AIM:To investigate the effects of diammonium glycyrrhizinate(Gly)on portal hypertension(PHT)in isolated portal perfused rat liver(IPPRL)with carbon tetrachloride(CCl4)-induced chronic hepatitis.METHODS:PHT model was r...AIM:To investigate the effects of diammonium glycyrrhizinate(Gly)on portal hypertension(PHT)in isolated portal perfused rat liver(IPPRL)with carbon tetrachloride(CCl4)-induced chronic hepatitis.METHODS:PHT model was replicated with CCl4 in rats for 84 d.Model was identified by measuring the ascetic amounts,hepatic function,portal pressure in vivo,splenic index,and pathological alterations.Inducible nitric oxide synthase(iNOS)in liver was assessed by immunohistochemistry.IPPRLs were performed at d0,d28,d56,and d84.After phenylephrine-induced constriction,Gly was geometrically used to reduce PHT.Gly action was expressed as median effective concentration(EC50)and area under the curve(AUC).Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads.RESULTS:PHT model was confirmed with ascites,splenomegaly,serum biomarkers of hepatic injury,and elevated portal pressure.Pathological findings had shown normal hepatic structure at d0,degenerations at d28,fibrosis at d56,cirrhosis at d84in PHT rats.Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development.Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis.Gly potencies were increased gradually along with PHT development,characterized with its EC50at 2.80×10-10,3.03×10-11,3.77×10-11and 4.65×10-11mol/L at d0,d28,d56and d84,respectively.Existed iNOS was located at hepatocyte at d0,stellate cells at d28,stellate cells and macrophages at d56,and macrophages in portal triads at d84.Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development.AUC values of Gly were positively correlated with existed iNOS levels in portal triads.CONCLUSION:Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis.The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads.展开更多
<Abstract>Effects of amniotic fluid embolism-like plasma (AFEP) on the isolated perfused rabbit lungs (IPRL)were studied. It was found that AFEP could induce elevation of pulmonary artery pressure (PAP) and deve...<Abstract>Effects of amniotic fluid embolism-like plasma (AFEP) on the isolated perfused rabbit lungs (IPRL)were studied. It was found that AFEP could induce elevation of pulmonary artery pressure (PAP) and development of lung edema, which could be partially prevented by ibuprofen, a cycloxygenase inhibit0r, but amniotic fluid itself could not cause elevation of PAP and lung edema. The result suggests that AFEP-induced mediator from whole blood cells may be the important factor resulting in above-mentioned pathological changes.展开更多
Introduction:3D bio-printing technology<sup>[1-3]</sup>（Figure 1）capable of dispensing live cells,soluble factors,and phase-changing hydrogel in a desired pattern,has great potential in creating 3D tissu...Introduction:3D bio-printing technology<sup>[1-3]</sup>（Figure 1）capable of dispensing live cells,soluble factors,and phase-changing hydrogel in a desired pattern,has great potential in creating 3D tissue.However,maintaining the viability of a thick tissue structure during tissue growth and maturation is challenging due to lack of adequate vascular perfusion.In a simple tissue model with展开更多
BACKGROUND The machine perfusion(MP)preservation including hypothermic MP(HMP)and midthermic MP(MMP)has been considered as a promising strategy to preserve the functions of liver donated after cardiac death.The import...BACKGROUND The machine perfusion(MP)preservation including hypothermic MP(HMP)and midthermic MP(MMP)has been considered as a promising strategy to preserve the functions of liver donated after cardiac death.The importance of understanding liver sinusoidal endothelial cells(LSEC)damage in regulating liver injury during MP has been emphasized.However,the ultrastructural changes in the LSEC and sinusoids around them after MP are unclear.AIM To investigate the ultrastructural changes in the LSEC and sinusoids around them after MP.METHODS Porcine liver grafts undergo a warm ischemia time of 60 minutes perfused for 4 h with modified University of Wisconsin gluconate solution.Group A grafts were preserved with HMP at 8℃ constantly for 4 h.Group B grafts were preserved with a rewarming solution at 22℃ by MMP for 4 h.Then the ultrastructural changes in the LSEC and sinusoids in Group A and B were comparatively analyzed by using osmium-maceration scanning electron microscopy with complementary transmission electron microscopy methods.RESULTS An analysis of the LSEC after warm ischemia revealed that mitochondria with condensed-shaped cristae,abnormal vesicles,reduction of ribosomes and the endoplasmic reticulum(ER)surround the mitochondria appeared.The MP subsequent after warm ischemia alleviate the abnormal vesicles and reduction of ribosomes in LSEC,which indicated the reduction of the ER damage.However,MMP could restore the tubular mitochondrial cristae,while after HMP the condensed and narrow mitochondrial cristae remained.In addition,the volume of the sinusoidal space in the liver grafts after MMP were restored,which indicated a lower risk of pressure injury than HMP.CONCLUSION MMP alleviates the ER damage of LSEC by warm ischemia,additionally restore the metabolism of LSEC via the normalization of mitochondria and prevent the share stress damage of liver grafts.展开更多
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
Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may...Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.展开更多
Ischemia-reperfusion injury (IRI) is an inherent issue in organ transplantation. Because of the allograft shortage, more and more extended criteria donor (ECD) organs are used, unfortunately these grafts are more susc...Ischemia-reperfusion injury (IRI) is an inherent issue in organ transplantation. Because of the allograft shortage, more and more extended criteria donor (ECD) organs are used, unfortunately these grafts are more susceptible to IRI. Although machine perfusion technology has brought hope to alleviate IRI, this technology is still unable to eradicate IRI-related organ damage. Ischemia-free liver transplantation (IFLT)can completely avoid IRI, thereby improve graft function and recipient outcome, and allow to expand organ pool. This review summarized the latest progresses in IFLT, and speculated the future development of this concept.展开更多
BACKGROUND Ischemic heart disease(IHD)impacts the quality of life and has the highest mortality rate of cardiovascular diseases globally.AIM To compare variations in the parameters of the single-lead electrocardiogram...BACKGROUND Ischemic heart disease(IHD)impacts the quality of life and has the highest mortality rate of cardiovascular diseases globally.AIM To compare variations in the parameters of the single-lead electrocardiogram(ECG)during resting conditions and physical exertion in individuals diagnosed with IHD and those without the condition using vasodilator-induced stress computed tomography(CT)myocardial perfusion imaging as the diagnostic reference standard.METHODS This single center observational study included 80 participants.The participants were aged≥40 years and given an informed written consent to participate in the study.Both groups,G1(n=31)with and G2(n=49)without post stress induced myocardial perfusion defect,passed cardiologist consultation,anthropometric measurements,blood pressure and pulse rate measurement,echocardiography,cardio-ankle vascular index,bicycle ergometry,recording 3-min single-lead ECG(Cardio-Qvark)before and just after bicycle ergometry followed by performing CT myocardial perfusion.The LASSO regression with nested cross-validation was used to find the association between Cardio-Qvark parameters and the existence of the perfusion defect.Statistical processing was performed with the R programming language v4.2,Python v.3.10[^R],and Statistica 12 program.RESULTS Bicycle ergometry yielded an area under the receiver operating characteristic curve of 50.7%[95%confidence interval(CI):0.388-0.625],specificity of 53.1%(95%CI:0.392-0.673),and sensitivity of 48.4%(95%CI:0.306-0.657).In contrast,the Cardio-Qvark test performed notably better with an area under the receiver operating characteristic curve of 67%(95%CI:0.530-0.801),specificity of 75.5%(95%CI:0.628-0.88),and sensitivity of 51.6%(95%CI:0.333-0.695).CONCLUSION The single-lead ECG has a relatively higher diagnostic accuracy compared with bicycle ergometry by using machine learning models,but the difference was not statistically significant.However,further investigations are required to uncover the hidden capabilities of single-lead ECG in IHD diagnosis.展开更多
Bioelectronic interventions,specifically trigeminal nerve st imulat ion(TNS),have attracted considerable attention in conditions where cortical spreading depolarizations(CSDs)accompanied by compromised cerebral perfus...Bioelectronic interventions,specifically trigeminal nerve st imulat ion(TNS),have attracted considerable attention in conditions where cortical spreading depolarizations(CSDs)accompanied by compromised cerebral perfusion may exacerbate neurological damage.While pharmacological interventions have demonstrated initial potential in addressing CSDs,a standardized treatment approach has not yet been established.The objective of this perspective is to explore emerging bioelectronic methodologies for addressing CSDs,particularly emphasizing TNS,and to underscore TNS’s capacity to enhance neurovascular coupling and cerebral perfusion.展开更多
Temperature as an indicator of tissue response is widely used in clinical applications. In view of above a problem of temperature distribution in peripheral regions of extended spherical organs of a human body like, h...Temperature as an indicator of tissue response is widely used in clinical applications. In view of above a problem of temperature distribution in peripheral regions of extended spherical organs of a human body like, human breast involving uniformly perfused tumor is investigated in this paper. The human breast is assumed to be spherical in shape with upper hemisphere projecting out from the trunk of the body and lower hemisphere is considered to be a part of the body core. The outer surface of the breast is assumed to be exposed to the environment from where the heat loss takes place by conduction, convection, radiation and evaporation. The heat transfer from core to the surface takes place by thermal conduction and blood perfusion. Also metabolic activity takes place at different rates in different layers of the breast. An elliptical-shaped tumor is assumed to be present in the dermis region of human breast. A finite element model is developed for a two-dimensional steady state case incorporating the important parameters like blood flow, metabolic activity and thermal conductivity. The triangular ring elements are employed to discretize the region. Appropriate boundary conditions are framed using biophysical conditions. The numerical results are used to study the effect of tumor on temperature distribution in the region.展开更多
Myocardial ischemia is the most common and primary cause of myocardium damage. Numerous conventional techniques and methods have been developed for ischemia and reperfusion studies. However, because of damage to the h...Myocardial ischemia is the most common and primary cause of myocardium damage. Numerous conventional techniques and methods have been developed for ischemia and reperfusion studies. However, because of damage to the heart sample, most of these techniques can not be used to continuously monitor the full dynamic course of the myocardial metabolic pathway. The nuclear magnetic resonnance (NMR) surface coil technique, which overcomes the limitations of conventional instrumentation, can be used to quantitatively study every stage of the perfused heart (especially after perfusion stoppage) continuously, dynamically, and without damage under normal or designed physiological conditions at the molecular level. In this paper, 31 P NMR was used to study the effects of ischemia and hypoxia on isolated perfused hearts. The results show that complete hypoxia caused more severe functional damage to the myocardial cells than complete ischemia.展开更多
Post-reperfusion syndrome(PRS)in liver transplant recipients remains one of the most dreaded complications in liver transplant surgery.PRS can impact the short-term and long-term patient and graft outcomes.The definit...Post-reperfusion syndrome(PRS)in liver transplant recipients remains one of the most dreaded complications in liver transplant surgery.PRS can impact the short-term and long-term patient and graft outcomes.The definition of PRS has evolved over the years,from changes in arterial blood pressures and heart and/or de-creases in the systemic vascular resistance and cardiac output to including the fibrinolysis and grading the severity of PRS.However,all that did not reflect on the management of PRS or its impact on the outcomes.In recent years,new scientific techniques and new technology have been in the pipeline to better understand,manage and maybe prevent PRS.These new methods and techniques are still in the infancy,and they have to be proven not in prevention and management of PRS but their effects in the patient and graft outcomes.In this article,we will review the long history of PRS,its definition,etiology,mana-gement and most importantly the new advances in science and technology to prevent and properly manage PRS.展开更多
BACKGROUND Traditional limitations of cold static storage(CSS)on ice at 4℃during lung transplantation have necessitated limiting cold ischemic time(CIT)to 4-6 hours.Ex vivo lung perfusion(EVLP)can extend this preserv...BACKGROUND Traditional limitations of cold static storage(CSS)on ice at 4℃during lung transplantation have necessitated limiting cold ischemic time(CIT)to 4-6 hours.Ex vivo lung perfusion(EVLP)can extend this preservation time through the suspension of CIT and normothermic perfusion.As we continue to further expand the donor pool in all aspects of lung transplantation,teams are frequently traveling further distances to procure organs.AIM To determine the effect of CSS or EVLP on donors with extended travel distance[>750 nautical miles(NM)]to recipient.METHODS Lung transplants,whose donor traveled greater than 750 NM,were identified from the United Network for Organ Sharing Database.Recipients were stratified into either:CSS or EVLP,based on preservation method.Groups were assessed with comparative statistics and survival was assessed by Kaplan-Meier methods.A 3:1 propensity match was then created,and same analysis was repeated.RESULTS Prior to matching,those in the EVLP group had significantly increased postoperative morbidity to include dialysis,ventilator use,acute rejection,and treated rejection in the first year(P<0.05 for all).However,there were no significant differences in midterm survival(P=0.18).Following matching,those in the EVLP group again had significantly increased post-operative morbidity to include dialysis,extracorporeal membrane oxygenation use,ventilator use,and treated rejection in the first year(P<0.05 for all).As before,there were no significant differences in midterm survival following matching(P=0.08).CONCLUSION While there was no significant difference in survival,EVLP patients had increased peri-operative morbidity.With the advent of changes in CSS with 10℃storage further analysis is necessary to evaluate the best methods for utilizing organs from increased distances.展开更多
BACKGROUND Liver transplantation(LT)is the only curative,life-saving option for children and adults with end-stage liver disease.Due to the well-known shortage and heterogeneity of grafts,split LT(SLT)is an attractive...BACKGROUND Liver transplantation(LT)is the only curative,life-saving option for children and adults with end-stage liver disease.Due to the well-known shortage and heterogeneity of grafts,split LT(SLT)is an attractive strategy to expand the donor pool and reduce waitlist times.Given increased risk of cold ischemia time with SLT,machine perfusion represents a promising option to reduce it and optimize transplant logistics and outcomes.The present communication describes various possible combinations of procurement steps to perform SLT facilitated by placing one or both grafts on a normothermic machine perfusion(NMP)closed circuit device.CASE SUMMARY A 19-month-old female with biliary atresia after failed Kasai portoenterostomy and a 42-year-old woman with unresectable intrahepatic cholangiocarcinoma were selected as recipients for a SLT from a 17-year-old male donor.The SLT generated a left lateral segment and a right trisectional graft of appropriate volume for both recipients.After a mixed in-situ and ex-situ split,in order to improve logistics,the right trisectional graft was placed on a closed circuit NMP device,following an appropriate vascular reconstruction.Both grafts were implanted with excellent short-term outcomes.CONCLUSION Use of NMP with SLT for preservation prior to implantation allows not only for graft optimization but also for significant improvement of transplant logistics.We propose various models and standardization of logistic options for combining SLT with NMP to optimize graft availability and outcomes.展开更多
BACKGROUND Contrast-enhanced ultrasonography(CEUS)is utilized to assess the therapeutic efficacy of interventional therapy in liver cancer patients,offering insights into tumor blood flow changes,angiogenesis,and tumo...BACKGROUND Contrast-enhanced ultrasonography(CEUS)is utilized to assess the therapeutic efficacy of interventional therapy in liver cancer patients,offering insights into tumor blood flow changes,angiogenesis,and tumor markers.AIM To evaluate the use of CEUS in examining the effectiveness of interventional therapy for liver cancer,we aim to investigate its diagnostic utility for tumor perfusion patterns,microvessel density,perfusion recovery,blood flow enhancement response,and alterations in tumor markers among patients receiving interventional therapy for liver cancer.METHODS The study involved 124 patients who underwent interventional therapy for liver cancer at Guangzhou First People’s Hospital from January 2022 to February 2024.All patients were examined using CEUS before treatment and at 1 month,3 months,and 6 months,and the concentrations of tumor markers were collected and statistically analyzed using Statistical Package for the Social Sciences 25.0.Receiver operating characteristic(ROC)curves were used to evaluate the diagnostic efficacy of CEUS and analyze its sensitivity,specificity,and correlation with clinical indicators.RESULTS Before treatment,tumor blood flow was primarily enhanced.After treatment,enhanced perfusion declined,while uniform and non-uniform perfusion increased,indicating reduced tumor activity.Enhanced perfusion decreased from 68.25%before treatment to 53.75%at 6 months post-treatment(F=6.123,P=0.016),indicating reduced tumor activity.The microvessel density of the tumors decreased significantly after treatment(P<0.05),and the proportion of low microvessel density increased.After treatment,perfusion recovery in the tumor area improved,the proportion of complete and partial responses gradually increased,and the proportion of stable lesions decreased(P<0.05).The levels of alphafetoprotein,carcinoembryonic antigen,and carbohydrate antigen 19-9 decreased by 68.7%,30.4%,and 41.6%,respectively,at 6 months post-treatment(P<0.05).CEUS showed a sensitivity of 85.72%,specificity of 92.31%,and area under the curve of 0.911(95%CI:0.883–0.939)for evaluating treatment response.ROC curve analysis showed that CEUS had high sensitivity and specificity and could effectively evaluate the efficacy of interventional therapy for liver cancer.CONCLUSION CEUS has high diagnostic value in evaluating therapeutic effects in patients with liver cancer following interventional therapy.It can reflect changes in tumor blood flow,angiogenesis,and tumor marker levels,providing an effective basis for real-time monitoring of treatment outcomes.展开更多
BACKGROUND The normothermic machine perfusion pump(NMPP)could shape the future of transplantation.Providing ex-vivo optimization,NMPP attenuates ischemic insult while replenishing energy.An understanding of machine pe...BACKGROUND The normothermic machine perfusion pump(NMPP)could shape the future of transplantation.Providing ex-vivo optimization,NMPP attenuates ischemic insult while replenishing energy.An understanding of machine perfusion time(MPT)impact and potential clinical benefits is paramount and necessitates exploration.AIM To investigate the relationship between MPT and post-transplant graft function.METHODS Retrospective review of the first 50 donation after circulatory death(DCD)grafts preserved using NMPP in a tertiary institution was performed.Essential preser-vation time points,graft parameters,recipient information,and postoperative outcomes were prospectively recorded.Early allograft dysfunction(EAD),L-Graft7 score and 90-day outcomes were collected for all grafts.The first 20 re-cipients were allocated into the early group,considered the learning curve population for the center.The subsequent 30 were allocated into the late group.Recipients were also stratified into cohorts depending on MPT,i.e.,short(<8 hours),medium(8-16 hours)and long(>16 hours).RESULTS NMPP operational parameters were not predictive of EAD,L-GrAFT7 or 90-day outcomes.The early group had significantly less MPT and cold ischemia time than the late group(553 minutes vs 850 minutes,P<0.001)and(127.5 minutes vs 154 minutes,P=0.025),respectively.MPT had no impact in either group.CONCLUSION Increased MPT of DCD liver grafts had no adverse recipient results for the times utilized in this population,indicating its upper limits,likely beyond 24 hours,are not demonstrated within this study.Future studies are necessary to determine whether longer MPT is beneficial or detrimental to graft function and,if the latter,what is the maximum safe duration.Further studies of the effect of normothermic machine perfusion pump duration on long-term outcomes are also needed.展开更多
Optical coherence tomography angiography(OCTA)is a non-invasive imaging technique that analyzes the microvascular system of the eye.By capturing high-speed,repeated scans to detect the movement of red blood cells,OCTA...Optical coherence tomography angiography(OCTA)is a non-invasive imaging technique that analyzes the microvascular system of the eye.By capturing high-speed,repeated scans to detect the movement of red blood cells,OCTA visualizes the vascular network,revealing ischemia and reperfusion patterns in retinal vascular diseases.It has become a primary tool for assessing changes in the multilayer microvascular structure of the retina,applicable in conditions such as diabetic retinopathy,age-related macular degeneration,central serous chorioretinopathy,vascular occlusions,and glaucomatous optic neuropathy,among others.Moreover,OCTA is useful in the assessment of central nervous system diseases and is increasingly utilized in routine health examinations and scientific research.Its main advantages include high resolution,rapid,non-invasive scanning,and the ability to analyze microcirculation by observing different vascular layers through tomographic imaging.However,its sensitivity to blood flow velocity and susceptibility to artifacts,such as slow blood flow appearing as non-perfusion,are notable limitations.Overall,OCTA provides a visually intuitive approach for observing retinal blood flow and has significant clinical implications for ocular conditions.展开更多
Conventional echocardiography can sometimes pose a challenge to diagnosis due to sub-optimal images.Ultrasound contrast agents(UCAs)have been shown to drastically enhance imaging quality,particularly depicting the lef...Conventional echocardiography can sometimes pose a challenge to diagnosis due to sub-optimal images.Ultrasound contrast agents(UCAs)have been shown to drastically enhance imaging quality,particularly depicting the left ventricular endocardial borders.Their use during echocardiography has become a valuable tool in non-invasive diagnostics.UCAs provide higher-quality images that may ultimately reduce the length of hospital stays and improve patient care.The higher cost associated with UCAs in many situations has been an impediment to frequent use.However,when used as an initial diagnostic test,UCA during rest echocardiogram is more cost-effective than the traditional diagnostic approach,which frequently includes multiple tests and imaging studies to make an accurate diagnosis.They can be easily performed across multiple patient settings and provide optimal images that allow clinicians to make sound medical decisions.This consequently allows for better diagnostic accuracies and improvement in patient care.展开更多
Cardiac tissue engineering aims to efficiently replace or repair injured heart tissue using scaffolds,relevant cells,or their combination.While the combination of scaffolds and relevant cells holds the potential to ra...Cardiac tissue engineering aims to efficiently replace or repair injured heart tissue using scaffolds,relevant cells,or their combination.While the combination of scaffolds and relevant cells holds the potential to rapidly remuscularize the heart,thereby avoiding the slow process of cell recruitment,the proper ex vivo cellularization of a scaffold poses a substantial challenge.First,proper diffusion of nutrients and oxygen should be provided to the cell-seeded scaffold.Second,to generate a functional tissue construct,cells can benefit from physiological-like conditions.To meet these challenges,we developed a modular bioreactor for the dynamic cellularization of full-thickness cardiac scaffolds under synchronized mechanical and electrical stimuli.In this unique bioreactor system,we designed a cyclic mechanical load that mimics the left ventricle volume inflation,thus achieving a steady stimulus,as well as an electrical stimulus with an action potential profile to mirror the cells’microenvironment and electrical stimuli in the heart.These mechanical and electrical stimuli were synchronized according to cardiac physiology and regulated by constant feedback.When applied to a seeded thick porcine cardiac extracellular matrix(pcECM)scaffold,these stimuli improved the proliferation of mesenchymal stem/stromal cells(MSCs)and induced the formation of a dense tissue-like structure near the scaffold’s surface.Most importantly,after 35 d of cultivation,the MSCs presented the early cardiac progenitor markers Connexin-43 andα-actinin,which were absent in the control cells.Overall,this research developed a new bioreactor system for cellularizing cardiac scaffolds under cardiac-like conditions,aiming to restore a sustainable dynamic living tissue that can bear the essential cardiac excitation–contraction coupling.展开更多
Impedance pneumography has a significant advantage for continuous and noninvasive monitoring of respiration,compared with conventional flowmeter-based ventilation measurement technologies.While thoracic impedance is s...Impedance pneumography has a significant advantage for continuous and noninvasive monitoring of respiration,compared with conventional flowmeter-based ventilation measurement technologies.While thoracic impedance is sensitive to pulmonary ventilation,it is also sensitive to physiological activities such as blood flow and cardiomotility,in addition,body movement/posture.This paper explores the possibility of simultaneously monitoring pulmonary ventilation,blood circulation and cardiomotility by bioimpedance measurement.Respiratory,blood perfusion and cardiomotility signals are extracted using the wavelet method from thoracic impedance data measured in breath-holding and tidal breathing statuses,to investigate signal strength and their dependency.This research provides a foundation for the development of bedside devices to monitor various physiological activities.展开更多
基金Supported by The National Natural Science Foundation of China,No.30873464the Research Foundation from Ministry of Education of China,No.108019the Natural Science Foundation of Beijing,China,No.7132150
文摘AIM:To investigate the effects of diammonium glycyrrhizinate(Gly)on portal hypertension(PHT)in isolated portal perfused rat liver(IPPRL)with carbon tetrachloride(CCl4)-induced chronic hepatitis.METHODS:PHT model was replicated with CCl4 in rats for 84 d.Model was identified by measuring the ascetic amounts,hepatic function,portal pressure in vivo,splenic index,and pathological alterations.Inducible nitric oxide synthase(iNOS)in liver was assessed by immunohistochemistry.IPPRLs were performed at d0,d28,d56,and d84.After phenylephrine-induced constriction,Gly was geometrically used to reduce PHT.Gly action was expressed as median effective concentration(EC50)and area under the curve(AUC).Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads.RESULTS:PHT model was confirmed with ascites,splenomegaly,serum biomarkers of hepatic injury,and elevated portal pressure.Pathological findings had shown normal hepatic structure at d0,degenerations at d28,fibrosis at d56,cirrhosis at d84in PHT rats.Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development.Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis.Gly potencies were increased gradually along with PHT development,characterized with its EC50at 2.80×10-10,3.03×10-11,3.77×10-11and 4.65×10-11mol/L at d0,d28,d56and d84,respectively.Existed iNOS was located at hepatocyte at d0,stellate cells at d28,stellate cells and macrophages at d56,and macrophages in portal triads at d84.Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development.AUC values of Gly were positively correlated with existed iNOS levels in portal triads.CONCLUSION:Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis.The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads.
文摘<Abstract>Effects of amniotic fluid embolism-like plasma (AFEP) on the isolated perfused rabbit lungs (IPRL)were studied. It was found that AFEP could induce elevation of pulmonary artery pressure (PAP) and development of lung edema, which could be partially prevented by ibuprofen, a cycloxygenase inhibit0r, but amniotic fluid itself could not cause elevation of PAP and lung edema. The result suggests that AFEP-induced mediator from whole blood cells may be the important factor resulting in above-mentioned pathological changes.
基金funded by the American Heart Association Scientist Development Grant SDG12050083National Institutes of Health grant R21 HL102773
文摘Introduction:3D bio-printing technology<sup>[1-3]</sup>（Figure 1）capable of dispensing live cells,soluble factors,and phase-changing hydrogel in a desired pattern,has great potential in creating 3D tissue.However,maintaining the viability of a thick tissue structure during tissue growth and maturation is challenging due to lack of adequate vascular perfusion.In a simple tissue model with
基金Supported by JSPS KAKENHI Grant,No.JP17K10503(to Matsuno N)and JP20K11539(to Bochimoto H).
文摘BACKGROUND The machine perfusion(MP)preservation including hypothermic MP(HMP)and midthermic MP(MMP)has been considered as a promising strategy to preserve the functions of liver donated after cardiac death.The importance of understanding liver sinusoidal endothelial cells(LSEC)damage in regulating liver injury during MP has been emphasized.However,the ultrastructural changes in the LSEC and sinusoids around them after MP are unclear.AIM To investigate the ultrastructural changes in the LSEC and sinusoids around them after MP.METHODS Porcine liver grafts undergo a warm ischemia time of 60 minutes perfused for 4 h with modified University of Wisconsin gluconate solution.Group A grafts were preserved with HMP at 8℃ constantly for 4 h.Group B grafts were preserved with a rewarming solution at 22℃ by MMP for 4 h.Then the ultrastructural changes in the LSEC and sinusoids in Group A and B were comparatively analyzed by using osmium-maceration scanning electron microscopy with complementary transmission electron microscopy methods.RESULTS An analysis of the LSEC after warm ischemia revealed that mitochondria with condensed-shaped cristae,abnormal vesicles,reduction of ribosomes and the endoplasmic reticulum(ER)surround the mitochondria appeared.The MP subsequent after warm ischemia alleviate the abnormal vesicles and reduction of ribosomes in LSEC,which indicated the reduction of the ER damage.However,MMP could restore the tubular mitochondrial cristae,while after HMP the condensed and narrow mitochondrial cristae remained.In addition,the volume of the sinusoidal space in the liver grafts after MMP were restored,which indicated a lower risk of pressure injury than HMP.CONCLUSION MMP alleviates the ER damage of LSEC by warm ischemia,additionally restore the metabolism of LSEC via the normalization of mitochondria and prevent the share stress damage of liver grafts.
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 partly by the National Natural Science Foundation of China,No.82071332the Chongqing Natural Science Foundation Joint Fund for Innovation and Development,No.CSTB2023NSCQ-LZX0041 (both to ZG)。
文摘Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.
基金supported by a grant from the Guangdong Provincial Key Laboratory of Organ Donation and Transplantation Immunity (K0230015)。
文摘Ischemia-reperfusion injury (IRI) is an inherent issue in organ transplantation. Because of the allograft shortage, more and more extended criteria donor (ECD) organs are used, unfortunately these grafts are more susceptible to IRI. Although machine perfusion technology has brought hope to alleviate IRI, this technology is still unable to eradicate IRI-related organ damage. Ischemia-free liver transplantation (IFLT)can completely avoid IRI, thereby improve graft function and recipient outcome, and allow to expand organ pool. This review summarized the latest progresses in IFLT, and speculated the future development of this concept.
基金Supported by Government Assignment,No.1023022600020-6RSF Grant,No.24-15-00549Ministry of Science and Higher Education of the Russian Federation within the Framework of State Support for the Creation and Development of World-Class Research Center,No.075-15-2022-304.
文摘BACKGROUND Ischemic heart disease(IHD)impacts the quality of life and has the highest mortality rate of cardiovascular diseases globally.AIM To compare variations in the parameters of the single-lead electrocardiogram(ECG)during resting conditions and physical exertion in individuals diagnosed with IHD and those without the condition using vasodilator-induced stress computed tomography(CT)myocardial perfusion imaging as the diagnostic reference standard.METHODS This single center observational study included 80 participants.The participants were aged≥40 years and given an informed written consent to participate in the study.Both groups,G1(n=31)with and G2(n=49)without post stress induced myocardial perfusion defect,passed cardiologist consultation,anthropometric measurements,blood pressure and pulse rate measurement,echocardiography,cardio-ankle vascular index,bicycle ergometry,recording 3-min single-lead ECG(Cardio-Qvark)before and just after bicycle ergometry followed by performing CT myocardial perfusion.The LASSO regression with nested cross-validation was used to find the association between Cardio-Qvark parameters and the existence of the perfusion defect.Statistical processing was performed with the R programming language v4.2,Python v.3.10[^R],and Statistica 12 program.RESULTS Bicycle ergometry yielded an area under the receiver operating characteristic curve of 50.7%[95%confidence interval(CI):0.388-0.625],specificity of 53.1%(95%CI:0.392-0.673),and sensitivity of 48.4%(95%CI:0.306-0.657).In contrast,the Cardio-Qvark test performed notably better with an area under the receiver operating characteristic curve of 67%(95%CI:0.530-0.801),specificity of 75.5%(95%CI:0.628-0.88),and sensitivity of 51.6%(95%CI:0.333-0.695).CONCLUSION The single-lead ECG has a relatively higher diagnostic accuracy compared with bicycle ergometry by using machine learning models,but the difference was not statistically significant.However,further investigations are required to uncover the hidden capabilities of single-lead ECG in IHD diagnosis.
基金supported by National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award number R21NS114763US Army Medical Research and Materiel Command (USAMRMC) under award#W81XWH-18-1-0773merit-based career enhancement award at the Feinstein Institutes for Medical Research (to CL)
文摘Bioelectronic interventions,specifically trigeminal nerve st imulat ion(TNS),have attracted considerable attention in conditions where cortical spreading depolarizations(CSDs)accompanied by compromised cerebral perfusion may exacerbate neurological damage.While pharmacological interventions have demonstrated initial potential in addressing CSDs,a standardized treatment approach has not yet been established.The objective of this perspective is to explore emerging bioelectronic methodologies for addressing CSDs,particularly emphasizing TNS,and to underscore TNS’s capacity to enhance neurovascular coupling and cerebral perfusion.
文摘Temperature as an indicator of tissue response is widely used in clinical applications. In view of above a problem of temperature distribution in peripheral regions of extended spherical organs of a human body like, human breast involving uniformly perfused tumor is investigated in this paper. The human breast is assumed to be spherical in shape with upper hemisphere projecting out from the trunk of the body and lower hemisphere is considered to be a part of the body core. The outer surface of the breast is assumed to be exposed to the environment from where the heat loss takes place by conduction, convection, radiation and evaporation. The heat transfer from core to the surface takes place by thermal conduction and blood perfusion. Also metabolic activity takes place at different rates in different layers of the breast. An elliptical-shaped tumor is assumed to be present in the dermis region of human breast. A finite element model is developed for a two-dimensional steady state case incorporating the important parameters like blood flow, metabolic activity and thermal conductivity. The triangular ring elements are employed to discretize the region. Appropriate boundary conditions are framed using biophysical conditions. The numerical results are used to study the effect of tumor on temperature distribution in the region.
文摘Myocardial ischemia is the most common and primary cause of myocardium damage. Numerous conventional techniques and methods have been developed for ischemia and reperfusion studies. However, because of damage to the heart sample, most of these techniques can not be used to continuously monitor the full dynamic course of the myocardial metabolic pathway. The nuclear magnetic resonnance (NMR) surface coil technique, which overcomes the limitations of conventional instrumentation, can be used to quantitatively study every stage of the perfused heart (especially after perfusion stoppage) continuously, dynamically, and without damage under normal or designed physiological conditions at the molecular level. In this paper, 31 P NMR was used to study the effects of ischemia and hypoxia on isolated perfused hearts. The results show that complete hypoxia caused more severe functional damage to the myocardial cells than complete ischemia.
文摘Post-reperfusion syndrome(PRS)in liver transplant recipients remains one of the most dreaded complications in liver transplant surgery.PRS can impact the short-term and long-term patient and graft outcomes.The definition of PRS has evolved over the years,from changes in arterial blood pressures and heart and/or de-creases in the systemic vascular resistance and cardiac output to including the fibrinolysis and grading the severity of PRS.However,all that did not reflect on the management of PRS or its impact on the outcomes.In recent years,new scientific techniques and new technology have been in the pipeline to better understand,manage and maybe prevent PRS.These new methods and techniques are still in the infancy,and they have to be proven not in prevention and management of PRS but their effects in the patient and graft outcomes.In this article,we will review the long history of PRS,its definition,etiology,mana-gement and most importantly the new advances in science and technology to prevent and properly manage PRS.
基金Supported by The Jewel and Frank Benson Family Endowmentand The Jewel and Frank Benson Research Professorship.
文摘BACKGROUND Traditional limitations of cold static storage(CSS)on ice at 4℃during lung transplantation have necessitated limiting cold ischemic time(CIT)to 4-6 hours.Ex vivo lung perfusion(EVLP)can extend this preservation time through the suspension of CIT and normothermic perfusion.As we continue to further expand the donor pool in all aspects of lung transplantation,teams are frequently traveling further distances to procure organs.AIM To determine the effect of CSS or EVLP on donors with extended travel distance[>750 nautical miles(NM)]to recipient.METHODS Lung transplants,whose donor traveled greater than 750 NM,were identified from the United Network for Organ Sharing Database.Recipients were stratified into either:CSS or EVLP,based on preservation method.Groups were assessed with comparative statistics and survival was assessed by Kaplan-Meier methods.A 3:1 propensity match was then created,and same analysis was repeated.RESULTS Prior to matching,those in the EVLP group had significantly increased postoperative morbidity to include dialysis,ventilator use,acute rejection,and treated rejection in the first year(P<0.05 for all).However,there were no significant differences in midterm survival(P=0.18).Following matching,those in the EVLP group again had significantly increased post-operative morbidity to include dialysis,extracorporeal membrane oxygenation use,ventilator use,and treated rejection in the first year(P<0.05 for all).As before,there were no significant differences in midterm survival following matching(P=0.08).CONCLUSION While there was no significant difference in survival,EVLP patients had increased peri-operative morbidity.With the advent of changes in CSS with 10℃storage further analysis is necessary to evaluate the best methods for utilizing organs from increased distances.
文摘BACKGROUND Liver transplantation(LT)is the only curative,life-saving option for children and adults with end-stage liver disease.Due to the well-known shortage and heterogeneity of grafts,split LT(SLT)is an attractive strategy to expand the donor pool and reduce waitlist times.Given increased risk of cold ischemia time with SLT,machine perfusion represents a promising option to reduce it and optimize transplant logistics and outcomes.The present communication describes various possible combinations of procurement steps to perform SLT facilitated by placing one or both grafts on a normothermic machine perfusion(NMP)closed circuit device.CASE SUMMARY A 19-month-old female with biliary atresia after failed Kasai portoenterostomy and a 42-year-old woman with unresectable intrahepatic cholangiocarcinoma were selected as recipients for a SLT from a 17-year-old male donor.The SLT generated a left lateral segment and a right trisectional graft of appropriate volume for both recipients.After a mixed in-situ and ex-situ split,in order to improve logistics,the right trisectional graft was placed on a closed circuit NMP device,following an appropriate vascular reconstruction.Both grafts were implanted with excellent short-term outcomes.CONCLUSION Use of NMP with SLT for preservation prior to implantation allows not only for graft optimization but also for significant improvement of transplant logistics.We propose various models and standardization of logistic options for combining SLT with NMP to optimize graft availability and outcomes.
基金Supported by Science and Technology Program of Guangzhou,No.2024A03J1029Science and Technology Program of Chinese Medicine and Integrated Chinese and Western Medicine in Guangzhou,No.20252A010001.
文摘BACKGROUND Contrast-enhanced ultrasonography(CEUS)is utilized to assess the therapeutic efficacy of interventional therapy in liver cancer patients,offering insights into tumor blood flow changes,angiogenesis,and tumor markers.AIM To evaluate the use of CEUS in examining the effectiveness of interventional therapy for liver cancer,we aim to investigate its diagnostic utility for tumor perfusion patterns,microvessel density,perfusion recovery,blood flow enhancement response,and alterations in tumor markers among patients receiving interventional therapy for liver cancer.METHODS The study involved 124 patients who underwent interventional therapy for liver cancer at Guangzhou First People’s Hospital from January 2022 to February 2024.All patients were examined using CEUS before treatment and at 1 month,3 months,and 6 months,and the concentrations of tumor markers were collected and statistically analyzed using Statistical Package for the Social Sciences 25.0.Receiver operating characteristic(ROC)curves were used to evaluate the diagnostic efficacy of CEUS and analyze its sensitivity,specificity,and correlation with clinical indicators.RESULTS Before treatment,tumor blood flow was primarily enhanced.After treatment,enhanced perfusion declined,while uniform and non-uniform perfusion increased,indicating reduced tumor activity.Enhanced perfusion decreased from 68.25%before treatment to 53.75%at 6 months post-treatment(F=6.123,P=0.016),indicating reduced tumor activity.The microvessel density of the tumors decreased significantly after treatment(P<0.05),and the proportion of low microvessel density increased.After treatment,perfusion recovery in the tumor area improved,the proportion of complete and partial responses gradually increased,and the proportion of stable lesions decreased(P<0.05).The levels of alphafetoprotein,carcinoembryonic antigen,and carbohydrate antigen 19-9 decreased by 68.7%,30.4%,and 41.6%,respectively,at 6 months post-treatment(P<0.05).CEUS showed a sensitivity of 85.72%,specificity of 92.31%,and area under the curve of 0.911(95%CI:0.883–0.939)for evaluating treatment response.ROC curve analysis showed that CEUS had high sensitivity and specificity and could effectively evaluate the efficacy of interventional therapy for liver cancer.CONCLUSION CEUS has high diagnostic value in evaluating therapeutic effects in patients with liver cancer following interventional therapy.It can reflect changes in tumor blood flow,angiogenesis,and tumor marker levels,providing an effective basis for real-time monitoring of treatment outcomes.
文摘BACKGROUND The normothermic machine perfusion pump(NMPP)could shape the future of transplantation.Providing ex-vivo optimization,NMPP attenuates ischemic insult while replenishing energy.An understanding of machine perfusion time(MPT)impact and potential clinical benefits is paramount and necessitates exploration.AIM To investigate the relationship between MPT and post-transplant graft function.METHODS Retrospective review of the first 50 donation after circulatory death(DCD)grafts preserved using NMPP in a tertiary institution was performed.Essential preser-vation time points,graft parameters,recipient information,and postoperative outcomes were prospectively recorded.Early allograft dysfunction(EAD),L-Graft7 score and 90-day outcomes were collected for all grafts.The first 20 re-cipients were allocated into the early group,considered the learning curve population for the center.The subsequent 30 were allocated into the late group.Recipients were also stratified into cohorts depending on MPT,i.e.,short(<8 hours),medium(8-16 hours)and long(>16 hours).RESULTS NMPP operational parameters were not predictive of EAD,L-GrAFT7 or 90-day outcomes.The early group had significantly less MPT and cold ischemia time than the late group(553 minutes vs 850 minutes,P<0.001)and(127.5 minutes vs 154 minutes,P=0.025),respectively.MPT had no impact in either group.CONCLUSION Increased MPT of DCD liver grafts had no adverse recipient results for the times utilized in this population,indicating its upper limits,likely beyond 24 hours,are not demonstrated within this study.Future studies are necessary to determine whether longer MPT is beneficial or detrimental to graft function and,if the latter,what is the maximum safe duration.Further studies of the effect of normothermic machine perfusion pump duration on long-term outcomes are also needed.
文摘Optical coherence tomography angiography(OCTA)is a non-invasive imaging technique that analyzes the microvascular system of the eye.By capturing high-speed,repeated scans to detect the movement of red blood cells,OCTA visualizes the vascular network,revealing ischemia and reperfusion patterns in retinal vascular diseases.It has become a primary tool for assessing changes in the multilayer microvascular structure of the retina,applicable in conditions such as diabetic retinopathy,age-related macular degeneration,central serous chorioretinopathy,vascular occlusions,and glaucomatous optic neuropathy,among others.Moreover,OCTA is useful in the assessment of central nervous system diseases and is increasingly utilized in routine health examinations and scientific research.Its main advantages include high resolution,rapid,non-invasive scanning,and the ability to analyze microcirculation by observing different vascular layers through tomographic imaging.However,its sensitivity to blood flow velocity and susceptibility to artifacts,such as slow blood flow appearing as non-perfusion,are notable limitations.Overall,OCTA provides a visually intuitive approach for observing retinal blood flow and has significant clinical implications for ocular conditions.
文摘Conventional echocardiography can sometimes pose a challenge to diagnosis due to sub-optimal images.Ultrasound contrast agents(UCAs)have been shown to drastically enhance imaging quality,particularly depicting the left ventricular endocardial borders.Their use during echocardiography has become a valuable tool in non-invasive diagnostics.UCAs provide higher-quality images that may ultimately reduce the length of hospital stays and improve patient care.The higher cost associated with UCAs in many situations has been an impediment to frequent use.However,when used as an initial diagnostic test,UCA during rest echocardiogram is more cost-effective than the traditional diagnostic approach,which frequently includes multiple tests and imaging studies to make an accurate diagnosis.They can be easily performed across multiple patient settings and provide optimal images that allow clinicians to make sound medical decisions.This consequently allows for better diagnostic accuracies and improvement in patient care.
基金funded by the Israeli Ministry of Innovation,Science and Technology(Grant No.3-11873)the Israel Science Foundation(Grant No.1563/10)+1 种基金the Randy L.and Melvin R.Berlin Family Research Center for Regenerative Medicinethe Gurwin Family Foundation.
文摘Cardiac tissue engineering aims to efficiently replace or repair injured heart tissue using scaffolds,relevant cells,or their combination.While the combination of scaffolds and relevant cells holds the potential to rapidly remuscularize the heart,thereby avoiding the slow process of cell recruitment,the proper ex vivo cellularization of a scaffold poses a substantial challenge.First,proper diffusion of nutrients and oxygen should be provided to the cell-seeded scaffold.Second,to generate a functional tissue construct,cells can benefit from physiological-like conditions.To meet these challenges,we developed a modular bioreactor for the dynamic cellularization of full-thickness cardiac scaffolds under synchronized mechanical and electrical stimuli.In this unique bioreactor system,we designed a cyclic mechanical load that mimics the left ventricle volume inflation,thus achieving a steady stimulus,as well as an electrical stimulus with an action potential profile to mirror the cells’microenvironment and electrical stimuli in the heart.These mechanical and electrical stimuli were synchronized according to cardiac physiology and regulated by constant feedback.When applied to a seeded thick porcine cardiac extracellular matrix(pcECM)scaffold,these stimuli improved the proliferation of mesenchymal stem/stromal cells(MSCs)and induced the formation of a dense tissue-like structure near the scaffold’s surface.Most importantly,after 35 d of cultivation,the MSCs presented the early cardiac progenitor markers Connexin-43 andα-actinin,which were absent in the control cells.Overall,this research developed a new bioreactor system for cellularizing cardiac scaffolds under cardiac-like conditions,aiming to restore a sustainable dynamic living tissue that can bear the essential cardiac excitation–contraction coupling.
基金the National Natural Science Foundation of China(No.61371017)the Interdisciplinary Program of Shanghai Jiao Tong University(No.YG2021QN37)。
文摘Impedance pneumography has a significant advantage for continuous and noninvasive monitoring of respiration,compared with conventional flowmeter-based ventilation measurement technologies.While thoracic impedance is sensitive to pulmonary ventilation,it is also sensitive to physiological activities such as blood flow and cardiomotility,in addition,body movement/posture.This paper explores the possibility of simultaneously monitoring pulmonary ventilation,blood circulation and cardiomotility by bioimpedance measurement.Respiratory,blood perfusion and cardiomotility signals are extracted using the wavelet method from thoracic impedance data measured in breath-holding and tidal breathing statuses,to investigate signal strength and their dependency.This research provides a foundation for the development of bedside devices to monitor various physiological activities.
