Background The two most basic properties of mesenchymal stem cells （MSCs） are the capacities to selfrenew indefinitely and differentiate into multiple cells and tissue types. The cells from human umbilical cord Whar...Background The two most basic properties of mesenchymal stem cells （MSCs） are the capacities to selfrenew indefinitely and differentiate into multiple cells and tissue types. The cells from human umbilical cord Wharton＇ s Jelly have properties of MSCs and represent a rich source of primitive cells. This study was conducted to explore the possibility of inducing human umbilical cord Wharton＇ s Jelly-derived MSCs to differentiate into nerve-like cells.Methods MSCs were cultured from the Wharton＇ s Jelly taken from human umbilical cord of babies delivered after full-term normal labor. Salvia miltiorrhiza and [3-mercaptoethanol were used to induce the human umbilical cord-derived MSCs to differentiate The expression of neural protein markers was shown by immunocytochemistry. The induction process was monitored by phase contrast microscopy, electron microscopy （EM）, and laser scanning confocal microscopy （LSCM） . The pleiotrophin and nestin genes were measured by reverse transcription-polymerase chain reaction （RT-PCR）.Results MSCs in the Wharton＇ s Jelly were easily attainable and could be maintained and expanded in culture. They were positive for markers of MSCs, but negative for markers of hematopoietic cells and graft-versus-host disease （GVHD）-related cells. Treatment with Salvia mihiorrhiza caused Wharton＇ s Jelly cells to undergo profound morphological changes. The induced MSCs developed rounded cell bodies with multiple neurite-like extensions. Eventually they developed processes that formed networks reminiscent of primary cultures of neurons. Salvia mihiorrhiza and β-mercaptoethanol also induced MSCs to express nestin, β-tubulin Ⅲ, neurofilament （NF） and glial fibrillary acidic protein （GFAP）. It was confirmed by RT-PCR that MSCs could express pleiotrophin both before and after induction by Salvia miltiorrhiza. The expression was markedly enhanced after induction and the nestin gene was also expressed.Conclusions MSCs could be isolated from human umbilical cord Wharto展开更多
The Third Universal Definition of Myocardial Infarction(MI) requires cardiac myocyte necrosis with an increase and/or a decrease in a patient's plasma of cardiac troponin(cT n) with at least one cT n measurement g...The Third Universal Definition of Myocardial Infarction(MI) requires cardiac myocyte necrosis with an increase and/or a decrease in a patient's plasma of cardiac troponin(cT n) with at least one cT n measurement greater than the 99 th percentile of the upper normal reference limit during:(1) symptoms of myocardialischemia;(2) new significant electrocardiogram(ECG) ST-segment/T-wave changes or left bundle branch block;(3) the development of pathological ECG Q waves;(4) new loss of viable myocardium or regional wall motion abnormality identified by an imaging procedure; or(5) identification of intracoronary thrombus by angiography or autopsy.Myocardial infarction,when diagnosed,is now classified into five types.Detection of a rise and a fall of troponin are essential to the diagnosis of acute MI.However,high sensitivity troponin assays can increase the sensitivity but decrease the specificity of MI diagnosis.The ECG remains a cornerstone in the diagnosis of MI and should be frequently repeated,especially if the initial ECG is not diagnostic of MI.There have been significant advances in adjunctive pharmacotherapy,procedural techniques and stent technology in the treatment of patients with MIs.The routine use of antiplatelet agents such as clopidogrel,prasugrel or ticagrelor,in addition to aspirin,reduces patient morbidity and mortality.Percutaneous coronary intervention(PCI) in a timely manner is the primary treatment of patients with acute ST segment elevation MI.Drug eluting coronary stents are safe and beneficial with primary coronary intervention.Treatment with direct thrombin inhibitors during PCI is non-inferior to unfractionated heparin and glycoprotein Ⅱb/Ⅲa receptor antagonists and is associated with a significant reduction in bleeding.The intra-coronary use of a glycoprotein Ⅱb/Ⅲa antagonist can reduce infarct size.Pre- and post-conditioning techniques can provide additional cardioprotection.However,the incidence and mortality due to MI continues to be high despite all these recent advances.The ini展开更多
It is estimated that 20000 to 30000 new patients are diagnosed with osteonecrosis annually accounting for approximately 10% of the 250000 total hip arthroplasties done annually in the United States. Thelack of level 1...It is estimated that 20000 to 30000 new patients are diagnosed with osteonecrosis annually accounting for approximately 10% of the 250000 total hip arthroplasties done annually in the United States. Thelack of level 1 evidence in the literature makes it difficult to identify optimal treatment protocols to manage patients with pre-collapse avascular necrosis of the femoral head, and early intervention prior to collapse is critical to successful outcomes in joint preserving procedures. There have been a variety of traumatic and atraumatic factors that have been identified as risk factors for osteonecrosis, but the etiology and pathogenesis still remains unclear. Current osteonecrosis diagnosis is dependent upon plain anteroposterior and frog-leg lateral radiographs of the hip, followed by magnetic resonance imaging(MRI). Generally, the first radiographic changes seen by radiograph will be cystic and sclerotic changes in the femoral head. Although the diagnosis may be made by radiograph, plain radiographs are generally insufficient for early diagnosis, therefore MRI is considered the most accurate benchmark. Treatment options include pharmacologic agents such as bisphosphonates and statins, biophysical treatments, as well as joint-preserving and joint-replacing surgeries. the surgical treatment of osteonecrosis of the femoral head can be divided into two major branches: femoral head sparing procedures(FHSP) and femoral head replacement procedures(FHRP). In general, FHSP are indicated at pre-collapse stages with minimal symptoms whereas FHRP are preferred at post-collapse symptomatic stages. It is difficult to know whether any treatment modality changes the natural history of core decompression since the true natural history of core decompression has not been delineated.展开更多
The importance of cancer stem cells （CSCs） in tumor-initiation has been firmly established in leukemia and recently reported for a variety of solid tumors. However, the role of CSCs in multistage cancer progression,...The importance of cancer stem cells （CSCs） in tumor-initiation has been firmly established in leukemia and recently reported for a variety of solid tumors. However, the role of CSCs in multistage cancer progression, particularly with respect to metastasis, has not been well-defined. Cancer metastasis requires the seeding and successful colonization of specialized CSCs at distant organs. The biology of normal stem cells and CSCs share remarkable similarities and may have important implications when applied to the study of cancer metastasis. Furthermore, overlapping sets of molecules and pathways have recently been identified to regulate both stem cell migration and cancer metastasis. These molecules constitute a complex network of cellular interactions that facilitate both the initiation of the pre-metastasis niche by the primary tumor and the formation of a nurturing organ microenvironment for migrating CSCs. In this review, we surveyed the recent advances in this dynamic field and propose a unified model of cancer progression in which CSCs assume a central role in both tumorigenesis and metastasis. Better understanding of CSCs as a fundamental component of the metastatic cascade will lead to novel therapeutic strategies against metastatic cancer.展开更多
The cell-biological program termed the epithelial-to-mesenchymal transition （EMT） plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circui...The cell-biological program termed the epithelial-to-mesenchymal transition （EMT） plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circuits of a particular cell, this program can drive fully epithelial cells to enter into a series of phenotypic states arrayed along the epithelial-mesenehymal phenotypic axis. These cell states display distinctive cellular characteristics, including stemness, invasiveness, drug-resistance and the ability to form metastases at distant organs, and thereby contribute to cancer metastasis and relapse. Currently we still lack a coherent overview of the molecular and biochemical mechanisms inducing cells to enter various states along the epithelial-mesenchymal phenotypic spectrum. An improved understanding of the dynamic and plastic nature of the EMT program has the potential to yield novel therapies targeting this cellular program that may aid in the management of high-grade malignancies.展开更多
Human pluripotent stem cells represent a potentially unlimited source of functional pancreatic endocrine lineage cells. Here we report a highly efficient approach to induce human embryonic stem （ES） cells and induce...Human pluripotent stem cells represent a potentially unlimited source of functional pancreatic endocrine lineage cells. Here we report a highly efficient approach to induce human embryonic stem （ES） cells and induced pluripo- tent stem （iPS） cells to differentiate into mature insulin-producing cells in a chemical-defined culture system. The differentiated human ES cells obtained by this approach comprised nearly 25% insulin-positive cells as assayed by flow cytometry analysis, which released insulin/C-peptide in response to glucose stimuli in a manner comparable to that of adult human islets. Most of these insulin-producing cells co-expressed mature β cell-specific markers such as NKX6-1 and PDX1, indicating a similar gene expression pattern to adult islet β cells in vivo. In this study, we also demonstrated that EGF facilitates the expansion of PDXl-positive pancreatic progenitors. Moreover, our protocol also succeeded in efficiently inducing human iPS cells to differentiate into insuIin-producing ceils. Therefore, this work not only provides a new model to study the mechanism of human pancreatic specialization and maturation in vitro, but also enhances the possibility of utilizing patient-specific iPS cells for the treatment of diabetes.展开更多
"科学、技术、工程与数学"(Science,Technology,Engineering and Mathematics,简称STEM)教育是由美国发起、主导并正在兴盛于世界各国的一场教育运动。它的提出,主要因应于国际竞争、社会高科技的发展等对人才的需求。这决定..."科学、技术、工程与数学"(Science,Technology,Engineering and Mathematics,简称STEM)教育是由美国发起、主导并正在兴盛于世界各国的一场教育运动。它的提出,主要因应于国际竞争、社会高科技的发展等对人才的需求。这决定了其功利主义特点。因此,当我们思考STEM的教育价值时,必须将其功利主义框架转化为知识创造框架,追寻STEM的知识价值和教育内在价值。在此意义上,先于STEM而产生的科学、技术与社会(Science,Technology and Society,简称STS)教育,更具学术的背景和基础,可以作为改造STEM教育的合理框架。此外,我们还应深入探究STEM各相关学科自身的价值,并在此基础上寻求它们之间相互融合的价值和可能。展开更多
To solve the problem of immune incompatibility, nuclear transplantation has been envisaged as a means to produce cells or tissues for human autologous transplantation. Here we have derived embryonic stem cells by the ...To solve the problem of immune incompatibility, nuclear transplantation has been envisaged as a means to produce cells or tissues for human autologous transplantation. Here we have derived embryonic stem cells by the transfer of human somatic nuclei into rabbit oocytes. The number of blastocysts that developed from the fused nuclear transfer was comparable among nuclear donors at ages of 5, 42, 52 and 60 years, and nuclear transfer (NT) embryonic stem cells (ntES cells) were subsequently derived from each of the four age groups. These results suggest that human somatic nuclei can form ntES cells independent of the age of the donor. The derived ntES cells are human based on karyotype, isogenicity, in situ hybridization, PCR and immunocytochemistry with probes that distinguish between the various species. The ntES cells maintain the capability of sustained growth in an undifferentiated state, and form embryoid bodies, which, on further induction, give rise to cell types such as neuron and muscle, as well as mixed cell populations that express markers representative of all three germ layers. Thus, ntES cells derived from human somatic cells by NT to rabbit eggs retain phenotypes similar to those of conventional human ES cells, including the ability to undergo multilineage cellular differentiation.展开更多
Background The infarct size determines the long-term prognosis of patients with acute myocardial infarction (AMI). There is a growing interest in repairing scar area by transplanting bone marrow stem cells. However, ...Background The infarct size determines the long-term prognosis of patients with acute myocardial infarction (AMI). There is a growing interest in repairing scar area by transplanting bone marrow stem cells. However, effectiveness of intracoronary injection of bone marrow mesenchymal stem cells (BMSCs) in patients with AMI still remains unclear.Methods Sixty-nine patients with AMI after percutaneous coronary intervention (PCI) were randomly divided into intracoronary injection of BMSCs (n=34) and saline (control group, n=35) groups. Serial single positron emission computer tomography (SPECT), cardiac echo and cardiac electromechanical mapping were done at the designed time intervals until six months after transplantation of BMSCs or injection of saline. Results The proportion with functional defect decreased significantly in the BMSCs patients after three months [(13±5)%] compared with that pre-transplantation [(32±11)%] and the control group [(28±10)%] at three month follow-up (P<0.05, respectively). Wall movement velocity over the infracted region increased significantly in the BMSCs group [(4.2±2.5) cm/s vs (2.2±1.3) cm/s, P<0.05], but not in the control group [(2.2±1.5) cm/s vs (2.7±1.7) cm/s, P>0.05]. Left ventricular ejection fraction (LVEF) three months after transplantation in BMSCs group increased significantly compared with that pre-implantation and with that of the control group at three months post-injection [(67±11)% vs (49±9)% and (53±8)%, P<0.05 respectively]. SPECT scan results showed that perfusion defect was improved significantly in BMSCs group at three-month follow-up compared with that in the control group [(134±66)cm2 vs (185±87)cm2, P<0.01]. At the same time, left ventricular end-diastolic volume [(136±31) ml vs (162±27) ml, P<0.05] and end-systolic volume [(63±20) ml vs (88±19) ml, P<0.05] decreased synchronously. The ratio of end-systolic pressure to end-systolic volume [P_ syst/ESV, (2.84±1.30) mmHg/ml vs (1.72±1.23) mmHg/ml, P<0.05] increased significantly. Cardiac展开更多
AIM: Recent reports have shown the capacity of mesenchymal stem cells (MSCs) to differentiate into hepatocytes in vitro and in vivo. MSCs administration could repair injured liver, lung, or heart through reducing infl...AIM: Recent reports have shown the capacity of mesenchymal stem cells (MSCs) to differentiate into hepatocytes in vitro and in vivo. MSCs administration could repair injured liver, lung, or heart through reducing inflammation, collagen deposition, and remodeling. These results provide a clue to treatment of liver fibrosis. The aim of this study was to investigate the effect of infusion of bone marrow (BM)-derived MSCs on the experimental liver fibrosis in rats. METHODS: MSCs isolated from BM in male Fischer 344 rats were infused to female Wistar rats induced with carbon tetrachloride (CCI4) or dimethylnitrosamine (DMN). There were two random groups on the 42nd d of CCI4: CCl4/MSCs, to infuse a dose of MSCs alone; CCI4/saline, to infuse the same volume of saline as control. There were another three random groups after exposure to DMN: DMN10/MSCs, to infuse the same dose of MSCs on d 10; DMN10/saline, to infuse the same volume of saline on d 10; DMN20/MSCs, to infuse the same dose of MSCs on d 20. The morphological and behavioral changes of rats were monitored everyday. After 4-6 wk of MSCs administration, all rats were killed and fibrosis index were assessed by histopathology and radioimmunoassay. Smooth muscle alpha-actin (alpha-SMA) of liver were tested by immunohistochemistry and quantified by IBAS 2.5 software. Male rats sex determination region on the Y chromosome (sry) gene were explored by PCR. RESULTS: Compared to controls, infusion of MSCs reduced the mortality rates of incidence in CCl4-induced model (10% vs 20%) and in DMN-induced model (20-40% vs 90%).The amount of collagen deposition and alpha-SMA staining was about 40-50% lower in liver of rats with MSCs than that of rats without MSCs. The similar results were observed in fibrosis index. And the effect of the inhibition of fibrogenesis was greater in DMN10/MSCs than in DMN20/MSCs. The sry gene was positive in the liver of rats with MSCs treatment by PCR. CONCLUSION: MSCs treatment can protect against experimental liver fibrosis in CCMnduced or DMN-in展开更多
BACKGROUND: Cancer of the pancreas is the fourth leading cause of cancer death in industrialized countries. In malignancy, actively proliferating cells may be effectively targeted and killed by anti-cancer therapies, ...BACKGROUND: Cancer of the pancreas is the fourth leading cause of cancer death in industrialized countries. In malignancy, actively proliferating cells may be effectively targeted and killed by anti-cancer therapies, but stem cells may survive and support re-growth of the tumor. Thus, new strategies for the treatment of cancer clearly will also have to target cancer stem cells. The goal of the present study was to determine whether pancreatic carcinoma cell growth may be driven by a subpopulation of cancer stem cells. Because previous data implicated ABCG2 and CD133 as stem cell markers in hematopoietic and neural stem/progenitor cells, we analyzed the expression of these two proteins in pancreatic carcinoma cell lines. METHODS: Five established pancreatic adenocarcinoma cell lines were analyzed. Total RNA was isolated and real- time RT-PCR was performed to determine the expression of ABCG2 and CD133. Surface expression of ABCG2 and CD133 was analyzed by flow cytometric analysis. RESULTS: All pancreatic carcinoma cell lines tested expressed significantly higher levels of ABCG2 than non-malignant fibroblasts or two other malignant non- pancreatic cell lines, i.e., SaOS2 osteosarcoma and SKOV3 ovarian cancer. Elevated CD133 expression was found in two out of five pancreatic carcinoma cell lines tested. Using flow cytometric analysis we confirmed surface expression of ABCG2 in all five lines. Yet, CD133 surface expression was detectable in the two cell lines, A818-6 and PancTu1, which exhibited higher mRNA levels.CONCLUSIONS: Two stem cell markers, ABCG2 and CD133 are expressed in pancreatic carcinoma cell lines. ABCG2 and/or CD133 positive cells may represent subpopulation of putative cancer stem cells also in this malignancy. Because cancer stem cells are thought to be responsible for tumor initiation and its recurrence after an initial response to chemotherapy, they may be a very promising target for new drug developments.展开更多
AIM: To evaluate safety and feasibility of autologous bone marrow-enriched CD34+ hematopoietic stem cell Tx through the hepatic artery in patients with decompensated cirrhosis.METHODS: Four patients with decompensated...AIM: To evaluate safety and feasibility of autologous bone marrow-enriched CD34+ hematopoietic stem cell Tx through the hepatic artery in patients with decompensated cirrhosis.METHODS: Four patients with decompensated cirrhosis were included. Approximately 200 mL of the bone marrow of the patients was aspirated, and CD34+ stem cells were selected. Between 3 to 10 million CD34+ cells were isolated. The cells were slowly infused through the hepatic artery of the patients.RESULTS: Patient 1 showed marginal improvement in serum albumin and no significant changes in other test results. In patient 2 prothrombin time was decreased; however, her total bilirubin, serum creatinine, and Model of End-Stage Liver Disease (MELD) score worsened at the end of follow up. In patient 3 there was improvement in serum albumin, porthrombin time (PT), and MELD score. Patient 4 developed radiocontrast nephropathy after the procedure, and progressed to type 1 hepatorenal syndrome and died of liver failure a few days later. Because of the major side effects seen in the last patient, the trial was prematurely stopped.CONCLUSION: Infusion of CD34+ stem cells through the hepatic artery is not safe in decompensated cirrhosis. Radiocontrast nephropathy and hepatorenal syndrome could be major side effects. However, this study doesnot preclude infusion of CD34+ stem cells through other routes.展开更多
Wnt signaling transduces evolutionarily conserved pathways which play important roles in initiating and regulating a diverse range of cellular activities,including cell proliferation,calcium homeostasis,and cell polar...Wnt signaling transduces evolutionarily conserved pathways which play important roles in initiating and regulating a diverse range of cellular activities,including cell proliferation,calcium homeostasis,and cell polarity.The role of Wnt signaling in controlling cell proliferation and stem cell self-renewal is primarily carried out through the canonical pathway,which is the best-characterized the multiple Wnt signaling branches.The past 10 years has seen a rapid expansion in our understanding of the complexity of this pathway,as many new components of Wnt signaling have been identified and linked to signaling regulation,stem cell functions,and adult tissue homeostasis.Additionally,a substantial body of evidence links Wnt signaling to tumorigenesis of cancer types and implicates it in the development of cancer drug resistance.Thus,a better understanding of the mechanisms by which dysregulation of Wnt signaling precedes the development and progression of human cancer may hasten the development of pathway inhibitors to augment current therapy.This review summarizes and synthesizes our current knowledge of the canonical Wnt pathway in development and disease.We begin with an overview of the components of the canonical Wnt signaling pathway and delve into the role this pathway has been shown to play in stemness,tumorigenesis,and cancer drug resistance.Ultimately,we hope to present an organized collection of evidence implicating Wnt signaling in tumorigenesis and chemoresistance to facilitate the pursuit of Wnt pathway modulators that may improve outcomes of cancers in which Wnt signaling contributes to aggressive disease and/or treatment resistance.展开更多
文摘Background The two most basic properties of mesenchymal stem cells （MSCs） are the capacities to selfrenew indefinitely and differentiate into multiple cells and tissue types. The cells from human umbilical cord Wharton＇ s Jelly have properties of MSCs and represent a rich source of primitive cells. This study was conducted to explore the possibility of inducing human umbilical cord Wharton＇ s Jelly-derived MSCs to differentiate into nerve-like cells.Methods MSCs were cultured from the Wharton＇ s Jelly taken from human umbilical cord of babies delivered after full-term normal labor. Salvia miltiorrhiza and [3-mercaptoethanol were used to induce the human umbilical cord-derived MSCs to differentiate The expression of neural protein markers was shown by immunocytochemistry. The induction process was monitored by phase contrast microscopy, electron microscopy （EM）, and laser scanning confocal microscopy （LSCM） . The pleiotrophin and nestin genes were measured by reverse transcription-polymerase chain reaction （RT-PCR）.Results MSCs in the Wharton＇ s Jelly were easily attainable and could be maintained and expanded in culture. They were positive for markers of MSCs, but negative for markers of hematopoietic cells and graft-versus-host disease （GVHD）-related cells. Treatment with Salvia mihiorrhiza caused Wharton＇ s Jelly cells to undergo profound morphological changes. The induced MSCs developed rounded cell bodies with multiple neurite-like extensions. Eventually they developed processes that formed networks reminiscent of primary cultures of neurons. Salvia mihiorrhiza and β-mercaptoethanol also induced MSCs to express nestin, β-tubulin Ⅲ, neurofilament （NF） and glial fibrillary acidic protein （GFAP）. It was confirmed by RT-PCR that MSCs could express pleiotrophin both before and after induction by Salvia miltiorrhiza. The expression was markedly enhanced after induction and the nestin gene was also expressed.Conclusions MSCs could be isolated from human umbilical cord Wharto
基金Supported by Research facilities at the James A Haley VA Hospitalin part+3 种基金Grants from the Florida King Biomedical Research Programthe Muscular Dystrophy Associationthe Robert O Law Foundationthe Cornelius Foundation
文摘The Third Universal Definition of Myocardial Infarction(MI) requires cardiac myocyte necrosis with an increase and/or a decrease in a patient's plasma of cardiac troponin(cT n) with at least one cT n measurement greater than the 99 th percentile of the upper normal reference limit during:(1) symptoms of myocardialischemia;(2) new significant electrocardiogram(ECG) ST-segment/T-wave changes or left bundle branch block;(3) the development of pathological ECG Q waves;(4) new loss of viable myocardium or regional wall motion abnormality identified by an imaging procedure; or(5) identification of intracoronary thrombus by angiography or autopsy.Myocardial infarction,when diagnosed,is now classified into five types.Detection of a rise and a fall of troponin are essential to the diagnosis of acute MI.However,high sensitivity troponin assays can increase the sensitivity but decrease the specificity of MI diagnosis.The ECG remains a cornerstone in the diagnosis of MI and should be frequently repeated,especially if the initial ECG is not diagnostic of MI.There have been significant advances in adjunctive pharmacotherapy,procedural techniques and stent technology in the treatment of patients with MIs.The routine use of antiplatelet agents such as clopidogrel,prasugrel or ticagrelor,in addition to aspirin,reduces patient morbidity and mortality.Percutaneous coronary intervention(PCI) in a timely manner is the primary treatment of patients with acute ST segment elevation MI.Drug eluting coronary stents are safe and beneficial with primary coronary intervention.Treatment with direct thrombin inhibitors during PCI is non-inferior to unfractionated heparin and glycoprotein Ⅱb/Ⅲa receptor antagonists and is associated with a significant reduction in bleeding.The intra-coronary use of a glycoprotein Ⅱb/Ⅲa antagonist can reduce infarct size.Pre- and post-conditioning techniques can provide additional cardioprotection.However,the incidence and mortality due to MI continues to be high despite all these recent advances.The ini
文摘It is estimated that 20000 to 30000 new patients are diagnosed with osteonecrosis annually accounting for approximately 10% of the 250000 total hip arthroplasties done annually in the United States. Thelack of level 1 evidence in the literature makes it difficult to identify optimal treatment protocols to manage patients with pre-collapse avascular necrosis of the femoral head, and early intervention prior to collapse is critical to successful outcomes in joint preserving procedures. There have been a variety of traumatic and atraumatic factors that have been identified as risk factors for osteonecrosis, but the etiology and pathogenesis still remains unclear. Current osteonecrosis diagnosis is dependent upon plain anteroposterior and frog-leg lateral radiographs of the hip, followed by magnetic resonance imaging(MRI). Generally, the first radiographic changes seen by radiograph will be cystic and sclerotic changes in the femoral head. Although the diagnosis may be made by radiograph, plain radiographs are generally insufficient for early diagnosis, therefore MRI is considered the most accurate benchmark. Treatment options include pharmacologic agents such as bisphosphonates and statins, biophysical treatments, as well as joint-preserving and joint-replacing surgeries. the surgical treatment of osteonecrosis of the femoral head can be divided into two major branches: femoral head sparing procedures(FHSP) and femoral head replacement procedures(FHRP). In general, FHSP are indicated at pre-collapse stages with minimal symptoms whereas FHRP are preferred at post-collapse symptomatic stages. It is difficult to know whether any treatment modality changes the natural history of core decompression since the true natural history of core decompression has not been delineated.
文摘The importance of cancer stem cells （CSCs） in tumor-initiation has been firmly established in leukemia and recently reported for a variety of solid tumors. However, the role of CSCs in multistage cancer progression, particularly with respect to metastasis, has not been well-defined. Cancer metastasis requires the seeding and successful colonization of specialized CSCs at distant organs. The biology of normal stem cells and CSCs share remarkable similarities and may have important implications when applied to the study of cancer metastasis. Furthermore, overlapping sets of molecules and pathways have recently been identified to regulate both stem cell migration and cancer metastasis. These molecules constitute a complex network of cellular interactions that facilitate both the initiation of the pre-metastasis niche by the primary tumor and the formation of a nurturing organ microenvironment for migrating CSCs. In this review, we surveyed the recent advances in this dynamic field and propose a unified model of cancer progression in which CSCs assume a central role in both tumorigenesis and metastasis. Better understanding of CSCs as a fundamental component of the metastatic cascade will lead to novel therapeutic strategies against metastatic cancer.
文摘The cell-biological program termed the epithelial-to-mesenchymal transition （EMT） plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circuits of a particular cell, this program can drive fully epithelial cells to enter into a series of phenotypic states arrayed along the epithelial-mesenehymal phenotypic axis. These cell states display distinctive cellular characteristics, including stemness, invasiveness, drug-resistance and the ability to form metastases at distant organs, and thereby contribute to cancer metastasis and relapse. Currently we still lack a coherent overview of the molecular and biochemical mechanisms inducing cells to enter various states along the epithelial-mesenchymal phenotypic spectrum. An improved understanding of the dynamic and plastic nature of the EMT program has the potential to yield novel therapies targeting this cellular program that may aid in the management of high-grade malignancies.
文摘Human pluripotent stem cells represent a potentially unlimited source of functional pancreatic endocrine lineage cells. Here we report a highly efficient approach to induce human embryonic stem （ES） cells and induced pluripo- tent stem （iPS） cells to differentiate into mature insulin-producing cells in a chemical-defined culture system. The differentiated human ES cells obtained by this approach comprised nearly 25% insulin-positive cells as assayed by flow cytometry analysis, which released insulin/C-peptide in response to glucose stimuli in a manner comparable to that of adult human islets. Most of these insulin-producing cells co-expressed mature β cell-specific markers such as NKX6-1 and PDX1, indicating a similar gene expression pattern to adult islet β cells in vivo. In this study, we also demonstrated that EGF facilitates the expansion of PDXl-positive pancreatic progenitors. Moreover, our protocol also succeeded in efficiently inducing human iPS cells to differentiate into insuIin-producing ceils. Therefore, this work not only provides a new model to study the mechanism of human pancreatic specialization and maturation in vitro, but also enhances the possibility of utilizing patient-specific iPS cells for the treatment of diabetes.
文摘"科学、技术、工程与数学"(Science,Technology,Engineering and Mathematics,简称STEM)教育是由美国发起、主导并正在兴盛于世界各国的一场教育运动。它的提出,主要因应于国际竞争、社会高科技的发展等对人才的需求。这决定了其功利主义特点。因此,当我们思考STEM的教育价值时,必须将其功利主义框架转化为知识创造框架,追寻STEM的知识价值和教育内在价值。在此意义上,先于STEM而产生的科学、技术与社会(Science,Technology and Society,简称STS)教育,更具学术的背景和基础,可以作为改造STEM教育的合理框架。此外,我们还应深入探究STEM各相关学科自身的价值,并在此基础上寻求它们之间相互融合的价值和可能。
基金supported by grants from the Major State Basic Research Development Program of China(No.001CB5099)the National High Technology Research and Development Program of China(No.2001AA216121)+3 种基金National Natural Science Foundation of China(No.30040003)Projects of Shanghai Science&Technology Development Foundation(No.99DJ14002,00DJ14033,01DJ14003)the Chinese Academy of Sciences(No.KSCX-2-3-08)Shanghai Municipal Education Commission and by Shanghai Second Medical University
文摘To solve the problem of immune incompatibility, nuclear transplantation has been envisaged as a means to produce cells or tissues for human autologous transplantation. Here we have derived embryonic stem cells by the transfer of human somatic nuclei into rabbit oocytes. The number of blastocysts that developed from the fused nuclear transfer was comparable among nuclear donors at ages of 5, 42, 52 and 60 years, and nuclear transfer (NT) embryonic stem cells (ntES cells) were subsequently derived from each of the four age groups. These results suggest that human somatic nuclei can form ntES cells independent of the age of the donor. The derived ntES cells are human based on karyotype, isogenicity, in situ hybridization, PCR and immunocytochemistry with probes that distinguish between the various species. The ntES cells maintain the capability of sustained growth in an undifferentiated state, and form embryoid bodies, which, on further induction, give rise to cell types such as neuron and muscle, as well as mixed cell populations that express markers representative of all three germ layers. Thus, ntES cells derived from human somatic cells by NT to rabbit eggs retain phenotypes similar to those of conventional human ES cells, including the ability to undergo multilineage cellular differentiation.
文摘Background The infarct size determines the long-term prognosis of patients with acute myocardial infarction (AMI). There is a growing interest in repairing scar area by transplanting bone marrow stem cells. However, effectiveness of intracoronary injection of bone marrow mesenchymal stem cells (BMSCs) in patients with AMI still remains unclear.Methods Sixty-nine patients with AMI after percutaneous coronary intervention (PCI) were randomly divided into intracoronary injection of BMSCs (n=34) and saline (control group, n=35) groups. Serial single positron emission computer tomography (SPECT), cardiac echo and cardiac electromechanical mapping were done at the designed time intervals until six months after transplantation of BMSCs or injection of saline. Results The proportion with functional defect decreased significantly in the BMSCs patients after three months [(13±5)%] compared with that pre-transplantation [(32±11)%] and the control group [(28±10)%] at three month follow-up (P<0.05, respectively). Wall movement velocity over the infracted region increased significantly in the BMSCs group [(4.2±2.5) cm/s vs (2.2±1.3) cm/s, P<0.05], but not in the control group [(2.2±1.5) cm/s vs (2.7±1.7) cm/s, P>0.05]. Left ventricular ejection fraction (LVEF) three months after transplantation in BMSCs group increased significantly compared with that pre-implantation and with that of the control group at three months post-injection [(67±11)% vs (49±9)% and (53±8)%, P<0.05 respectively]. SPECT scan results showed that perfusion defect was improved significantly in BMSCs group at three-month follow-up compared with that in the control group [(134±66)cm2 vs (185±87)cm2, P<0.01]. At the same time, left ventricular end-diastolic volume [(136±31) ml vs (162±27) ml, P<0.05] and end-systolic volume [(63±20) ml vs (88±19) ml, P<0.05] decreased synchronously. The ratio of end-systolic pressure to end-systolic volume [P_ syst/ESV, (2.84±1.30) mmHg/ml vs (1.72±1.23) mmHg/ml, P<0.05] increased significantly. Cardiac
基金Supported by the Major State Basic Research Development Program of China (973 Program),No. 2001CB509904 the Key Scientific and Technological Projects of Guangdong Province, No. 2003A3020103+1 种基金the Key Scientific and Technological Projects of Guangzhou City, No. 2002U13E0011the National Natural Science Foundation of China, No. 30100188
文摘AIM: Recent reports have shown the capacity of mesenchymal stem cells (MSCs) to differentiate into hepatocytes in vitro and in vivo. MSCs administration could repair injured liver, lung, or heart through reducing inflammation, collagen deposition, and remodeling. These results provide a clue to treatment of liver fibrosis. The aim of this study was to investigate the effect of infusion of bone marrow (BM)-derived MSCs on the experimental liver fibrosis in rats. METHODS: MSCs isolated from BM in male Fischer 344 rats were infused to female Wistar rats induced with carbon tetrachloride (CCI4) or dimethylnitrosamine (DMN). There were two random groups on the 42nd d of CCI4: CCl4/MSCs, to infuse a dose of MSCs alone; CCI4/saline, to infuse the same volume of saline as control. There were another three random groups after exposure to DMN: DMN10/MSCs, to infuse the same dose of MSCs on d 10; DMN10/saline, to infuse the same volume of saline on d 10; DMN20/MSCs, to infuse the same dose of MSCs on d 20. The morphological and behavioral changes of rats were monitored everyday. After 4-6 wk of MSCs administration, all rats were killed and fibrosis index were assessed by histopathology and radioimmunoassay. Smooth muscle alpha-actin (alpha-SMA) of liver were tested by immunohistochemistry and quantified by IBAS 2.5 software. Male rats sex determination region on the Y chromosome (sry) gene were explored by PCR. RESULTS: Compared to controls, infusion of MSCs reduced the mortality rates of incidence in CCl4-induced model (10% vs 20%) and in DMN-induced model (20-40% vs 90%).The amount of collagen deposition and alpha-SMA staining was about 40-50% lower in liver of rats with MSCs than that of rats without MSCs. The similar results were observed in fibrosis index. And the effect of the inhibition of fibrogenesis was greater in DMN10/MSCs than in DMN20/MSCs. The sry gene was positive in the liver of rats with MSCs treatment by PCR. CONCLUSION: MSCs treatment can protect against experimental liver fibrosis in CCMnduced or DMN-in
文摘BACKGROUND: Cancer of the pancreas is the fourth leading cause of cancer death in industrialized countries. In malignancy, actively proliferating cells may be effectively targeted and killed by anti-cancer therapies, but stem cells may survive and support re-growth of the tumor. Thus, new strategies for the treatment of cancer clearly will also have to target cancer stem cells. The goal of the present study was to determine whether pancreatic carcinoma cell growth may be driven by a subpopulation of cancer stem cells. Because previous data implicated ABCG2 and CD133 as stem cell markers in hematopoietic and neural stem/progenitor cells, we analyzed the expression of these two proteins in pancreatic carcinoma cell lines. METHODS: Five established pancreatic adenocarcinoma cell lines were analyzed. Total RNA was isolated and real- time RT-PCR was performed to determine the expression of ABCG2 and CD133. Surface expression of ABCG2 and CD133 was analyzed by flow cytometric analysis. RESULTS: All pancreatic carcinoma cell lines tested expressed significantly higher levels of ABCG2 than non-malignant fibroblasts or two other malignant non- pancreatic cell lines, i.e., SaOS2 osteosarcoma and SKOV3 ovarian cancer. Elevated CD133 expression was found in two out of five pancreatic carcinoma cell lines tested. Using flow cytometric analysis we confirmed surface expression of ABCG2 in all five lines. Yet, CD133 surface expression was detectable in the two cell lines, A818-6 and PancTu1, which exhibited higher mRNA levels.CONCLUSIONS: Two stem cell markers, ABCG2 and CD133 are expressed in pancreatic carcinoma cell lines. ABCG2 and/or CD133 positive cells may represent subpopulation of putative cancer stem cells also in this malignancy. Because cancer stem cells are thought to be responsible for tumor initiation and its recurrence after an initial response to chemotherapy, they may be a very promising target for new drug developments.
文摘AIM: To evaluate safety and feasibility of autologous bone marrow-enriched CD34+ hematopoietic stem cell Tx through the hepatic artery in patients with decompensated cirrhosis.METHODS: Four patients with decompensated cirrhosis were included. Approximately 200 mL of the bone marrow of the patients was aspirated, and CD34+ stem cells were selected. Between 3 to 10 million CD34+ cells were isolated. The cells were slowly infused through the hepatic artery of the patients.RESULTS: Patient 1 showed marginal improvement in serum albumin and no significant changes in other test results. In patient 2 prothrombin time was decreased; however, her total bilirubin, serum creatinine, and Model of End-Stage Liver Disease (MELD) score worsened at the end of follow up. In patient 3 there was improvement in serum albumin, porthrombin time (PT), and MELD score. Patient 4 developed radiocontrast nephropathy after the procedure, and progressed to type 1 hepatorenal syndrome and died of liver failure a few days later. Because of the major side effects seen in the last patient, the trial was prematurely stopped.CONCLUSION: Infusion of CD34+ stem cells through the hepatic artery is not safe in decompensated cirrhosis. Radiocontrast nephropathy and hepatorenal syndrome could be major side effects. However, this study doesnot preclude infusion of CD34+ stem cells through other routes.
基金The authors’research efforts were supported in part by research grants from the NIH(AT004418 to TCH)the 973 Program of Ministry of Science and Technology(MOST)of China(#2011CB707900 to TCH)+1 种基金the Scoliosis Research Society(to MJL),MKM was a recipient of Howard Hughes Medical Institute Medical Research FellowshipCS was a recipient of the Pritzker Summer Research Fellowship funded through a NIH T-35 training grant(NIDDK).
文摘Wnt signaling transduces evolutionarily conserved pathways which play important roles in initiating and regulating a diverse range of cellular activities,including cell proliferation,calcium homeostasis,and cell polarity.The role of Wnt signaling in controlling cell proliferation and stem cell self-renewal is primarily carried out through the canonical pathway,which is the best-characterized the multiple Wnt signaling branches.The past 10 years has seen a rapid expansion in our understanding of the complexity of this pathway,as many new components of Wnt signaling have been identified and linked to signaling regulation,stem cell functions,and adult tissue homeostasis.Additionally,a substantial body of evidence links Wnt signaling to tumorigenesis of cancer types and implicates it in the development of cancer drug resistance.Thus,a better understanding of the mechanisms by which dysregulation of Wnt signaling precedes the development and progression of human cancer may hasten the development of pathway inhibitors to augment current therapy.This review summarizes and synthesizes our current knowledge of the canonical Wnt pathway in development and disease.We begin with an overview of the components of the canonical Wnt signaling pathway and delve into the role this pathway has been shown to play in stemness,tumorigenesis,and cancer drug resistance.Ultimately,we hope to present an organized collection of evidence implicating Wnt signaling in tumorigenesis and chemoresistance to facilitate the pursuit of Wnt pathway modulators that may improve outcomes of cancers in which Wnt signaling contributes to aggressive disease and/or treatment resistance.
