In this study, Computational Fluid Dynamics(CFD) is used to investigate and compare the impact of bioreactor parameters(such as its geometry, medium flow-rate, scaffold configuration) on the local transport phenomena ...In this study, Computational Fluid Dynamics(CFD) is used to investigate and compare the impact of bioreactor parameters(such as its geometry, medium flow-rate, scaffold configuration) on the local transport phenomena and, hence, their impact on human mesenchymal stem cell(hM SC) expansion. The geometric characteristics of the TissueFlex174;(Zyoxel Limited, Oxford, UK) microbioreactor were considered to set up a virtual bioreactor containing alginate(in both slab and bead configuration) scaffolds. The bioreactor and scaffolds were seeded with cells that were modelled as glucose consuming entities. The widely used glucose medium, Dulbecco's Modified Eagle Medium(DMEM), supplied at two inlet flow rates of 25 and 100 μl·h^(-1), was modelled as the fluid phase inside the bioreactors. The investigation, based on applying dimensional analysis to this problem, as well as on detailed three-dimensional transient CFD results, revealed that the default bioreactor design and boundary conditions led to internal and external glucose transport, as well as shear stresses, that are conducive to h MSC growth and expansion. Furthermore, results indicated that the ‘top-inout' design(as opposed to its symmetric counterpart) led to higher shear stress for the same media inlet rate(25 μl·h^(-1)), a feature that can be easily exploited to induce shear-dependent differentiation. These findings further confirm the suitability of CFD as a robust design tool.展开更多
Salusins are regulatory peptides that affect cardiovascular function. We previously reported that salusin-a and -β protected cultured cardiomyocytes from serum deprivation-induced cell death through upregulating gluc...Salusins are regulatory peptides that affect cardiovascular function. We previously reported that salusin-a and -β protected cultured cardiomyocytes from serum deprivation-induced cell death through upregulating glucose-regulated protein 78 （GRP78）, an endoplasmic reticulum （ER） resident protein whose overexpression acts as a marker and suppressor of ER stress. The present study examined whether salusin-α and -β inhibit ER stress in ischemic myocardium. In a rat model of myocardial infarction created by ligating the left anterior descending coronary artery （LAD）, salusin-α or -β was intravenously injected at 5 or 15 nmol kg-1 15 min prior to 2 h of LAD occlusion. The high dose of salusin-α and -β3 significantly improved heart function and hemodynamics in LAD-occluded rats, but had no effects in sham-operated rats. The arrhythmias caused by LAD oc- clusion were markedly attenuated by salusin-α and -β. The apoptotic rate in ischemic myocardium was reduced from 31.5%±3.7% to 19.8%±2.2% and 12.3%±2.2%, and the infarct size was reduced from 53.4%±4.0% of the risk area to 26.5%±9.7% and 23.7%±8.9% by 15 nmol kg-1 salusin-α and -β, respectively. Furthermore, salusin-α and -β prevented the ac- tivation of GRP78 and ER stress-specific apoptotic effectors caspase-12 and CHOP （C/EBP homologous protein）, and attenu- ated the reduction of an ER stress-associated antiapoptotic protein Bcl-2 in ischemic cardiac tissue. The salusins also inhibited the ER stress induced by tunicamycin in cultured rat H9c2 cardiomyocytes. These results indicate that salusins protect myo- cardium against ischemic injury by inhibiting ER stress and ER stress-associated apoptosis.展开更多
基金Department of Engineering Science, University of Oxford, Scholarship
文摘In this study, Computational Fluid Dynamics(CFD) is used to investigate and compare the impact of bioreactor parameters(such as its geometry, medium flow-rate, scaffold configuration) on the local transport phenomena and, hence, their impact on human mesenchymal stem cell(hM SC) expansion. The geometric characteristics of the TissueFlex174;(Zyoxel Limited, Oxford, UK) microbioreactor were considered to set up a virtual bioreactor containing alginate(in both slab and bead configuration) scaffolds. The bioreactor and scaffolds were seeded with cells that were modelled as glucose consuming entities. The widely used glucose medium, Dulbecco's Modified Eagle Medium(DMEM), supplied at two inlet flow rates of 25 and 100 μl·h^(-1), was modelled as the fluid phase inside the bioreactors. The investigation, based on applying dimensional analysis to this problem, as well as on detailed three-dimensional transient CFD results, revealed that the default bioreactor design and boundary conditions led to internal and external glucose transport, as well as shear stresses, that are conducive to h MSC growth and expansion. Furthermore, results indicated that the ‘top-inout' design(as opposed to its symmetric counterpart) led to higher shear stress for the same media inlet rate(25 μl·h^(-1)), a feature that can be easily exploited to induce shear-dependent differentiation. These findings further confirm the suitability of CFD as a robust design tool.
基金supported by the National Basic Research Program of China (Grant Nos. 2006CB503807 and 2009CB521902)the National Natural Science Foundation of China (Grant Nos. 30600763, 30870906, and 31071023)+2 种基金the Pujiang Project of Shanghai, China (Grant No.08PJ14001)the Project Sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars, Ministry of Education of China (Grant No. [2008]891)the Fund for Outstanding Young Teachers in Higher Education Institutions of Shanghai, China (Grant No.[2009]63)
文摘Salusins are regulatory peptides that affect cardiovascular function. We previously reported that salusin-a and -β protected cultured cardiomyocytes from serum deprivation-induced cell death through upregulating glucose-regulated protein 78 （GRP78）, an endoplasmic reticulum （ER） resident protein whose overexpression acts as a marker and suppressor of ER stress. The present study examined whether salusin-α and -β inhibit ER stress in ischemic myocardium. In a rat model of myocardial infarction created by ligating the left anterior descending coronary artery （LAD）, salusin-α or -β was intravenously injected at 5 or 15 nmol kg-1 15 min prior to 2 h of LAD occlusion. The high dose of salusin-α and -β3 significantly improved heart function and hemodynamics in LAD-occluded rats, but had no effects in sham-operated rats. The arrhythmias caused by LAD oc- clusion were markedly attenuated by salusin-α and -β. The apoptotic rate in ischemic myocardium was reduced from 31.5%±3.7% to 19.8%±2.2% and 12.3%±2.2%, and the infarct size was reduced from 53.4%±4.0% of the risk area to 26.5%±9.7% and 23.7%±8.9% by 15 nmol kg-1 salusin-α and -β, respectively. Furthermore, salusin-α and -β prevented the ac- tivation of GRP78 and ER stress-specific apoptotic effectors caspase-12 and CHOP （C/EBP homologous protein）, and attenu- ated the reduction of an ER stress-associated antiapoptotic protein Bcl-2 in ischemic cardiac tissue. The salusins also inhibited the ER stress induced by tunicamycin in cultured rat H9c2 cardiomyocytes. These results indicate that salusins protect myo- cardium against ischemic injury by inhibiting ER stress and ER stress-associated apoptosis.
