Drug Design Development and Therapy
·
2024
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IF 4.7
Chaoying Jin,Ruolin Zhao,Weihang Hu,Xiaolong Wu,Li Zhou,Letian Shan,Huiling Wu
Background Pressure ulcer is common in the bedridden elderly with high mortality and lack of effective treatment. In this study, human-adipose-derived-stem-cells-hyaluronic acid gel (hADSCs-HA gel) was developed and applied topically to treat pressure ulcers, of which efficacy and paracrine mechanisms were investigated through in vivo and in vitro experiments.Methods Pressure ulcers were established on the backs of C57BL/6 mice and treated topically with hADSCs-HA gel, hADSCs, hyaluronic acid, and normal saline respectively. The rate of wound closure was observed continuously during the following 14 days and the wound samples were obtained for Western blot, histopathology, immunohistochemistry, and proteomic analysis. Human dermal fibroblasts (HDFs) and human venous endothelial cells (HUVECs) under normal or hypoxic conditions were treated with conditioned medium of human ADSCs (ADSC-CM), then CCK-8, scratch test, tube formation, and Western blot were conducted to evaluate the paracrine effects of hADSCs and to explore the underlying mechanism.Results The in vivo data demonstrated that hADSCs-HA gel significantly accelerated the healing of pressure ulcers by enhancing collagen expression, angiogenesis, and skin proliferation. The in vitro data revealed that hADSCs strengthened the proliferation and wound healing capabilities of HDFs and HUVECs, meanwhile promoted collagen secretion and tube formation through paracrine mode. ADSC-CM was also proved to exert protective effects on hypoxic HDFs and HUVECs. Besides, the results of proteomic analysis and Western blot elucidated that lipid metabolism and PPARβ/δ pathway mediated the healing effect of hADSCs-HA gel on pressure ulcers.Conclusion Our research showed that topical application of hADSCs-HA gel played an important role in dermal regeneration and angiogenesis. Therefore, hADSCs-HA gel exhibited the potential as a novel stem-cell-based therapeutic strategy of treating pressure ulcers in clinical practices.
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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伤口愈合
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产品关联
DOI
PubMed
高影响因子
TISSUE & CELL
·
2023
·
IF 2.6
Yujun Zhao,Xiaotie Wang,Keke Nie
Background Osteoarthritis is a main cause of deformity in aging people. The chondrogenesis of human adipose-derived stem cells (hADSCs) has a positive effect on the cure of osteoarthritis. However, the regulatory mechanism of hADSC chondrogenesis still needs further exploration. This research investigates the role of interferon regulatory factor 1 (IRF1) in the chondrogenesis of hADSCs. Methods hADSCs were purchased and cultured. The interaction between IRF1 and hypoxia inducible lipid droplet associated (HILPDA) was predicted by bioinformatics analysis, and verified through dual-luciferase reporter and chromatin immunoprecipitation assays. The expressions of IRF1 and HILPDA in osteoarthritis cartilage samples were measured through qRT-PCR. After hADSCs were transfected or further induced for chondrogenesis, the chondrogenesis was visualized by Alcian blue staining, and the expressions of IRF1, HILPDA and chondrogenesis-related factors (SOX9, Aggrecan , COL2A1, MMP13, MMP3) were determined through qRT-PCR or Western blot . Results HILPDA bound to IRF1 in hADSCs. IRF1 and HILPDA levels were up-regulated during the chondrogenesis of hADSCs. Overexpressions of IRF1 and HILPDA promoted the chondrogenesis of hADSCs with the up-regulation of SOX9 , Aggrecan and COL2A1 and the down-regulation of MMP13 and MMP3 ; however, IRF1 silencing generated the opposite effects. Besides, HILPDA overexpression reversed the effects of IRF1 silencing on inhibiting chondrogenesis of hADSCs and regulating the expressions of chondrogenesis-related factors. Conclusion IRF1 promotes the chondrogenesis of hADSCs through up-regulating HILPDA level, providing novel biomarkers for treating osteoarthritis.
研究领域:
干细胞生物学
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骨科
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Tissue Engineering Part A
·
2014
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IF 0
Shane Gao,Peng Zhao,Chao Lin,Yuxi Sun,Yilei Wang,Zhichong Zhou,Danjing Yang,Xianli Wang,Hongzhen Xu,Fei Zhou,Limei Cao,Wei Zhou,Ke Ning,Xu Chen,Jun Xu
Multipotent human adipose-derived stromal/stem cells (hADSCs) hold a great promise for cell-based therapy for many devastating human diseases, such as spinal cord injury and stroke. If exogenous hADSCs can be cultured in a three-dimensional (3D) scaffold with effective proliferation and differentiation capacity, it will better mimic the in vivo environment, which will have profound impact on the therapeutic application of hADSCs. In this study, a group of elastic-dominant, porous bioscaffolds from photocurable chitosan and gelatin were fabricated and proven to be biocompatible with both hADSCs and hADSC-derived neuron-like cells (hADSC-NLCs) in vitro. The identity of harvested hADSCs was confirmed by their positive immunostaining of mesenchymal stem cell surface markers, CD29, CD44, and CD105, and also positive expression of stem markers, Sox-2, Oct-4, c-Myc, Nanog, and Klf4. Their multipotency was further confirmed by trilineage differentiation of hADSCs toward adipocyte, osteoblast, and chondrocyte. It was found that hADSCs could be conditioned to differentiate into neurons in vitro as determined by immunostaining the markers of Tuj1, MAP2, NeuN, and Synapsin. The hADSCs and hADSC-NLCs were proven to be biocompatible with 3D scaffold, which actually facilitated the proliferation and differentiation of hADSCs in vitro, by MTT assay and their neuronal gene expression profiling. Moreover, hADSC-NLCs, which were mixed with 3D scaffold and transplanted into traumatic brain injury mouse model, survived in vivo and led to the better repair of the damaged brain area. The immunohistochemical studies revealed that 3D scaffold indeed improved the viability of transplanted cells, their ability to incorporate into the in vivo neural circuit, and their capacity for tissue repair. This study indicates that hADSCs would have great therapeutic application potential as seeding cells for in vivo transplantation to treat various neurological diseases when co-applied with porous chitosan/gelatin bioscaffolds.
研究领域:
再生医学
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干细胞研究
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组织工程
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神经科学
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产品关联
DOI
PubMed
Scientific Reports
·
2019
·Vol. 9
·期 1
·1-10
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IF 4.011
Wang Yaozong,Sun Naikun,Zhang Yinlong,Zhao Bin,Zhang Zheyi,Zhou Xu,Zhou Yuanyuan,Liu Hongyi,Zhang Ying,Liu Jianguo
This study explored the applicability, cellular efficacy, and osteogenic activities of porous nano-hydroxyapatite/Poly (glycerol sebacate)-grafted maleic anhydride (n-HA/PGS-g-M) composite scaffolds. Nuclear magnetic resonance (NMR) analyses indicated that approximately 43% of the hydroxide radicals in PGS were displaced by maleic anhydride. Resonance bands at 1036 cm −1 occurred in scaffolds containing nHA powders, and peak areas increased when n-HA weight increased in PGS-M-n-HA-0.4, PGS-M-n-HA-0.5, and PGS-M-n-HA-0.6 scaffolds. The n-HA/PGS-g-M composite scaffolds exhibited porous microstructure with average pore size of 150–300 µm in scanning electron microscopy (SEM) analysis. Differential scanning calorimetry (DSC) identified the glass transition temperature (Tg) as −25–30 °C, indicative of quality resilience. The modulus of compressibility increased when n-HA content increased. Interestingly, viability of human adipose-derived stem cells (hADSCs) in vitro and expression of the osteogenic related genes RUNX2 , OCN , and COL1A1 was enhanced in the n-HA/PGS-g-M composite scaffolds compared to those factors observed in PGS-g-M scaffolds. Finally, simulated body fluid (SBF) tests indicated more apatite deposits on the surface of n-HA/PGS-g-M scaffolds compared to PGS-g-M scaffolds. Overall, porous n-HA/PGS-g-M composite scaffolds possessed acceptable biocompatibility and mechanical properties, and they stimulated hADSC cell proliferation and differentiation. Given these qualities, the composite scaffolds have potential applications in bone tissue engineering.
研究领域:
组织工程
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生物材料科学
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干细胞研究
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材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
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2020
·Vol. 55
·期 27
·13216-13231
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IF 3.553
Huang Liqu,Wang Xianli,Zhang Yue,Cheng Zhaojun,Xue Feng,Guo Yunfei,Deng Yongji,Chu Chenglin,Tao Li,Bai Jing
Hypospadias is a common congenital malformation of the male urogenital system. As a recently arisen reconstruction method for hypospadias, polymer tissue engineering urethral scaffold often results in necrosis and other complications due to the lack of bioactivity. To improve the bioactivity of polymer, in this work, we prepared biodegradable Mg/poly(lactic-co-glycolic acid) (PLGA) composite nanofiber scaffolds by electrospun with 3, 6, and 9 wt.% of micron-scale Mg particles. The mechanical properties of the PLGA scaffold gradually decrease with the addition of Mg particles but still at an acceptable level. On the other hand, these composite scaffolds show very good biocompatibility and promotional bioactivity, namely non-cytotoxicity, gradual proliferation enhancement, and good adhesion state of human adipose stem cells (HADSCs) on the scaffold surface. Besides, through quantitative real-time polymerase chain reaction (qRT-PCR) test, different genes expression levels of human umbilical vein endothelial cells (HUVECs) were also gradually up-regulated with the increase in Mg content. The present results indicate that Mg containing PLGA scaffolds might not only have the potential to promote tissue regeneration related to urethral repair, but also stimulate endothelial cells to achieve vascularization and anti-inflammatory functions. Consequently, considering both the mechanical properties and bioactivity for clinical demand, the Mg/PLGA composite scaffolds with suitable Mg contents are promising for the regeneration of defective urethral tissues.
研究领域:
组织工程
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生物材料科学
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再生医学
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泌尿外科
✓ 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）