It has shown that altering crosslink density of biopolymers will regulate the morphology of Mesenchymal Stem Cells （MSCs） and the subsequent MSCs differentia- tion. These observations have been found in a wide range...It has shown that altering crosslink density of biopolymers will regulate the morphology of Mesenchymal Stem Cells （MSCs） and the subsequent MSCs differentia- tion. These observations have been found in a wide range of biopolymers. However, a recent work published in Nature Materials has revealed that MSCs morphology and differen- tiation was unaffected by crosslink density of polydimethyl- siloxane （PDMS）, which remains elusive. To understand such unusual behaviour, we use nanoindentation tests and modelling to characterize viscoelastic properties and sur- face adhesion of PDMS with different base：crosslink ratio varied from 50：1 （50D） to 10：1 （10D）. It has shown that lower crosslink density leads to lower elastic moduli. De- spite lower nanoindentation elastic moduli, PDMS with lowest crosslink density has higher local surface adhesion which would affect cell-biomaterials interactions. This work suggests that surface adhesion is likely another important physical cue to regulate cell-biomaterials interactions.展开更多
Background: The US FDA has recently approved autologous cultured fibroblast cells (ACF) as treatment for cutaneous contour defects. ACF provides an alternative to synthetic fillers or fat grafting with the significant...Background: The US FDA has recently approved autologous cultured fibroblast cells (ACF) as treatment for cutaneous contour defects. ACF provides an alternative to synthetic fillers or fat grafting with the significant advantage of producing longer lasting effect. Methods: This was a prospective open label single group clinical study to demonstrate the clinical efficacy of ACF that we have replicated in our lab. The study enrolled 18 patients with nasolabial folds from 2 centres in Malaysia in 2011-2012. ACF at dose of 23 or 92 million cells were injected on 3 occasions at 4 weeks interval. Efficacy at 6- and 12-month post treatment was assessed using a standardized 7-point scale which was performed by the 2 investigators as well as a panel of 7 independent evaluators. Results: We obtained a successful outcome (primary endpoint), defined as improvement in the appearance of the nasolabial fold of at least 2 points on the 7-point scale, in 33% of patients as assessed by investigators at 12-month follow-up and in 22% of patients assessed by independent evaluators. Investigators also found 78% of patients having had a 1-point improvement from baseline while independent evaluators found 83% of patients having improved by as much. Patients were uniformly (100%) satisfied with the improvement in their appearance. No treatment-related adverse event was reported. Baseline score and follow-up duration had significant effect on treatment response. The greater the baseline severity and the longer the post-treatment follow-up, the better the response to ACF. Larger dose of cells (92 million cells) has little additional effect suggesting that the 1 mL dose (23 million cells) is near optimal. Older patients showed a trend towards poorer response but this was not statistically significant. Conclusions: We have successfully replicated the laboratory method and clinical procedure to perform ACF treatment which was effective in improving the appearance of nasolabial folds in some patients.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 electromechnical mapping demonstrated significant improvement at three months after implantation of BMSCs compared with that pre-injection in both cardiac mechanical capability as left line local shorting [LLS, (11.29±1.64)% vs (7.32± 1.86)%, P<0.05] and electrical property as left ventricular endocardial unipolar voltage [UV, (10.38±1.12) mV vs (7.61±1.09) mV, P<0.01]; perfusion defect decreased from (36.2±6.2) % to (20.3±5.31)% (P<0.01). Twenty-four-hour electrocardiographic monitoring demonstrated no arrhythmias occurred at three-months follow-up.Conclusions The transplantation of BMSCs might improve the cardiac function and it is safe and feasible with no deaths or malignant arrhythmias.展开更多
T cell activation and tolerance are tightly regulated by costimulatory and coinhibitory molecules.B7 family members play a crucial role in regulating immune responses.In this study,we identified erythroid membrane-ass...T cell activation and tolerance are tightly regulated by costimulatory and coinhibitory molecules.B7 family members play a crucial role in regulating immune responses.In this study,we identified erythroid membrane-associated protein(ERMAP)as a novel T cell inhibitory molecule.ERMAP shares significant sequence and structural homology with existing B7 family members in its extracellular domain.The ERMAP protein is expressed on the cell surface of resting and activated antigen-presenting cells(APCs)and in some tumor tissues.The putative ERMAP receptor is expressed on activated CD4 and CD8 T cells and macrophages.Both mouse and human ERMAP-IgG2a Fc(ERMAP-Ig)fusion proteins inhibit T cell functions in vitro.Administration of ERMAP-Ig protein ameliorates autoimmune diseases,including experimental autoimmune encephalomyelitis and type 1 diabetes,in mice.Anti-ERMAP antibody enhances macrophage phagocytosis of cancer cells in vitro.Furthermore,administration of an anti-ERMAP antibody inhibits tumor growth in mice likely by blocking the inhibitory effects of ERMAP on T cells and macrophages.Our results suggest that therapeutic interaction with the ERMAP inhibitory pathway may represent a novel strategy for treating patients with autoimmune disease or cancer.展开更多
基金funded by EPSRC–Newcastle University Sandpit Workshop Award
文摘It has shown that altering crosslink density of biopolymers will regulate the morphology of Mesenchymal Stem Cells （MSCs） and the subsequent MSCs differentia- tion. These observations have been found in a wide range of biopolymers. However, a recent work published in Nature Materials has revealed that MSCs morphology and differen- tiation was unaffected by crosslink density of polydimethyl- siloxane （PDMS）, which remains elusive. To understand such unusual behaviour, we use nanoindentation tests and modelling to characterize viscoelastic properties and sur- face adhesion of PDMS with different base：crosslink ratio varied from 50：1 （50D） to 10：1 （10D）. It has shown that lower crosslink density leads to lower elastic moduli. De- spite lower nanoindentation elastic moduli, PDMS with lowest crosslink density has higher local surface adhesion which would affect cell-biomaterials interactions. This work suggests that surface adhesion is likely another important physical cue to regulate cell-biomaterials interactions.
文摘Background: The US FDA has recently approved autologous cultured fibroblast cells (ACF) as treatment for cutaneous contour defects. ACF provides an alternative to synthetic fillers or fat grafting with the significant advantage of producing longer lasting effect. Methods: This was a prospective open label single group clinical study to demonstrate the clinical efficacy of ACF that we have replicated in our lab. The study enrolled 18 patients with nasolabial folds from 2 centres in Malaysia in 2011-2012. ACF at dose of 23 or 92 million cells were injected on 3 occasions at 4 weeks interval. Efficacy at 6- and 12-month post treatment was assessed using a standardized 7-point scale which was performed by the 2 investigators as well as a panel of 7 independent evaluators. Results: We obtained a successful outcome (primary endpoint), defined as improvement in the appearance of the nasolabial fold of at least 2 points on the 7-point scale, in 33% of patients as assessed by investigators at 12-month follow-up and in 22% of patients assessed by independent evaluators. Investigators also found 78% of patients having had a 1-point improvement from baseline while independent evaluators found 83% of patients having improved by as much. Patients were uniformly (100%) satisfied with the improvement in their appearance. No treatment-related adverse event was reported. Baseline score and follow-up duration had significant effect on treatment response. The greater the baseline severity and the longer the post-treatment follow-up, the better the response to ACF. Larger dose of cells (92 million cells) has little additional effect suggesting that the 1 mL dose (23 million cells) is near optimal. Older patients showed a trend towards poorer response but this was not statistically significant. Conclusions: We have successfully replicated the laboratory method and clinical procedure to perform ACF treatment which was effective in improving the appearance of nasolabial folds in some patients.
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 electromechnical mapping demonstrated significant improvement at three months after implantation of BMSCs compared with that pre-injection in both cardiac mechanical capability as left line local shorting [LLS, (11.29±1.64)% vs (7.32± 1.86)%, P<0.05] and electrical property as left ventricular endocardial unipolar voltage [UV, (10.38±1.12) mV vs (7.61±1.09) mV, P<0.01]; perfusion defect decreased from (36.2±6.2) % to (20.3±5.31)% (P<0.01). Twenty-four-hour electrocardiographic monitoring demonstrated no arrhythmias occurred at three-months follow-up.Conclusions The transplantation of BMSCs might improve the cardiac function and it is safe and feasible with no deaths or malignant arrhythmias.
基金This work was supported by grants from the NIH(1R01AI123131–01)the Connecticut Regenerative Medicine Research Fund(16-RMB-UCONN-02).
文摘T cell activation and tolerance are tightly regulated by costimulatory and coinhibitory molecules.B7 family members play a crucial role in regulating immune responses.In this study,we identified erythroid membrane-associated protein(ERMAP)as a novel T cell inhibitory molecule.ERMAP shares significant sequence and structural homology with existing B7 family members in its extracellular domain.The ERMAP protein is expressed on the cell surface of resting and activated antigen-presenting cells(APCs)and in some tumor tissues.The putative ERMAP receptor is expressed on activated CD4 and CD8 T cells and macrophages.Both mouse and human ERMAP-IgG2a Fc(ERMAP-Ig)fusion proteins inhibit T cell functions in vitro.Administration of ERMAP-Ig protein ameliorates autoimmune diseases,including experimental autoimmune encephalomyelitis and type 1 diabetes,in mice.Anti-ERMAP antibody enhances macrophage phagocytosis of cancer cells in vitro.Furthermore,administration of an anti-ERMAP antibody inhibits tumor growth in mice likely by blocking the inhibitory effects of ERMAP on T cells and macrophages.Our results suggest that therapeutic interaction with the ERMAP inhibitory pathway may represent a novel strategy for treating patients with autoimmune disease or cancer.
