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Stromal cell-derived factor-1α regulates chondrogenic differentiation via activation of the Wnt/β-catenin pathway in mesenchymal stem cells 被引量:2
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作者 Xiao Chen Xia-Ming Liang +1 位作者 Jia Zheng Yong-Hui Dong 《World Journal of Stem Cells》 SCIE 2023年第5期490-501,共12页
BACKGROUND Mesenchymal stem cells(MSCs)have been applied to treat degenerative articular diseases,and stromal cell-derived factor-1α(SDF-1α)may enhance their therapeutic efficacy.However,the regulatory effects of SD... BACKGROUND Mesenchymal stem cells(MSCs)have been applied to treat degenerative articular diseases,and stromal cell-derived factor-1α(SDF-1α)may enhance their therapeutic efficacy.However,the regulatory effects of SDF-1αon cartilage differentiation remain largely unknown.Identifying the specific regulatory effects of SDF-1αon MSCs will provide a useful target for the treatment of degenerative articular diseases.AIM To explore the role and mechanism of SDF-1αin cartilage differentiation of MSCs and primary chondrocytes.METHODS The expression level of C-X-C chemokine receptor 4(CXCR4)in MSCs was assessed by immunofluorescence.MSCs treated with SDF-1αwere stained for alkaline phosphatase(ALP)and with Alcian blue to observe differentiation.Western blot analysis was used to examine the expression of SRY-box transcription factor 9,aggrecan,collagen II,runt-related transcription factor 2,collagen X,and matrix metalloproteinase(MMP)13 in untreated MSCs,of aggrecan,collagen II,collagen X,and MMP13 in SDF-1α-treated primary chondrocytes,of glycogen synthase kinase 3β(GSK3β)p-GSK3βandβ-catenin expression in SDF-1α-treated MSCs,and of aggrecan,collagen X,and MMP13 in SDF-1α-treated MSCs in the presence or absence of ICG-001(SDF-1αinhibitor).RESULTS Immunofluorescence showed CXCR4 expression in the membranes of MSCs.ALP stain was intensified in MSCs treated with SDF-1αfor 14 d.The SDF-1αtreatment promoted expression of collagen X and MMP13 during cartilage differentiation,whereas it had no effect on the expression of collagen II or aggrecan nor on the formation of cartilage matrix in MSCs.Further,those SDF-1α-mediated effects on MSCs were validated in primary chondrocytes.SDF-1αpromoted the expression of p-GSK3βandβ-catenin in MSCs.And,finally,inhibition of this pathway by ICG-001(5μmol/L)neutralized the SDF-1α-mediated up-regulation of collagen X and MMP13 expression in MSCs.CONCLUSION SDF-1αmay promote hypertrophic cartilage differentiation in MSCs by activating the Wnt/β-catenin pathway.These findings provide further evidence for the use of MSCs and SDF-1αin the treatment of cartilage degeneration and osteoarthritis. 展开更多
关键词 Stromal cell-derived factor-1α Mesenchymal stem cells chondrogenic differentiation WNT/Β-CATENIN C-X-C chemokine receptor 4
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Chondrogenic Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells Induced by Cartilage-derived Morphogenetic Protein-2 In Vitro 被引量:11
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作者 田洪涛 杨述华 +2 位作者 徐亮 张宇坤 许伟华 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2007年第4期429-432,共4页
To study the cartilage differentiation of mouse mesenchymal stem cells (MSCs) induced by cartilage-derived morphogenetic proteins-2 in vitro, the MSCs were isolated from mouse bone marrow and cultured in vitro. The ... To study the cartilage differentiation of mouse mesenchymal stem cells (MSCs) induced by cartilage-derived morphogenetic proteins-2 in vitro, the MSCs were isolated from mouse bone marrow and cultured in vitro. The cells in passage 3 were induced into chondrogenic differentiation with different concentrations of recombinant human cartilage-derived morphogenetic proteins-2 (0, 10, 20, 50 and 100 ng/mL). After 14 days of induction, morphology of cells was observed under phase-contrast microscope. Collagen Ⅱ mRNA and protein were examined with RT-PCR, Western blotting and immunocytochemistry respectively and the sulfate glycosaminoglycan was measured by Alcian blue staining. RT-PCR showed that CDMP-2 could promote expression of collagen Ⅱ mRNA in an dose-dependant manner, especially at the concentration of 50 ng/mL and 100 ng/mL. Immunocytochemistry and Western blotting revealed a similar change. Alcian blue staining exhibited deposition of typical cartilage extracellular matrix. Our results suggest that mouse bone marrow mesencymal stem cells can differentiate into chondrogenic phonotype with the induction of CDMP-2 in vitro, which provides a basis for further research on the role of CDMP-2 in chondrogenesis. 展开更多
关键词 cartilage-derived morphogenetic proteins-2 bone marrow mesenchymal stem cell chondrogenic differentiation MOUSE
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Chondrogenic differentiation of rat bone marrow mesenchymal stem cells induced by puerarin and tetrandrine 被引量:1
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作者 Xin-Ran Dong Meng-Jiao Hu +2 位作者 Hui-Xin Pan Ke-Feng Li Yuan-Lu Cui 《Acupuncture and Herbal Medicine》 2022年第2期130-138,共9页
Objective: This study aims to clarify the effect of the active components puerarin and tetrandrine on the chondrogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).Methods: Using network pharmacology, ... Objective: This study aims to clarify the effect of the active components puerarin and tetrandrine on the chondrogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).Methods: Using network pharmacology, protein targets of puerarin and tetrandrine were predicted, and a database of cartilage formation targets was established. The protein target information related to disease was then collected, and the drug-targeting network was constructed by analyzing the protein–protein interactions. Genes related to chondrogenesis induced by puerarin and tetrandrine and chondroblast differentiation signaling pathways were searched. Finally, potential drug-and disease-related genes,as well as proteins, were screened and verified using real-time RT-PCR and western blotting.Results: Network pharmacological studies have shown that puerarin and tetrandrine are involved in BMSCs cartilage differentiation. The experimental results showed that puerarin and tetrandrine could regulate the expression of cartilage differentiation-related genes and proteins. Puerarin increased the protein expression of COL2 A1, COL10 A1, MMP13, and SOX-9,as well as the gene expression of Col2 a1, Mmp13, Tgfb1, and Sox-9. Tetrandrine increased the protein expression of COL2 A1,COL10 A1, MMP13, and SOX-9, as well as the gene expression of Col10 a1, Tgfb1, Sox-9, and Acan. The combination of puerarin and tetrandrine increased the protein expression of COL2 A1, COL10 A1, MMP13, and SOX-9 and the gene expression of Col2 a1,Col10 a1, Sox-9, and Acan.Conclusions: Puerarin, tetrandrine, and their combination can promote the proliferation of BMSCs and induce their differentiation into chondrocytes, and they are thus expected to be inducers of chondrogenic differentiation. These results suggest that puerarin and tetrandrine have potential therapeutic effects on osteoarthritis. 展开更多
关键词 Bone marrow mesenchymal stem cells(BMSCs) chondrogenic differentiation Network pharmacology PUERARIN TETRANDRINE
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Tumor necrosis factor-αinhibition restores matrix formation by human adipose-derived stem cells in the late stage of chondrogenic differentiation
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作者 Jiang-Tao Wan Xian-Shuai Qiu +2 位作者 Zhuo-Hang Fu Yong-Can Huang Shao-Xiong Min 《World Journal of Stem Cells》 SCIE 2022年第11期798-814,共17页
BACKGROUND Cartilage tissue engineering is a promising strategy for treating cartilage damage.Matrix formation by adipose-derived stem cells(ADSCs),which are one type of seed cell used for cartilage tissue engineering... BACKGROUND Cartilage tissue engineering is a promising strategy for treating cartilage damage.Matrix formation by adipose-derived stem cells(ADSCs),which are one type of seed cell used for cartilage tissue engineering,decreases in the late stage of induced chondrogenic differentiation in vitro,which seriously limits research on ADSCs and their application.AIM To improve the chondrogenic differentiation efficiency of ADSCs in vitro,and optimize the existing chondrogenic induction protocol.METHODS Tumor necrosis factor-alpha(TNF-α)inhibitor was added to chondrogenic culture medium,and then Western blotting,enzyme linked immunosorbent assay,immunofluorescence and toluidine blue staining were used to detect the cartilage matrix secretion and the expression of key proteins of nuclear factor kappa-B(NF-κB)signaling pathway.RESULTS In this study,we found that the levels of TNF-αand matrix metalloproteinase 3 were increased during the chondrogenic differentiation of ADSCs.TNF-αthen bound to its receptor and activated the NF-κB pathway,leading to a decrease in cartilage matrix synthesis and secretion.Blocking TNF-αwith its inhibitors etanercept(1μg/mL)or infliximab(10μg/mL)significantly restored matrix formation.CONCLUSION Therefore,this study developed a combination of ADSC therapy and targeted anti-inflammatory drugs to optimize the chondrogenesis of ADSCs,and this approach could be very beneficial for translating ADSC-based approaches to treat cartilage damage. 展开更多
关键词 Adipose-derived mesenchymal stem cells Human adipose-derived mesenchymal stem cells chondrogenic differentiation Tumor necrosis factor-alpha ETANERCEPT INFLIXIMAB Nuclear factor kappa-B
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Chondrogenic differentiation of human bone mesenchymal stem cells treated with growth differentiation factor 5 under hypoxia
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作者 张波 《外科研究与新技术》 2011年第2期129-130,共2页
Objective To explore the feasibility and effectiveness of the self-assembly cartilage tissue engineered with chondrogenically differentiated human bone mesenchymal stem cells (hBMCs) induced by growth differentiation ... Objective To explore the feasibility and effectiveness of the self-assembly cartilage tissue engineered with chondrogenically differentiated human bone mesenchymal stem cells (hBMCs) induced by growth differentiation factor-5 (GDF-5) 展开更多
关键词 BONE chondrogenic differentiation of human bone mesenchymal stem cells treated with growth differentiation factor 5 under hypoxia
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Ion elemental-optimized layered double hydroxide nanoparticles promote chondrogenic differentiation and intervertebral disc regeneration of mesenchymal stem cells through focal adhesion signaling pathway
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作者 Zhaojie Wang Huiyi Yang +5 位作者 Xu Xu Hongxing Hu Yuxin Bai Jian Hai Liming Cheng Rongrong Zhu 《Bioactive Materials》 SCIE CSCD 2023年第4期75-90,共16页
Chronic low back pain and dyskinesia caused by intervertebral disc degeneration(IDD)are seriously aggravated and become more prevalent with age.Current clinical treatments do not restore the biological structure and i... Chronic low back pain and dyskinesia caused by intervertebral disc degeneration(IDD)are seriously aggravated and become more prevalent with age.Current clinical treatments do not restore the biological structure and inherent function of the disc.The emergence of tissue engineering and regenerative medicine has provided new insights into the treatment of IDD.We synthesized biocompatible layered double hydroxide(LDH)nanoparticles and optimized their ion elemental compositions to promote chondrogenic differentiation of human umbilical cord mesenchymal stem cells(hUC-MSCs).The chondrogenic differentiation of LDH-treated MSCs was validated using Alcian blue staining,qPCR,and immunofluorescence analyses.LDH-pretreated hUC-MSCs were differentiated prior to transplantation into the degenerative site of a needle puncture IDD rat model.Repair and regeneration evaluated using X-ray,magnetic resonance imaging,and tissue immunostaining 4-12 weeks after transplantation showed recovery of the disc space height and integrated tissue structure.Transcriptome sequencing revealed significant regulatory roles of the extracellular matrix(ECM)and integrin receptors of focal adhesion signaling pathway in enhancing chondrogenic differentiation and thus prompting tissue regeneration.The construction of ion-specific LDH nanomaterials for in situ intervertebral disc regeneration through the focal adhesion signaling pathway provides theoretical basis for clinical transformation in IDD treatment. 展开更多
关键词 Mesenchymal stem cells Layered double hydroxide chondrogenic differentiation Intervertebral disc degeneration Focal adhesion signaling pathway
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Sulfated GAG mimetic peptide nanofibers enhance chondrogenic differentiation of mesenchymal stem cells in 3D in vitro models
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作者 Seher Yaylaci Mustafa O.Guler Ayse B.Tekinay 《Regenerative Biomaterials》 SCIE EI CSCD 2023年第1期29-39,共11页
Articular cartilage,which is exposed to continuous repetitive compressive stress,has limited self-healing capacity in the case of trauma.Thus,it is crucial to develop new treatment options for the effective regenerati... Articular cartilage,which is exposed to continuous repetitive compressive stress,has limited self-healing capacity in the case of trauma.Thus,it is crucial to develop new treatment options for the effective regeneration of the cartilage tissue.Current cellular therapy treatment options are microfracture and autologous chondrocyte implantation;however,these treatments induce the formation of fibrous cartilage,which degenerates over time,rather than functional hyaline cartilage tissue.Tissue engineering studies using biodegradable scaffolds and autologous cells are vital for developing an effective long-term treatment option.3D scaffolds composed of glycosaminoglycan-like peptide nanofibers are synthetic,bioactive,biocompatible,and biodegradable and trigger cell-cell interactions that enhance chondrogenic differentiation of cells without using any growth factors.We showed differentiation of mesenchymal stem cells into chondrocytes in both 2D and 3D culture,which produce a functional cartilage extracellular matrix,employing bioactive cues integrated into the peptide nanofiber scaffold without adding exogenous growth factors. 展开更多
关键词 peptide amphiphile nanofibers in vitro chondrogenic differentiation mesenchymal stem cells 3D cell culture
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Sox9 augments BMP2-induced chondrogenic differentiation by downregulating Smad7 in mesenchymal stem cells(MSCs) 被引量:9
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作者 Chen Zhao Wei Jiang +15 位作者 Nian Zhou Junyi Liao Mingming Yang Ning Hu Xi Liang Wei Xu Hong Chen Wei Liu Lewis L.Shi Leonardo Oliveira Jennifer Moriatis Wolf Sherwin Ho Aravind Athiviraham H.M.Tsai Tong-Chuan He Wei Huang 《Genes & Diseases》 SCIE 2017年第4期229-239,共11页
Cartilage injuries caused by arthritis or trauma pose formidable challenges for effective clinical management due to the limited intrinsic proliferative capability of chondrocytes.Autologous stem cell-based therapies ... Cartilage injuries caused by arthritis or trauma pose formidable challenges for effective clinical management due to the limited intrinsic proliferative capability of chondrocytes.Autologous stem cell-based therapies and transgene-enhanced cartilage tissue engineering may open new avenues for the treatment of cartilage injuries.Bone morphogenetic protein 2(BMP2)induces effective chondrogenesis of mesenchymal stem cells(MSCs)and can thus be explored as a potential therapeutic agent for cartilage defect repair.However,BMP2 also induces robust endochondral ossification.Although the precise mechanisms through which BMP2 governs the divergence of chondrogenesis and osteogenesis remain to be fully understood,blocking endochondral ossification during BMP2-induced cartilage formation may have practical significance for cartilage tissue engineering.Here,we investigate the role of Sox9-donwregulated Smad7 in BMP2-induced chondrogenic differentiation of MSCs.We find that overexpression of Sox9 leads to a decrease in BMP2-induced Smad7 expression in MSCs.Sox9 inhibits BMP2-induced expression of osteopontin while enhancing the expression of chondrogenic marker Col2a1 in MSCs.Forced expression of Sox9 in MSCs promotes BMP2-induced chondrogenesis and suppresses BMP2-induced endochondral ossification.Constitutive Smad7 expression inhibits BMP2-induced chondrogenesis in stem cell implantation assay.Mouse limb explant assay reveals that Sox9 expands BMP2-stimulated chondrocyte proliferating zone while Smad7 promotes BMP2-intitated hypertrophic zone of the growth plate.Cell cycle analysis indicates that Smad7 induces significant early apoptosis in BMP2-stimulated MSCs.Taken together,our results strongly suggest that Sox9 may facilitate BMP2-induced chondrogenesis by downregulating Smad7,which can be exploited for effective cartilage tissue engineering. 展开更多
关键词 Bone morphogenetic protein 2(BMP2) Cartilage tissue engineering chondrogenic differentiation Endochondral ossification Mesenchymal stem cells(MSCs) SMAD7 SOX9
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Tetrahedral framework nucleic acids enhance the chondrogenic potential of human umbilical cord mesenchymal stem cells via the PI3K/AKT axis
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作者 Liwei Fu Pinxue Li +10 位作者 Jiang Wu Yazhe Zheng Chao Ning Zhiyao Liao Xun Yuan Zhengang Ding Zhichao Zhang Xiang Sui Sirong Shi Shuyun Liu Quanyi Guo 《Regenerative Biomaterials》 SCIE EI CSCD 2023年第1期1552-1565,共14页
The field of regenerative medicine faces a notable challenge in terms of the regeneration of articular cartilage.Without proper treatment,it can lead to osteoarthritis.Based on the research findings,human umbilical co... The field of regenerative medicine faces a notable challenge in terms of the regeneration of articular cartilage.Without proper treatment,it can lead to osteoarthritis.Based on the research findings,human umbilical cord mesenchymal stem cells(hUMSCs)are considered an excellent choice for regenerating cartilage.However,there is still a lack of suitable biomaterials to control their ability to self-renew and differentiate.To address this issue,in this study using tetrahedral framework nucleic acids(tFNAs)as a new method in an in vitro culture setting to manage the behaviour of hUMSCs was proposed.Then,the influence of tFNAs on hUMSC proliferation,migration and chondrogenic differentiation was explored by combining bioinformatics methods.In addition,a variety of molecular biology techniques have been used to investigate deep molecular mechanisms.Relevant results demonstrated that tFNAs can affect the transcriptome and multiple signalling pathways of hUMSCs,among which the PI3K/Akt pathway is significantly activated.Furthermore,tFNAs can regulate the expression levels of multiple proteins(GSK3β,RhoA and mTOR)downstream of the PI3K-Akt axis to further enhance cell proliferation,migration and hUMSC chondrogenic differentiation.tFNAs provide new insight into enhancing the chondrogenic potential of hUMSCs,which exhibits promising potential for future utilization within the domains of AC regeneration and clinical treatment. 展开更多
关键词 tFNAs articular cartilage hUMSCs chondrogenic differentiation
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Nanosecond pulsed electric fields prime mesenchymal stem cells to peptide ghrelin and enhance chondrogenesis and osteochondral defect repair in vivo 被引量:4
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作者 Kejia Li Litong Fan +6 位作者 Jianjing Lin Boon Chin Heng Zhantao Deng Qiujian Zheng Jue Zhang Yangzi Jiang Zigang Ge 《Science China(Life Sciences)》 SCIE CAS CSCD 2022年第5期927-939,共13页
Mesenchymal stem cells(MSCs) are important cell sources in cartilage tissue development and homeostasis,and multiple strategies have been developed to improve MSCs chondrogenic differentiation with an aim of promoting... Mesenchymal stem cells(MSCs) are important cell sources in cartilage tissue development and homeostasis,and multiple strategies have been developed to improve MSCs chondrogenic differentiation with an aim of promoting cartilage regeneration.Here we report the effects of combining nanosecond pulsed electric fields(ns PEFs) followed by treatment with ghrelin(a hormone that stimulates release of growth hormone) to regulate chondrogenesis of MSCs.ns PEFs and ghrelin were observed to separately enhance the chondrogenesis of MSCs,and the effects were significantly enhanced when the bioelectric stimulation and hormone were combined,which in turn improved osteochondral tissue repair of these cells within Sprague Dawley rats.We further found that ns PEFs can prime MSCs to be more receptive to subsequent stimuli of differentiation by upregulated Oct4/Nanog and activated JNK signaling pathway.Ghrelin initiated chondrogenic differentiation by activation of ERK1/2 signaling pathway,and RNA-seq results indicated 243 genes were regulated,and JAK-STAT signaling pathway was involved.Interestingly,the sequential order of applying these two stimuli is critical,with ns PEFs pretreatment followed by ghrelin enhanced chondrogenesis of MSCs in vitro and subsequent cartilage regeneration in vivo,but not vice versa.This synergistic prochondrogenic effects provide us new insights and strategies for future cell-based therapies. 展开更多
关键词 mesenchymal stem cells nanosecond pulsed electric fields GHRELIN chondrogenic differentiation
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Tetrahedral framework nucleic acids promote the biological functions and related mechanism of synovium-derived mesenchymal stem cells and show improved articular cartilage regeneration activity in situ 被引量:3
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作者 Liwei Fu Pinxue Li +13 位作者 Junyao Zhu Zhiyao Liao Cangjian Gao Hao Li Zhen Yang Tianyuan Zhao Wei Chen Yu Peng Fuyang Cao Chao Ning Xiang Sui Quanyi Guo Yunfeng Lin Shuyun Liu 《Bioactive Materials》 SCIE 2022年第3期411-427,共17页
Many recent studies have shown that joint-resident mesenchymal stem cells(MSCs)play a vital role in articular cartilage(AC)in situ regeneration.Specifically,synovium-derived MSCs(SMSCs),which have strong chondrogenic ... Many recent studies have shown that joint-resident mesenchymal stem cells(MSCs)play a vital role in articular cartilage(AC)in situ regeneration.Specifically,synovium-derived MSCs(SMSCs),which have strong chondrogenic differentiation potential,may be the main driver of cartilage repair.However,both the insufficient number of MSCs and the lack of an ideal regenerative microenvironment in the defect area will seriously affect the regeneration of AC.Tetrahedral framework nucleic acids(tFNAs),notable novel nanomaterials,are considered prospective biological regulators in biomedical engineering.Here,we aimed to explore whether tFNAs have positive effects on AC in situ regeneration and to investigate the related mechanism.The results of in vitro experiments showed that the proliferation and migration of SMSCs were significantly enhanced by tFNAs.In addition,tFNAs,which were added to chondrogenic induction medium,were shown to promote the chondrogenic capacity of SMSCs by increasing the phosphorylation of Smad2/3.In animal models,the injection of tFNAs improved the therapeutic outcome of cartilage defects compared with that of the control treatments without tFNAs.In conclusion,this is the first report to demonstrate that tFNAs can promote the chondrogenic differentiation of SMSCs in vitro and enhance AC regeneration in vivo,indicating that tFNAs may become a promising therapeutic for AC regeneration. 展开更多
关键词 Tetrahedral framework nucleic acids Articular cartilage regeneration Mesenchymal stem cells chondrogenic differentiation
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Synthesis of photo-reactive poly(vinyl alcohol)and construction of scaffold-free cartilage like pellets in vitro 被引量:1
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作者 Bao Li Yongli Gao +5 位作者 Likun Guo Yujiang Fan Naoki Kawazoe Hongsong Fan Xingdong Zhang Guoping Chen 《Regenerative Biomaterials》 SCIE 2018年第3期159-166,共8页
Photo-reactive poly(vinyl alcohol)(PRPVA)was synthesized by introduction of phenyl azido groups into poly(vinyl alcohol)(PVA)and applied for surface modification.PRPVA was grafted onto cell culture plate surface homog... Photo-reactive poly(vinyl alcohol)(PRPVA)was synthesized by introduction of phenyl azido groups into poly(vinyl alcohol)(PVA)and applied for surface modification.PRPVA was grafted onto cell culture plate surface homogeneously or in a micropattern.Human mesenchymal stem cells(hMSCs)cultured on cell culture plate surface and PVA-modified surface showed different behaviors.Cells adhered and spread well on cell culture plate surface,while they did not adhere on PVA-grafted surface at all.When hMSCs were cultured on PVA-micropatterned surface,they formed a cell micropattern.Cells formed pellets after cultured on PVA homogeneously modified surface in chondrogenic induction medium for 2 weeks.The pellets were positively stained by hematoxylin/eosin,safranin-O/fast green and toluidin blue,and they were also stained brown by Type II collagen and proteoglycan immunohistological staining.Real-time PCR analysis was conducted to investigate the expression of colI,colII,colX,aggrecan and sox9 mRNA.Results of gene expression were in agreement with those of histological and immunohistological observations.These results indicated that hMSCs cultured on PVA-modified surface performed chondrogenic differentiation,and it was possible to construct scaffold-free cartilage like pellets with PVA-modified surface in vitro. 展开更多
关键词 surface modification photo-reactive poly(vinyl alcohol) chondrogenic differentiation
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