells and promote chondrogenic differentiation, are constructed using microfluidic technology and photopolymerization processes, followed by non-covalently binding platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-beta3 (TGF-β3). The loading efficiency of PDGF-BB and TGF-β3 are 96% and 91%, respectively. In vitro and in vivo experiments find that the “cell island” MGs can enhance the migratory capacity of cells and recruit them from their niche via releasing PDGF-BB. Meanwhile, by using hyaluronic acid, the “cell island” MGs provide a suitable microenvironment for cell attachment and spreading. Furthermore, the “cell island” MGs induce chondrogenic differentiation of the recruited cells via releasing TGF-β3 and present a promising therapeutic effect for osteoarthritis. In sum, this developed “cell island” MG might serve as a temporary “nest site” to allow the migration, adhesion, and differentiation of endogenous stem cells, which can be a promising candidate rather than the conventional cell-seeded scaffolds for promoting tissue regeneration.
研究领域:
生物医学工程
·
组织工程
·
再生医学
✓ 已验证
DOI
高影响因子
Experimental and Therapeutic Medicine
·
2024
·Vol. 28
·期 3
·1-11
·
IF 2.4
Wenxian Tu,Meina Feng,Qin Zhou,Yunfeng Wang,Mingye Wan,Danqun Gong,Jin Li,Yuanmin Du
Evidence has shown that microRNAs (miRNAs/
miRs) play key roles in biological functions of vascular smooth muscle cells (VSMCs). However, the role of miR‑374a in VSMCs remains to be elucidated. The present study aimed to explore the influence of miR‑374a on VSMCs and its molecular mechanism. The expression level of miR‑374a was measured by reverse transcription‑quantitative (RT‑q) PCR. MTT and Transwell assay were employed to assess the role of miR‑374a in proliferation and migration of VSMCs. To order to determine miR‑374a targets, a dual‑luciferase reporter assay was conducted, which was further verified by rescue experiments. Chromatin Immunoprecipitation Assay and JASPAR databases were applied to explore the regulatory association between GATA binding protein 2 (GATA2) and miR‑374a. Western blotting or RT‑qPCR were employed to detect the protein expression levels of GATA2 or RAR‑related orphan receptor A (RORA). The present study found that miR‑374a was elevated in VSMCs following treatment with platelet‑derived growth factor‑BB (PDGF‑BB) compared with that in control group. In addition, the results demonstrated that a higher expression of a miR‑374a could promote proliferation and migration of VSMCs while miR‑374a inhibitor suppressed the PDGF‑BB‑induced proliferation and migration of VSMCs in vitro. Furthermore, circTADA2A bound to miR‑374a and then upregulated RORA expression, which resulted in inhibition in VSMCs proliferation and migration. On the other hand, the result indicated that GATA2 overexpression could augment the proliferation, migration of PDGF‑bb‑induced VSMCs, which could be rescued by miR‑374a inhibitor. The findings suggested that the GATA2/circTADA2A‑miR‑374a axis promoted the proliferation and migration of VSMCs by targeting RORA, which were closely related to atherosclerosis (AS). Thus the results might offer a new therapeutic target for AS.
研究领域:
分子生物学
·
心血管疾病
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2024
·
IF 4.6
Jingyu Li,Zhuoting Lu,Liwang Xu,Jing Wang,Shaojie Qian,Qinglian Hu,Yunfen Ge
Hindlimb ischemia is a common disease worldwide featured by the sudden decrease in limb perfusion, which usually causes a potential threat to limb viability and even amputation or death. Revascularization has been defined as the gold-standard therapy for hindlimb ischemia. Considering that vascular injury recovery requires cellular adaptation to the hypoxia, hypoxia-inducible factor 1 α (HIF-1α) is a potential gene for tissue restoration and angiogenesis. In this manuscript, effective gene delivery vector PEI-β-CD (PC) was reported for the first application in the hindlimb ischemia treatment to deliver HIF-1α plasmid in vitro and in vivo. Our in vitro finding demonstrated that PC/HIF-1α-pDNA could be successfully entered into the cells and mediated efficient gene transfection with good biocompatibility. More importantly, under hypoxic conditions, PC/HIF-1α-pDNA could up-regulate the HUEVC cell viability. In addition, the mRNA levels of VEGF, Ang-1, and PDGF were upregulated, and transcriptome results also demonstrated that the cell-related function of response to hypoxia was enhanced. The therapeutic effect of PC/HIF-1α-pDNA was further estimated in a murine acute hindlimb ischemia model, which demonstrated that intramuscular injection of PC/HIF-1α-pDNA resulted in significantly increased blood perfusion and alleviation in tissue damage, such as tissue fibrosis and inflammation. The results provide a rationale that HIF-1α-mediated gene therapy might be a practical strategy for the treatment of limb ischemia.
研究领域:
生物医学工程
·
分子生物学
·
基因治疗
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 8
·1832
·
IF 4.2
Pin Luo,Wei Liu,Zhangyao Ye,Yuyu Zhang,Zekun Zhang,Jing Yi,Rong Zeng,Shenyu Yang,Mei Tu
Diabetic wound healing is a significant clinical challenge because abnormal immune cells in the wound cause chronic inflammation and impair tissue regeneration. Therefore, regulating the behavior and function of macrophages may be conducive to improving treatment outcomes in diabetic wounds. Herein, sulfated chitosan (26SCS)-containing composite sponges (26SCS-SilMA/Col-330) with well-arranged layers and high porosity were constructed based on collagen and silk fibroin, aiming to induce an appropriate inflammatory response and promote angiogenesis. The results indicated that the ordered topological structure of composite sponges could trigger the pro-inflammatory response of Mφs in the early stage, and rapid release of 26SCS in the early and middle stages (within the concentration range of 1–3 mg/mL) induced a positive inflammatory response; initiated the pro-inflammatory reaction of Mφs within 3 days; shifted M1 Mφs to the M2 phenotype within 3–7 days; and significantly up-regulated the expression of two typical angiogenic growth factors, namelyVEGFandPDGF-BB, on day 7, leading to rapid HUVEC migration and angiogenesis. In vivo data also demonstrated that on the 14th day after surgery, the 26SCS-SilMA/Col-330-implanted areas exhibited less inflammation, faster re-epithelialization, more abundant collagen deposition and a greater number of blood vessels in the skin tissue. The composite sponges with higher 26SCS contents (the (5.0) 26SCS-SilMA/Col-330 and the (7.5) 26SCS-SilMA/Col-330) could better orchestrate the phenotype and function of Mφs and facilitate wound healing. These findings highlight that the 26SCS-SilMA/Col-330 sponges developed in this work might have great potential as a novel dressing for the treatment of diabetic wounds.
研究领域:
生物医学工程
·
组织工程
·
伤口愈合
·
炎症
·
血管生成
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Zhao Jian,Zhang Haoqian,Ling Zhengyun,An Ziyan,Xiao Shuwei,Wang Pengchao,Fu Zhouyang,Shao Jinpeng,Sun Yanfeng,Fu Weijun
Bladder tissue engineering holds promise for addressing bladder defects resulting from congenital or acquired bladder diseases. However, inadequate vascularization significantly impacts the survival and function of engineered tissues after transplantation. Herein, a novel bilayer silk fibroin (BSF) scaffold was fabricated with the capability of vascular endothelial growth factor (VEGF) and platelet derived growth factor-BB (PDGF-BB) sequential release. The outer layer of the scaffold was composed of compact SF film with waterproofness to mimic the serosa of the bladder. The inner layer was constructed of porous SF matrix incorporated with SF microspheres (MS) loaded with VEGF and PDGF-BB. We found that the 5% (w/v) MS-incorporated scaffold exhibited a rapid release of VEGF, whereas the 0.2% (w/v) MS-incorporated scaffold demonstrated a slow and sustained release of PDGF-BB. The BSF scaffold exhibited good biocompatibility and promoted endothelial cell migration, tube formation and enhanced endothelial differentiation of adipose derived stem cells (ADSCs) in vitro. The BSF patch was constructed by seeding ADSCs on the BSF scaffold. After in vivo transplantation, not only could the BSF patch facilitate the regeneration of urothelium and smooth muscle, but more importantly, stimulate the regeneration of blood vessels. This study demonstrated that the BSF patch exhibited excellent vascularization capability in bladder reconstruction and offered a viable functional bioengineered patch for future clinical studies.
研究领域:
组织工程
·
生物医学工程
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2022
·Vol. 50
·期 3
·1-13
·
IF 5.314
Zhen Shen,Wei Dong,Zehua Chen,Guoqian Chen,Yan Zhang,Zige Li,Haixiong Lin,Huamei Chen,Minling Huang,Ying Guo,Ziwei Jiang
Total flavonoids of Rhizoma Drynariae (TFRD), extracted from the kidney‑tonifying Traditional Chinese medicine Rhizoma Drynariae, can be effective in treating osteoporosis, bone fractures and defects. However, the pharmacological effects of TFRD on the specific vessel subtype CD31hiEmcnhi during distraction osteogenesis (DO) remains unclear. The present study aimed to investigate the effects of TFRD on CD31hiEmcnhi vessels in a rat model of DO. In the present study, tibial DO models were established using 60 rats with a distraction rate of 0.2 mm per day for 20 days. Co‑immunofluorescence staining of CD31 and endomucin (Emcn) was conducted to determine CD31hiEmcnhi vessels. Radiographic, angiographic and histological analyses were performed to assess bone and vessel formation. Tube formation, alkaline phosphatase (ALP) and Von Kossa staining assays were performed to test angiogenesis of endothelial precursor cells (EPCs) and osteogenesis of bone marrow‑derived mesenchymal stem cells (BMSCs). Additionally, expression levels of platelet‑derived growth factor (PDGF)‑BB, VEGF, runt‑related transcription factor 2 (RUNX2) and Osterix (OSX) were determined by western blotting and reverse transcription‑quantitative PCR. The in vivo assays demonstrated that TFRD markedly promoted CD31hiEmcnhi vessel formation during DO, whereas PDGF‑BB neutralizing antibody suppressed vessel formation. Furthermore, the ALP, Von Kossa staining and tube formation assays indicated that TFRD notably elevated the angiogenic capacity of EPCs and osteogenic capacity of BMSCs under stress conditions, which was significantly suppressed by blocking PDGF‑BB. The protein and mRNA levels of PDGF‑BB, VEGF, RUNX2 and OSX were upregulated by TFRD, but downregulated by blocking PDGF‑BB. Thus, TFRD could facilitate CD31hiEmcnhi vessel formation and subsequently enhance angiogenic‑osteogenic coupling to regenerate bone defects during DO via the PDGF‑BB/VEGF/RUNX2/OSX signaling axis, which indicated that CD31hiEmcnhi vessels could be a potential novel therapeutic target for DO, and TFRD may represent a promising drug for promoting bone regeneration in DO by increasing CD31hiEmcnhi vessels.
研究领域:
药理学
·
骨科
·
分子生物学
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2022
·Vol. 12
·期 1
·2201661
·
IF 11.092
Zonghan Xu,Liang Wu,Yu Tang,Kun Xi,Jincheng Tang,Yichang Xu,Jingzhi Xu,Jian Lu,Kaijin Guo,Yong Gu,Liang Chen
The bone immune microenvironment (BIM) regulates bone regeneration and affects the prognosis of fractures. However, there is currently no effective strategy that can precisely modulate macrophage polarization to improve BIM for bone regeneration. Herein, a hybridized biphasic bionic periosteum, inspired by the BIM and functional structure of the natural periosteum, is presented. The gel phase is composed of genipin-crosslinked carboxymethyl chitosan and collagen self-assembled hybrid hydrogels, which act as the “dam” to intercept IL-4 released during the initial burst from the bionic periosteum fiber phase, thus maintaining the moderate inflammatory response of M1 macrophages for mesenchymal stem cell recruitment and vascular sprouting at the acute fracture. With the degradation of the gel phase, released IL-4 cooperates with collagen to promote the polarization towards M2 macrophages, which reconfigure the local microenvironment by secreting PDGF-BB and BMP-2 to improve vascular maturation and osteogenesis twofold. In rat cranial defect models, the controlled regulation of the BIM is validated with the temporal transition of the inflammatory/anti-inflammatory process to achieve faster and better bone defect repair. This strategy provides a drug delivery system that constructs a coordinated BIM, so as to break through the predicament of the contradiction between immune response and bone tissue regeneration.
研究领域:
组织工程
·
再生医学
·
免疫学
·
生物医学工程
·
骨生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBON
·
2018
·
IF 7.082
Jingwen Gao,Huiwen Xiong,Wei Zhang,Ying Wang,Hangxing Wang,Wei Wen,Xiuhua Zhang,Shengfu Wang
Here, an electrochemiluminescent aptasensor based on β-cyclodextrin/graphitic carbon nitride (β-CD/g-C 3 N 4 ) composite for selective and highly ultrasensitive assay of platelet derived growth factor BB (PDGF-BB) is fabricated. To achieve the sensitive and specific detection of PDGF-BB, it is an available strategy to explore excellent electrochemiluminescent (ECL) luminophores with the advantages of high electrochemical-driven luminescent activity and a specific recognition function. In this work, for the first time a novel β-CD non-covalently functionalized g-C 3 N 4 composite β-CD/g-C 3 N 4 was employed to construct the ECL detection platform for PDGF-BB based on its aptamer. The limit of detection was determined to be as low as 2.6 × 10 −13 g/mL. It was observed that β-CD was playing a key role in improving the adamantane-labeled DNA amount modified on the electrode surface. It can further help to amplify the ECL quenching effect by both energy transfer and photo-excited electron transfer processes between g-C 3 N 4 emitter and ferrocene quencher. It is anticipated that β-CD/g-C 3 N 4 may be a class of promising material for constructing ECL sensors.
研究领域:
分析化学
·
生物传感器
·
材料科学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）