Parathyroid hormone(PTH) is well-known as the principal regulator of calcium homeostasis in the human body and controls bone metabolism via actions on the survival and activation of osteoblasts. The intermittent admin...Parathyroid hormone(PTH) is well-known as the principal regulator of calcium homeostasis in the human body and controls bone metabolism via actions on the survival and activation of osteoblasts. The intermittent administration of PTH has been shown to stimulate bone production in mice and men and therefore PTH administration has been recently approved for the treatment of osteoporosis. Besides to its physiological role in bone remodelling PTH has been demonstrated to influence and expand the bone marrow stem cell niche where hematopoietic stem cells, capable of both self-renewal and differentiation, reside. Moreover, intermittent PTH treatment is capable to induce mobilization of progenitor cells from the bone marrow into the bloodstream. This novel function of PTH on modulating the activity of the stem cell niche in the bone marrow as well as on mobilization and regeneration of bone marrow-derived stem cells offers new therapeutic options in bone marrow and stem cell transplantation as well as in the field of ischemic disorders.展开更多
Basic research on pluripotent stem cells is designed to enhance understanding of embryogenesis, whereas applied research is designed to develop novel therapies and prevent diseases. Attainment of these goals has been ...Basic research on pluripotent stem cells is designed to enhance understanding of embryogenesis, whereas applied research is designed to develop novel therapies and prevent diseases. Attainment of these goals has been enhanced by the establishment of embryonic stem cell lines, the technological development of genomic reprogramming to generate induced-pluripotent stem cells, and improvements in in vitro techniques to manipulate stem cells. This review summarizes the techniques required to generate neural cells from pluripotent stem cells. In particular, this review describes current research applications of a simple neural differentiation method, the neural stem sphere method, which we developed.展开更多
The complement pathway is best known for its role in immune surveillance and inflammation. However,its ability of opsonizing and removing not only pathogens,but also necrotic and apoptotic cells,is a phylogenetically ...The complement pathway is best known for its role in immune surveillance and inflammation. However,its ability of opsonizing and removing not only pathogens,but also necrotic and apoptotic cells,is a phylogenetically ancient means of initiating tissue repair. The means and mechanisms of complement-mediated tissue repair are discussed in this review. There is increasing evidence that complement activation contributes to tissue repair at several levels. These range from the chemo-attraction of stem and progenitor cells to areas of complement activation,to increased survival of various cell types in the presence of split products of complement,and to the production of trophic factors by cells activated by the anaphylatoxins C3 a and C5 a. This repair aspect of complement biology has not found sufficient appreciation until recently. The following will examine this aspect of complement biology with an emphasis on the anaphylatoxins C3 a and C5 a.展开更多
Cell reprograming technologies have broad applications in cell therapy,disease modeling and drug screening.Direct reprogramming is the process of converting from one cell type into a very distantly related cell type.I...Cell reprograming technologies have broad applications in cell therapy,disease modeling and drug screening.Direct reprogramming is the process of converting from one cell type into a very distantly related cell type.In this direct conversion process,cells do not proceed through a pluripotent stage,which can be time-consuming and challenging due to spontaneous differentiation.This method also offers the advantage of circumventing the teratoma potential that is associated with using iPSCs.Previous works have demonstrated that with the use of genetic manipulation,fibroblasts can be directly converted into other cell types,including neurons,cardiomyocytes,blood cell progenitors,and hepatocytes.It is well known that the microenvironment can directs cell fate,and in turn cells interact with or remodel their niches.Accumulative evidence suggests that biophysical factors such as the microtopography and mechanical property of cell adhesive substrates regulate a variety of cellular functions such as migration,proliferation and differentiation,which in turn can modulate wound healing,tissue remodeling and tumor growth,but there are limited number of studies on the roles of biophysical cues in cell reprogramming[1].Passive topographical cues offer a simple and effective method to improve reprogramming efficiency without the need for biochemical manipulations.Our previous study has demonstrated that somatic cells cultured on the parallel microgrooves,which can replace the effects of small-molecule epigenetic modifiers and significantly improve the iPSCs reprogramming efficiency.The mechanism relies on the mechanomodulation of the cells’epigenetic state,specifically,an increase of histone H3 acetylation and H3K4 methylation[2].Additionally,in cardiomyocytes reprogramming study,culturing the fibroblasts on microgrooved substrate enhances the expression of cardiomyocyte genes by day 2 and improves the yield of partially reprogrammed cells at day 10.By combining microgrooved substrate with an optimized culture protocol,the conv展开更多
Endogenous "stem cell niche"(SCN) accompanying vessels contains immune system components which in vivo determine differentiation of multi potent stem cells toward proper cell types in given tissue. Combinati...Endogenous "stem cell niche"(SCN) accompanying vessels contains immune system components which in vivo determine differentiation of multi potent stem cells toward proper cell types in given tissue. Combinations of sex steroids may represent novel chemical approach for neuronal areas of regenerative medicine,since they cause transformation of vascular smooth muscle stem cells into differentiating neuronal cells. Circulating sex steroids are present during pregnancy and can be utilized where needed,when various embryonic/fetal tissues develop from their stem cells. Utilization of induced regeneration of tissues(regenerative medicine) is expected being more effective in sudden failures of younger individuals carrying intact SCN,as compared to established chronic disorders caused by SCN alteration. An essential component of SCN are monocyte-derived cells exhibiting tissue-specific "stop effect"(SE) preventing,for instance,an aging of neuronal cells. Its alteration causes that implantation of neuronal stem cells will also result in their differentiation toward aging cells. When we repair the SE by supply of circulating mononuclear cells from young healthy individuals,we may be able to provide novel regenerative treatments of age-induced neural diseases by sex steroid combinations. Questions regarding some age-induced body alterations are also addressed.展开更多
Stem cells are of global excitement for various diseases including heart diseases. It is worth to understand the mechanism or role of stem cells in the treatment of heart failure. Bone marrow derived stem cells are co...Stem cells are of global excitement for various diseases including heart diseases. It is worth to understand the mechanism or role of stem cells in the treatment of heart failure. Bone marrow derived stem cells are commonly practiced with an aim to improve the function of the heart. The majority of studies have been conducted with acute myocardial infarction and a few has been investigated with the use of stem cells for treating chronic or dilated cardiomyopathy. Heterogeneity in the treated group using stem cells has greatly emerged. Ever increasing demand for any alternative made is of at most priority for cardiomyopathy. Stem cells are of top priority with the current impact that has generated among physicians. However,meticulous selection of proper source is required since redundancy is clearly evident with the present survey. This review focuses on the methods adopted using stem cells for heart diseases and outcomes that are generated so far with an idea to determine the best therapeutic possibility in order to fulfill the present demand.展开更多
OBJECTIVE 3,5-Dimethoxy-4-(2-amino-3-prop-2-ynylsulfanyl-propionyl)-benzoic acid 4-guanidino-butyl ester(ZYZ451)showed excellent cardio-protective effects in our previous work.However,its therapeutic potential in vivo...OBJECTIVE 3,5-Dimethoxy-4-(2-amino-3-prop-2-ynylsulfanyl-propionyl)-benzoic acid 4-guanidino-butyl ester(ZYZ451)showed excellent cardio-protective effects in our previous work.However,its therapeutic potential in vivo and the mechanism remained to be elucidated.Herein,we evaluated cardiac protective role of ZYZ451 in post-myocardial infarction(post-MI)rats,and elucidated the underlying mechanism.METHODS Neonatal rat ventricular cardiomyoctys(NRVCs)were separated and subjected to pre-deoxidized(1%O2,5%CO2),and serum-free medium for 4h to obtain ischemic model.Mitochondrial ROS,MnSOD activity and cell apoptosis were tested to verify the cardiac protective effects of ZYZ451.Inhibitors and siRNA for Stat3 were used to determine role of Stat3 played in cardio-protective effectes of ZYZ451.Mitochondria were isolated from NRVCs to determine expression of Stat3 and MnSOD.Immunofluorescence and coimmunoprecipitation were conducted to determine the interaction between MnSOD and Stat3.To apply post-MI model in rats,the rats were subjected to ligation of LAD except for control group.The vehicle or ZYZ451(1,2or 5mg·kg-1)or mixture of Leonurine and SPRC(15mg·kg-1)was administered 7dbefore and 3more days after the operation.Area at risk(AAR),apoptosis in AAR,LDH and MDA levels,and MnSOD activity and expression were detected to evaluate the cardiac injury.Tissue mitochondria were isolated to determine MnSOD and Stat3 expression in ischemia,and coimmunoprecipitaion was performed to verify the interaction between MnSOD and Stat3 in vivo.RESULTS ZYZ451 prevented hypoxia induced NRVCs apoptosis via increasing MnSOD activity and inhibiting mitochondrial ROS production.Interestingly,5,15-DPP(STAT3phosphorylation inhibitor)failed to inhibit MnSOD activity,while knockout of STAT3 resulted in significant reduction of MnSOD activity,followed by increased mitochondrial ROS production and cardiomyocytes apoptosis in hypoxia.Moreover,protective effects of ZYZ451 were blunted in Stat3 deficient NRVCs.These results indicated the necessity of展开更多
文摘Parathyroid hormone(PTH) is well-known as the principal regulator of calcium homeostasis in the human body and controls bone metabolism via actions on the survival and activation of osteoblasts. The intermittent administration of PTH has been shown to stimulate bone production in mice and men and therefore PTH administration has been recently approved for the treatment of osteoporosis. Besides to its physiological role in bone remodelling PTH has been demonstrated to influence and expand the bone marrow stem cell niche where hematopoietic stem cells, capable of both self-renewal and differentiation, reside. Moreover, intermittent PTH treatment is capable to induce mobilization of progenitor cells from the bone marrow into the bloodstream. This novel function of PTH on modulating the activity of the stem cell niche in the bone marrow as well as on mobilization and regeneration of bone marrow-derived stem cells offers new therapeutic options in bone marrow and stem cell transplantation as well as in the field of ischemic disorders.
基金Supported by Grant-in-Aid for Young Scientists(B),No.24791230Research Grant for long-range research initiative from JCIA+1 种基金Selective Research Fund of Tokyo Metropolitan Universitya Grant-in-Aid for Scientific Research,No.20500339
文摘Basic research on pluripotent stem cells is designed to enhance understanding of embryogenesis, whereas applied research is designed to develop novel therapies and prevent diseases. Attainment of these goals has been enhanced by the establishment of embryonic stem cell lines, the technological development of genomic reprogramming to generate induced-pluripotent stem cells, and improvements in in vitro techniques to manipulate stem cells. This review summarizes the techniques required to generate neural cells from pluripotent stem cells. In particular, this review describes current research applications of a simple neural differentiation method, the neural stem sphere method, which we developed.
基金Supported by The grants R21 HL094878 and R21AI10950 to IUS and RGD
文摘The complement pathway is best known for its role in immune surveillance and inflammation. However,its ability of opsonizing and removing not only pathogens,but also necrotic and apoptotic cells,is a phylogenetically ancient means of initiating tissue repair. The means and mechanisms of complement-mediated tissue repair are discussed in this review. There is increasing evidence that complement activation contributes to tissue repair at several levels. These range from the chemo-attraction of stem and progenitor cells to areas of complement activation,to increased survival of various cell types in the presence of split products of complement,and to the production of trophic factors by cells activated by the anaphylatoxins C3 a and C5 a. This repair aspect of complement biology has not found sufficient appreciation until recently. The following will examine this aspect of complement biology with an emphasis on the anaphylatoxins C3 a and C5 a.
基金supported in part by a grant from the National Institute of Health ( HL121450)UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Innovation Award
文摘Cell reprograming technologies have broad applications in cell therapy,disease modeling and drug screening.Direct reprogramming is the process of converting from one cell type into a very distantly related cell type.In this direct conversion process,cells do not proceed through a pluripotent stage,which can be time-consuming and challenging due to spontaneous differentiation.This method also offers the advantage of circumventing the teratoma potential that is associated with using iPSCs.Previous works have demonstrated that with the use of genetic manipulation,fibroblasts can be directly converted into other cell types,including neurons,cardiomyocytes,blood cell progenitors,and hepatocytes.It is well known that the microenvironment can directs cell fate,and in turn cells interact with or remodel their niches.Accumulative evidence suggests that biophysical factors such as the microtopography and mechanical property of cell adhesive substrates regulate a variety of cellular functions such as migration,proliferation and differentiation,which in turn can modulate wound healing,tissue remodeling and tumor growth,but there are limited number of studies on the roles of biophysical cues in cell reprogramming[1].Passive topographical cues offer a simple and effective method to improve reprogramming efficiency without the need for biochemical manipulations.Our previous study has demonstrated that somatic cells cultured on the parallel microgrooves,which can replace the effects of small-molecule epigenetic modifiers and significantly improve the iPSCs reprogramming efficiency.The mechanism relies on the mechanomodulation of the cells’epigenetic state,specifically,an increase of histone H3 acetylation and H3K4 methylation[2].Additionally,in cardiomyocytes reprogramming study,culturing the fibroblasts on microgrooved substrate enhances the expression of cardiomyocyte genes by day 2 and improves the yield of partially reprogrammed cells at day 10.By combining microgrooved substrate with an optimized culture protocol,the conv
文摘Endogenous "stem cell niche"(SCN) accompanying vessels contains immune system components which in vivo determine differentiation of multi potent stem cells toward proper cell types in given tissue. Combinations of sex steroids may represent novel chemical approach for neuronal areas of regenerative medicine,since they cause transformation of vascular smooth muscle stem cells into differentiating neuronal cells. Circulating sex steroids are present during pregnancy and can be utilized where needed,when various embryonic/fetal tissues develop from their stem cells. Utilization of induced regeneration of tissues(regenerative medicine) is expected being more effective in sudden failures of younger individuals carrying intact SCN,as compared to established chronic disorders caused by SCN alteration. An essential component of SCN are monocyte-derived cells exhibiting tissue-specific "stop effect"(SE) preventing,for instance,an aging of neuronal cells. Its alteration causes that implantation of neuronal stem cells will also result in their differentiation toward aging cells. When we repair the SE by supply of circulating mononuclear cells from young healthy individuals,we may be able to provide novel regenerative treatments of age-induced neural diseases by sex steroid combinations. Questions regarding some age-induced body alterations are also addressed.
文摘Stem cells are of global excitement for various diseases including heart diseases. It is worth to understand the mechanism or role of stem cells in the treatment of heart failure. Bone marrow derived stem cells are commonly practiced with an aim to improve the function of the heart. The majority of studies have been conducted with acute myocardial infarction and a few has been investigated with the use of stem cells for treating chronic or dilated cardiomyopathy. Heterogeneity in the treated group using stem cells has greatly emerged. Ever increasing demand for any alternative made is of at most priority for cardiomyopathy. Stem cells are of top priority with the current impact that has generated among physicians. However,meticulous selection of proper source is required since redundancy is clearly evident with the present survey. This review focuses on the methods adopted using stem cells for heart diseases and outcomes that are generated so far with an idea to determine the best therapeutic possibility in order to fulfill the present demand.
基金The project supported by National Natural Science Foundation of China(81330080)Key laboratory program of the Education Commission of Shanghai Municipality(ZDSYS14005)Shanghai Committee of Science and Technology(14JC1401100)
文摘OBJECTIVE 3,5-Dimethoxy-4-(2-amino-3-prop-2-ynylsulfanyl-propionyl)-benzoic acid 4-guanidino-butyl ester(ZYZ451)showed excellent cardio-protective effects in our previous work.However,its therapeutic potential in vivo and the mechanism remained to be elucidated.Herein,we evaluated cardiac protective role of ZYZ451 in post-myocardial infarction(post-MI)rats,and elucidated the underlying mechanism.METHODS Neonatal rat ventricular cardiomyoctys(NRVCs)were separated and subjected to pre-deoxidized(1%O2,5%CO2),and serum-free medium for 4h to obtain ischemic model.Mitochondrial ROS,MnSOD activity and cell apoptosis were tested to verify the cardiac protective effects of ZYZ451.Inhibitors and siRNA for Stat3 were used to determine role of Stat3 played in cardio-protective effectes of ZYZ451.Mitochondria were isolated from NRVCs to determine expression of Stat3 and MnSOD.Immunofluorescence and coimmunoprecipitation were conducted to determine the interaction between MnSOD and Stat3.To apply post-MI model in rats,the rats were subjected to ligation of LAD except for control group.The vehicle or ZYZ451(1,2or 5mg·kg-1)or mixture of Leonurine and SPRC(15mg·kg-1)was administered 7dbefore and 3more days after the operation.Area at risk(AAR),apoptosis in AAR,LDH and MDA levels,and MnSOD activity and expression were detected to evaluate the cardiac injury.Tissue mitochondria were isolated to determine MnSOD and Stat3 expression in ischemia,and coimmunoprecipitaion was performed to verify the interaction between MnSOD and Stat3 in vivo.RESULTS ZYZ451 prevented hypoxia induced NRVCs apoptosis via increasing MnSOD activity and inhibiting mitochondrial ROS production.Interestingly,5,15-DPP(STAT3phosphorylation inhibitor)failed to inhibit MnSOD activity,while knockout of STAT3 resulted in significant reduction of MnSOD activity,followed by increased mitochondrial ROS production and cardiomyocytes apoptosis in hypoxia.Moreover,protective effects of ZYZ451 were blunted in Stat3 deficient NRVCs.These results indicated the necessity of
