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| 1 | Matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 expression in fibrotic rat liver显示文摘INTRODUCTIONLiver fibrosis is an excessive deposition ofextracellular matrix(ECM)resulted from bothincreased synthesis and decreased degradation.Matrix metalloproteinases(MMPs)represent agroup of neutral proteinases with variable | Liu HL Li XH Wang DY Yang SP | 2000 | World Journal of Gastroenterology2000，6，6： | 31 |
| 2 | Effects of glycyrrhetinic acid on collagen metabolism of hepatic stellate cells at different stages of liver fibrosis in rats显示文摘INTRODUCTIONLiver fibrosis is a dynamic course leading tocirrhosis from a various chronic liver diseases. Thepathological basis of fibrosis is the disturbance ofproduction and degradation of the extracellularmatrix (ECM), which causes accumulation of ECMin the liver[1,2]. | Ji Yao Wang Qi Sheng Zhang Ji Sheng Guo Mei Yu Hu Department of Gastroenterology, Zhongshan Hospital, Medical Center, Fu Dan University Shanghai Medical University), Shanghai 200032, China | 2001 | World Journal of Gastroenterology2001，7，1： | 29 |
| 3 | The regulatory role of AT 1 receptor on activated HSCs in hepat,c fibrogenesis,effects of RAS inhibitors on hepatic fibrosis induced by CCl_4显示文摘AIM To assess the effect of ACE inhibitor andAng Ⅱ type Ⅰ(AT1)receptor antagonist inpreventing hepatic fibrosis caused by CCl4administration in rats;to investigate whether ornot there are expression of AT 1 receptors onhepatic stellate cells;and to observe the effectof Ang Ⅱ on proliferation and ECM synthesis ofcultured HSCs.METHODS Studies were conducted in maleSprague-Dawley rats.Except for thehepatofibrotic model group and the controlgroup,in three treated groups,either enalapril(5 mg/kg),or Iosartan(10 mg/kg),or enalapril+Iosartan were given to the fibrotic rats bydaily gavage,and saline vehicle was given tomodel and normal control rats.After 6 weeks,liver fibrosis was assessed directly by hepaticmorphometric analysis,which has beenconsidered the gold standard for thequantification of fibrosis.The expressions of AT1 receptors and(α-mooth muscle actin,α-SMA)in liver tissue or isolated hepatic stellate cells(HSCs)were detected by immunohistochemicaltechniques.The effect of Ang Ⅱ on HSCproliferation was determined by MTT method.Effect of Ang Ⅱ on collagen synthesis of HSCswas determined by 3H-proline incorporation.RESULTS Contrasted to the fibrosis in rats ofthe model group,groups of rats treated with either enalapril or Iosartan,or a combination oftwo drugs showed a limited expansion of theinterstitium(4.23±3.70 vs 11.22±4.79,P<0.05),but no difference was observedamong three treated groups(5.38±3.43,4.96±2.96,4.23±2.70,P>0.05).Expression of AT 1receptors was found in fibrotic interstitium offibrotic rats,whereas in normal control rats theywere limited to vasculature only to a very slightdegree.AT 1 receptors were also expressed onactivated HSCs in the culture.At concentrationsfrom 10-9to 10-5mol/L,Ang Ⅱ stimulated HSCproliferation in culture in a dose-dependentmanner.Increasing Ang Ⅱ concentrationsproduced corresponding increases in 3H-prolineincorporation.Differences among groups were significant.CONCLUSION Angiotensin-converting enzyme inhibitors and AT I blocker may slow the progression of hepatic fibrosis; activated HSCs express AT 1 receptors, and Ang Ⅱ can stimulate the proliferation and collagen synthesis of HSCs in a dose-dependent manner; and activation of RAS may be related to hepatic fibrogenesis induced by CCI4. | Hong Shan Wei Han Ming Lu Ding Guo Li Yu Tao Zhan Zhi Rong Wang Xin Huang Ji Lin Cheng Qin Fang Xu Department of Gastroenterology,Xinhua Hospital,Shanghai Second Medical University,Shanghai 200092,China | 2000 | World Journal of Gastroenterology2000，6，6： | 27 |
| 4 | Smart scaffolds in bone tissue engineering: A systematic review of literature显示文摘AIM: To improve osteogenic differentiation and attachment of cells.METHODS: An electronic search was conducted inPub Med from January 2004 to December 2013. Studies which performed smart modifications on conventional bone scaffold materials were included. Scaffolds with controlled release or encapsulation of bioactive molecules were not included. Experiments which did not investigate response of cells toward the scaffold(cell attachment, proliferation or osteoblastic differentiation) were excluded. RESULTS: Among 1458 studies, 38 met the inclusion and exclusion criteria. The main scaffold varied extensively among the included studies. Smart modifications included addition of growth factors(group Ⅰ-11 studies), extracellular matrix-like molecules(group Ⅱ-13 studies) and nanoparticles(nano-HA)(group Ⅲ-17 studies). In all groups, surface coating was the most commonly applied approach for smart modification of scaffolds. In group I, bone morphogenetic proteins were mainly used as growth factor stabilized on polycaprolactone(PCL). In group Ⅱ, collagen 1 in combination with PCL, hydroxyapatite(HA) and tricalcium phosphate were the most frequent scaffolds used. In the third group, nano-HA with PCL and chitosan were used the most. As variable methods were used, a thorough and comprehensible compare between the results and approaches was unattainable.CONCLUSION: Regarding the variability in methodology of these in vitro studies it was demonstrated that smart modification of scaffolds can improve tissue properties. | Saeed Reza Motamedian Sepanta Hosseinpour Mitra Ghazizadeh Ahsaie Arash Khojasteh | 2015 | World Journal of Stem Cells2015，7，3： | 15 |
| 5 | Prevention of Cistanche salsa Extract on Hepatic Fibrosis Induced by Carbon Tetrachloride in Rats显示文摘Objective To explore the antifibrotic effect of echinacoside on carbon tetrachloride(CCl4)-induced hepatic fibrosis in rats.Methods Male Wistar rats were randomly divided into normal control(n=8),model(n=14),and echinacoside treatment(n=14)groups.The hepatic fibrosis model was induced by CCl4compositor.The rats were ig administered with echinacoside at a daily dose of 50 mg/kg.The anti-oxidant status,liver function parameters,and hepatic hydroxyproline content were detected by chromatometry.The serum levels of hyaluronic acid(HA),type IV collagen(CIV),type III precollagen(PIIIP),and laminin(LN)were assayed with radioimmunoassay.The hpatic injury was detected by haematoxylin-eosine staining.The deposition of collagen was observed with Masson staining.Results Echinacoside increased the superoxide dismutase activity and reduced the levels of malondialdehyde,aspartate aminotransferase,alanine aminotransferase,HA,CIV,PIIIP,and LN in serum.Echinacoside could also reduce the hydroxyproline content in liver,alleviate hepatic injury,and inhibit collagen deposition.Conclusion Echinacoside possesses antihepatic fibrosis effect. | YANG Feng-rui WEN Du-su FANG Bu-wu LOU Jian-shi MENG Lin | 2013 | Chinese Herbal Medicines2013，5，3： | 10 |
| 6 | Role of matricellular proteins in cardiac tissue remodeling after myocardial infarction显示文摘After onset of myocardial infarction(MI),the left ventricle(LV) undergoes a continuum of molecular,cellular,and extracellular responses that result in LV wall thinning,dilatation,and dysfunction.These dynamic changes in LV shape,size,and function are termed cardiac remodeling.If the cardiac healing after MI does not proceed properly,it could lead to cardiac rupture or maladaptive cardiac remodeling,such as further LV dilatation and dysfunction,and ultimately death.Although the precise molecular mechanisms in this cardiac healing process have not been fully elucidated,this process is strictly coordinated by the interaction of cells with their surrounding extracellular matrix(ECM) proteins.The components of ECM include basic structural proteins such as collagen,elastin and specialized proteins such as fibronectin,proteoglycans and matricellular proteins.Matricellular proteins are a class of non-structural and secreted proteins that probably exert regulatory functions through direct binding to cell surface receptors,other matrix proteins,and soluble extracellular factors such as growth factors and cytokines.This small group of proteins,which includesosteopontin,thrombospondin-1/2,tenascin,periostin,and secreted protein,acidic and rich in cysteine,shows a low level of expression in normal adult tissue,but is markedly upregulated during wound healing and tissue remodeling,including MI.In this review,we focus on the regulatory functions of matricellular proteins during cardiac tissue healing and remodeling after MI. | Yutaka Matsui Junko Morimoto Toshimitsu Uede | 2010 | World Journal of Biological Chemistry2010，1，5： | 7 |
| 7 | Effects of transforming growth factor β2 and connective tissue growth factor on induction of epithelial mesenchymal transition and extracellular matrix synthesis in human lens epithelial cells显示文摘AIM:To Investigate the effects of transforming growth factorβ2(TGF-β2)and connective tissue growth factor(CTGF)on transdifferentiation of human lens epithelial cells(HLECs)cultured in vitro and synthesis of extracellular matrix(ECM).METHODS:HLECs were treated with TGF-β2(0,0.5,1.0,5,10μg/L)and CTGF(0,15,30,60,100μg/L)for different times(0,24,48,72h)in vitro and the expression ofα-smooth muscle actin(α-SMA),the main component of the extracellular matrix typeⅠcollagen(Col-1)and fibronectin(Fn)were measured by using real-time polymerase chain reaction(PCR)and western-blot.RESULTS:TGF-β2 and CTGF significantly increased expression ofα-SMA mRNA and protein(P<0.05,P<0.001),Fn mRNA and protein(P<0.001),Col-1 mRNA and protein(P<0.001).TGF-β2 could induce HLECs expression of CTGF mRNA and protein in dosedependent manner(P<0.05,P<0.001).TGF-β2 and CTGF could induce HLECs to expressα-SMA,Fn and Col-1 in time-dependent manner.Each time of TGF-β2and CTGF induced HELCs expression ofα-SMA,Fn,Col-1 mRNA and protein was significant increase compared with control(P<0.05,P<0.001).CONCLUSION:TGF-β2 and CTGF could induce HLECs epithelial mesenchymal transition and ECM synthesis. | Cheng Pei Bo Ma Qian-Yan Kang Li Qin Li-Jun Cui | 2013 | International Journal of Ophthalmology(English edition)2013，6，6： | 7 |
| 8 | Therapeutic strategies for peripheral nerve injury: decellularized nerve conduits and Schwann cell transplantation显示文摘In recent years, the use of Schwann cell transplantation to repair peripheral nerve injury has attracted much attention. Animal-based studies show that the transplantation of Schwann cells in combination with nerve scaffolds promotes the repair of injured peripheral nerves. Autologous Schwann cell transplantation in humans has been reported recently. This article reviews current methods for removing the extracellular matrix and analyzes its composition and function. The development and secretory products of Schwann cells are also reviewed. The methods for the repair of peripheral nerve injuries that use myelin and Schwann cell transplantation are assessed. This survey of the literature data shows that using a decellularized nerve conduit combined with Schwann cells represents an effective strategy for the treatment of peripheral nerve injury. This analysis provides a comprehensive basis on which to make clinical decisions for the repair of peripheral nerve injury. | Gong-Hai Han Jiang Peng Ping Liu Xiao Ding Shuai Wei Sheng Lu Yu Wang | 2019 | Neural Regeneration Research2019，14，8： | 6 |
| 9 | Relationship between expression of type Ⅲ collagen and phenotype of vascular smooth muscle cells in neointimal of stented coronary artery显示文摘To investigate the secretive features of type Ⅲ collagen in restenosis of the stented coronary artery and the relationship between the expression of type Ⅲ collagen and vascular smooth muscle cells (VSMCs) Methods An animal model of restenosis was established by implanting oversized tantalum stents into the coronary arteries in 26 dogs At the 7th, 14th and 28th days after implantation, the stented coronaries were harvested Transmission electronic microscopy and immunohistochemistry were employed to investigate the features of type Ⅲ collagen secretion and VSMCs’ phenotype The expression of type Ⅲ collagen was quantified and compared for the three stages Results Migration and proliferation of VSMCs were the main features at the 7th day after injury At the 14th day, proliferation of VSMCs reached the peak while much more secretion of collagen was noticeable VSMCs began to transform from the synthetic phenotype to the contractile phenotype at the 28th day, when a great quantity of collagen was also secreted The quantity of secreted type Ⅲ collagen was greater at the 14th and 28th day than that at the 7th day ( P <0 05) The stain density of type Ⅲ collagen was positively correlated to neointimal thickness at both of 14th and 28th day Conclusion The pathological bases of restenosis are variant in different period of restenosis formation Type Ⅲ collagen may play an important role in the late stage of restenosis after coronary | 向定成 黄大显 盖鲁粤 刘宏斌 | 2000 | Chinese Medical Journal2000，，4： | 4 |
| 10 | Fibroblasts, an inconspicuous but essential player in colon cancer development and progression显示文摘Tumor microenvironments have a crucial role in cancer initiation and progression, and share many molecular and pathological features with wound healing process. Unless treated, tumors, however, do not heal in contrast to wounds that heal within a limited time framework. Wounds heal in coordination of a myriad of types of cells, particularly endothelial cells, leukocytes, and fibroblasts. Similar sets of cells also contribute to cancer initiation and progression, and as a consequence, anti-cancer treatment strategies have been proposed and tested by targeting endothelial cells and/or leukocytes. Compared with endothelial cells and leukocytes, less attention has been paid to the roles of cancer-associated fibroblasts(CAFs), fibroblasts present in tumor tissues, because their heterogeneity hinders the elucidation on them at cellular and molecular levels. Here, we will discuss the origin of CAFs and their crucial roles in cancer initiation and progression, and the possibility to develop a novel type of anti-cancer treatment by manipulating the migration and functions of CAFs. | Naofumi Mukaida Soichiro Sasaki | 2016 | World Journal of Gastroenterology2016，22，23： | 4 |
| 11 | Effects of nanotopography on stem cell phenotypes显示文摘Stem cells are unspecialized cells that can self renew indefinitely and differentiate into several somatic cells given the correct environmental cues.In the stem cell niche,stem cell-extracellular matrix(ECM)interactions are crucial for different cellular functions,such as adhesion,proliferation,and differentiation.Recently, in addition to chemical surface modifications,the importance of nanometric scale surface topography and roughness of biomaterials has increasingly becoming recognized as a crucial factor for cell survival and host tissue acceptance in synthetic ECMs.This review describes the influence of nanotopography on stem cell phenotypes. | Rajeswari Ravichandran Clarisse CH Ng Casey K Chan Michael Raghunath Seeram Ramakrishna | 2009 | World Journal of Stem Cells2009，1，1： | 3 |
| 12 | Co-culture of tumor spheroids and monocytes in a collagen matrix-embedded microfluidic device to study the migration of breast cancer cells显示文摘Recapitulating the tumor microenvironment is a major challenge in the development of in vitro tumor model for the study of cancer biology and therapeutic treatments. 3D multicellular tumor spheroids (MCTS) have been used as reliable models of mimicking in vivo solid tumors. Macrophages and extracellular matrix (ECM), regarded as two key factors of the tumor microenvironment, play significant roles in tumor progression and drug resistance. In order to investigate their effects on tumor cell migration, a microfluidic chip-based 3D breast cancer model was developed by co-culturing monodisperse MCTS with monocytes in 3 D collagen matrix. A reversible bonding technique was employed for the fabrication of the microfluidic chip, which made it easier for MCTS formation and tailoring the MCTS co-culture conditions. When co-culturing monocytes with low invasive T47D spheroids or high invasive MD-MBA-231 spheroids, we found that T47 D cells with the stimulation of macrophage colony-stimulating factor (M-CSF) and MD-MBA-231 cells could polarize monocytes into tumor-associated macrophages (TAMs). The increased stiffness via increasing collagen concentration decreased tumor cell migration, whereas the presence of TAMs enhanced the migration ability of cells.Moreover, M-CSF-activated TAMs promoted the migration of T47 D tumor cells via the regulation of TGFβ1. Overall, this 3D co-culture microfluidic model may be useful for studying tumor progress and may offer a reliable and low-cost method for evaluation of drug efficiency. | Tianying Yuan Dan Gao Shangfu Li Yuyang jiang | 2019 | Chinese Chemical Letters2019，30，2： | 3 |
| 13 | Interaction between insulin-like growth factor binding protein-related protein 1 and transforming growth factor beta 1 in primary hepatic stellate cells显示文摘BACKGROUND:We previously showed that insulin-like growth factor binding protein-related protein 1(IGFBPrP1) is a novel mediator in liver fibrosis.Transforming growth factor beta 1(TGFβ1) is known as the strongest effector of liver fibrosis.Therefore,we aimed to investigate the detailed interaction between IGFBPrP1 and TGFβ1 in primary hepatic stellate cells(HSCs).METHODS:We overexpressed TGFβ1 or IGFBPrP1 and inhibited TGFβ1 expression in primary HSCs for 6,12,24,48,72,and 96 hours to investigate their interaction and observe the accompanying expressions of α-smooth muscle actin(α-SMA),collagen I,fibronectin,and phosphorylated-mothers against decapentaplegic homolog 2/3(p-Smad2/3).RESULTS:We found that the adenovirus vector encoding the TGFβ1 gene(Ad TGFβ1) induced IGFBPrP1 expression while that of α-SMA,collagen I,fibronectin,and TGFβ1 increased gradually.Concomitantly,Ad IGFBPrP1 upregulated TGFβ1,α-SMA,collagen I,fibronectin,and p-Smad2/3 in a time-dependent manner while IGFBPrP1 expression was decreased at 96 hours.Inhibition of TGFβ1 expression reduced the IGFBPrP1-stimulated expression of α-SMA,collagen I,fibronectin,and p-Smad2/3.CONCLUSIONS:These findings for the first time suggest the existence of a possible mutually regulation between IGFBPrP1 and TGFβ1,which likely accelerates liver fibrosis progression.Furthermore,IGFBPrP1 likely participates in liver fibrosis in a TGFβ1-depedent manner,and may act as an upstream regulatory factor of TGFβ1 in the Smad pathway. | Xiu-Qing Li Qian-Qian Zhang Hai-Yan Zhang Xiao-Hong Guo Hui-Qin Fan Li-Xin Liu | 2017 | Hepatobiliary & Pancreatic Diseases International2017，16，4： | 3 |
| 14 | Epithelial defect repair in the auricle and auditory meatus by grafting with cultured adipose-derived mesenchymal stem cell aggregate-extracellular matrix显示文摘Background: Several patients experience persistent otorrhea after a flawless surgical procedure because of insufficient epithelial healing. Several efforts, such as autologous tissue allograft and xenograft, have been made to halt otorrhea. However, a stable technology to induce temporal epithelial repair is yet to be established. Therefore, this study aims to investigate whether implantation of seeding adipose-derived mesenchymal stem cell (ADMSC) aggregates on extracellular matrix (ECM;herein, ADMSC aggregate-ECM) into damaged skin wound promotes skin regeneration. Methods: ADMSC aggregate-ECM was prepared using a previously described procedure that isolated ADMSCs from rabbits and applied to the auricle and auditory meatus wound beds of New Zealand white rabbits. Wound healing was assessed by general observation and hematoxylin and eosin (H&E) staining. Secretion of growth factor of the tissue was evaluated by western blotting. Two other groups, namely, ECM and control, were used. Comparisons of three groups were conducted by one-way analysis of variance analysis. Results: ADMSCs adhered tightly to the ECM and quickly formed cell sheets. At 2 weeks, general observation and H&E staining indicated that the wound healing rates in the ADMSC aggregate-ECM (69.02±6.36%) and ECM (59.32 + 4.10%) groups were higher than that in the control group (43.74± 12.15%;P=0.005, P<0.001, respectively) in ear auricle excisional wounds. At 7 weeks, The scar elevation index was evidently reduced in the ADMSC aggregate-ECM (2.08±0.87) and ECM (2.31 ±0.33) groups compared with the control group (4.06 ±0.45;P < 0.001, P < 0.001, respectively). In addition, the scar elevation index of the ADMSC aggregate-ECM group reached the lowest rate 4 weeks in advance. In auditory meatus excisional wounds, the ADMSC aggregate-ECM group had the largest range of normal skin-like structure at 4 weeks. The ADMSC aggregate-ECM and ECM groups secreted increased amounts of growth factors that contributed to skin regeneration at weeks 1 and 2, respectively. Conclusions: ADMSC aggregate-ECM and ECM are effective repair materials for wound healing, especially ADMSC aggregate- ECM. This approach will provide a meaningful experimental basis for mastoid epithelium repair in subsequent clinical trials. | Wen-Jin Zhang Lei-Guo Ming Jian-Jun Sun | 2019 | Chinese Medical Journal2019，，6： | 3 |
| 15 | 炎症对声带间充质干细胞生物学行为的影响显示文摘目的研究炎症对声带间充质干细胞(vocal fold mesenchymal stem cells,VF-MSCs)生物学行为的影响,为炎症声带损伤修复提供一定的理论依据。方法正常和慢性炎症声带组织分别取自于下咽癌喉全切除的正常声带组织及水肿型声带息肉手术患者切除的标本,所取组织大小约1mm×1mm,每种组织3例,对其行HE、Masson三色染色和Elastin Van Gieson(EVG)染色,观察炎性声带组织较正常组织胶原纤维和弹性纤维改变情况;通过细胞克隆形成实验和MTT细胞生长曲线实验研究炎症对VF-MSCs增殖能力的影响;通过VF-MSCs定向向成骨和成脂细胞分化,研究炎症对VF-MSCs多向分化能力的影响。结果 Masson三色和EVG染色结果显示炎性声带组织固有层细胞外基质(extracellular matrix,ECM)胶原纤维变粗,含量增多,弹力纤维变细,含量减少;细胞克隆形成实验和MTT细胞生长曲线结果显示炎性声带间充质干细胞(inflammatory vocal fold mexenchymal stem cells,I-VF-MSCs)较正常声带间充质干细胞(normal vocal fold mesenchymal stem cells,N-VFMSCs)增殖能力增强;细胞成骨和成脂分化实验结果显示I-VF-MSCs较N-VF-MSCs多向分化能力减弱。结论炎性声带组织较正常声带组织弹性减弱,抗压力增强,炎症促进VF-MSCs增殖能力,抑制VF-MSCs多向分化能力。 | 杨润琴 梁媛媛 邓志宏 | 2014 | 听力学及言语疾病杂志2014，22，3： | 2 |
| 16 | Linking stemness with colorectal cancer initiation, progression, and therapy显示文摘The discovery of cancer stem cells caused a paradigm shift in the concepts of origin and development of colorectal cancer. Several unresolved questions remain in this field though. Are colorectal cancer stem cells the cause or an effect of the disease? How do cancer stem cells assist in colorectal tumor dissemination to distant organs? What are the molecular or environmental factors affecting the roles of these cells in colorectal cancer? Through this review, we investigate the key findings until now and attempt to elucidate the origins, physical properties, microenvironmental niches, as well as the molecular signaling network that support the existence, self-renewal, plasticity, quiescence, and the overall maintenance of cancer stem cells in colorectal cancer. Increasing data show that the cancer stem cells play a crucial role not only in the establishment of the primary colorectal tumor but also in the distant spread of the disease. Hence, we will also look at the mechanisms adopted by cancer stem cells to influence the development of metastasis and evade therapeutic targeting and its role in the overall disease prognosis. Finally, we will illustrate the importance of understanding the biology of these cells to develop improved clinical strategies to tackle colorectal cancer. | Deepak Narayanan Iyer Wai-Yan Sin Lui Ng | 2019 | World Journal of Stem Cells2019，11，8： | 2 |
| 17 | Extracellular matrix and biomimetic engineering microenvironment for neuronal differentiation显示文摘Extracellular matrix(ECM)influences cell differentiation through its structural and biochemical properties.In nervous system,neuronal behavior is influenced by these ECMs structures which are present in a meshwork,fibrous,or tubular forms encompassing specific molecular compositions.In addition to contact guidance,ECM composition and structures also exert its effect on neuronal differentiation.This short report reviewed the native ECM structure and composition in central nervous system and peripheral nervous system,and their impact on neural regeneration and neuronal differentiation.Using topographies,stem cells have been differentiated to neurons.Further,focussing on engineered biomimicking topographies,we highlighted the role of anisotropic topographies in stem cell differentiation to neurons and its recent temporal application for efficient neuronal differentiation. | Deepak Jain Sabrina Mattiassi Eyleen L.Goh Evelyn K.F.Yim | 2020 | Neural Regeneration Research2020，15，4： | 2 |
| 18 | WJSC 6^(th) Anniversary Special Issues(2):Mesenchymal stem cells “Ins” and “Outs” of mesenchymal stem cell osteogenesis in regenerative medicine显示文摘Repair and regeneration of bone requires mesenchymal stem cells that by self-renewal,are able to generate a critical mass of cells with the ability to differentiate into osteoblasts that can produce bone protein matrix(osteoid)and enable its mineralization.The number of human mesenchymal stem cells(hMSCs)diminishes with age and ex vivo replication of hMSCs has limited potential.While propagating hMSCs under hypoxic conditions may maintain their ability to self-renew,the strategy of using human telomerase reverse transcriptase(hTERT)to allow for hMSCs to prolong their replicative lifespan is an attractive means of ensuring a critical mass of cells with the potential to differentiate into various mesodermal structural tissues including bone.However,this strategy must be tempered by the oncogenic potential of TERT-transformed cells,or their ability to enhance already established cancers,the unknown differentiating potential of high population doubling hMSCs and the source of hMSCs(e.g.,bone marrow,adipose-derived,muscle-derived,umbilical cord blood,etc.)that may provide peculiarities to self-renewal,differentiation,and physiologic function that may differ from non-transformed native cells.Tissue engineering approaches to use hMSCs to repair bone defects utilize the growth of hMSCs on three-dimensional scaffolds that can either be a base on which hMSCs can attach and grow or as a means of sequestering growth factors to assist in the chemoattraction and differentiation of native hMSCs.The use of whole native extracellular matrix(ECM)produced by hMSCs,rather than individual ECM components,appear to be advantageous in not only being utilized as a three-dimensional attachment base but also in appropriate orientation of cells and their differentiation through the growth factors that native ECM harbor or in simulating growth factor motifs.The origin of native ECM,whether from hMSCs from young or old individuals is a critical factor in'rejuvenating'hMSCs from older individuals grown on ECM from younger individuals. | Dean T Yamaguchi | 2014 | World Journal of Stem Cells2014，6，2： | 2 |
| 19 | Hyaluronan arrests humanbreast cancer cell growth by prolonging the G0/G1 phase of the cell cycle显示文摘In clinical breast cancer patients,quiescent disseminated tumor cells (DTCs)can persist for a long time in the bone marrow (BM)under the influence of microenvironmental cues.As a high molecular weight polysaccharide,hyaluronan (HA)not only has been shown to regulate cancer processes including cell invasion,metastasis,migration,and proliferation,but also is a major component of the BM extracellular matrix.Here,we tested whether HA promotes breast cancer cell quiescence through detecting cell proliferation,cell cycle phase distribution,and the expression of cell cyclerelated regulator proteins.In our results,HA slowed the growth and prolonged the G0/G1 phase of the highly metastatic,bone-seeking human breast cancer MDA-MB-231BO cell line,which is consistent with results that HA activated p38α/β,inhibited phospho-ERK1/2 levels and reduced the ERK/p38 signaling ratio.Additionally,we examined the crucial cell cycle factors p21^cip1 and Cyclin D1,both of which influence the transition from G1 to S phase.The results revealed that p21^cip1 expression was up-regulated by HA,which was consequently accompanied by a decrease in Cyclin D1 level.Further research with a 3D culture model indicated that HA maintained low Ki-67 and high p21^cip1 expression levels in MDA-MB-231BO cells.In summary,our work revealed that HA might contribute to DTC quiescence. | Xiaoyan Chen Yan Du Yiwen Liu Yiqing He Guoliang Zhang Cuixia Yang Feng Gao | 2018 | Acta Biochimica et Biophysica Sinica2018，50，12： | 2 |
| 20 | Glycosylation of dentin matrix protein 1 is critical for fracture healing via promoting chondrogenesis显示文摘Fractures are frequently occurring diseases that endanger human health. Crucial to fracture healing is cartilage formation, which provides a bone-regeneration environment. Cartilage consists of both chondrocytes and extracellular matrix (ECM). The ECM of cartilage includes collagens and various types of proteoglycans (PGs), which play important roles in maintaining primary stability in fracture healing. The PG form of dentin matrix protein 1 (DMP1-PG) is involved in maintaining the health of articular cartilage and bone. Our previous data have shown that DMP1-PG is richly expressed in the cartilaginous calluses of fracture sites. However, the possible significant role of DMP1-PG in chondrogenesis and fracture healing is unknown. To further detect the potential role of DMP1-PG in fracture repair, we established a mouse fracture model by using a glycosylation site mutant DMP1 mouse (S89G-DMP1 mouse). Upon inspection, fewer cartilaginous calluses and down-regulated expression levels of chondrogenesis genes were observed in the fracture sites of S89G-DMP1 mice. Given the deficiency of DMP1-PG, the impaired IL-6/JAK/STAT signaling pathway was observed to affect the chondrogenesis of fracture healing. Overall, these results suggest that DMP1-PG is an indispensable proteoglycan in chondrogenesis during fracture healing. | Hui Xue Dike Tao Yuteng Weng Qiqi Fan Shuang Zhou Ruilin Zhang Han Zhang Rui Yue Xiaogang Wang Zuolin Wang Yao Sun | 2019 | Frontiers of Medicine2019，13，5： | 2 |
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