Objective To compare the efficiency and safety of intracoronary transplantation of peripheral blood stem cells (PBSC) between elderly and younger patients with heart failure after myocardial infarction (MI). Methods T...Objective To compare the efficiency and safety of intracoronary transplantation of peripheral blood stem cells (PBSC) between elderly and younger patients with heart failure after myocardial infarction (MI). Methods Twenty-five patients with heart failure after MI were divided into aged group(≥60 years,n=13) and non-aged group(<60years,n=12)to receive intracoronary PBSC transplantation (PBSCT) following bone marrow cells mobilized by granulocyte colony-stimulating factor(G-CSF). Clinical data including coronary lesion characteristic, left ventricular shape,infarct region area and cardiac function, as well as adverse side effects between the two groups were compared. Left ventricular function was evaluated before and 6 months after the treatment by single photon emission computed tomography(SPECT). Results At 6 months, the left ventricular ejection fraction (LVEF) and 6 minute walk test (6MWT) distance increased, while the left ventricular diastolic diameter (LVDd) decreased significantly in both groups. There were no significant difference between the two groups in absolute change in the cardiac function parameters. Conclusions The present study demonstrated that autologous intracoronary PBSCT might be safe and feasible for both old and younger patients with heart failure after MI and left ventricular function is significantly improved.(J Geriatr Cardiol 2007;4:233-237.)展开更多
BACKGROUND:Intravenous transplantation has been regarded as a most safe method in stem cell therapies.There is evidence showing the homing of bone marrow stem cells(BMSCs) into the injured sites,and thus these cells c...BACKGROUND:Intravenous transplantation has been regarded as a most safe method in stem cell therapies.There is evidence showing the homing of bone marrow stem cells(BMSCs) into the injured sites,and thus these cells can be used in the treatment of acute myocardial infarction(Ml).This study aimed to investigate the effect of intravenous and epicardial transplantion of BMSCs on myocardial infarction size in a rabbit model.METHODS:A total of 60 New Zealand rabbits were randomly divided into three groups:control group,epicardium group(group Ⅰ) and ear vein group(group Ⅱ).The BMSCs were collected from the tibial plateau in group Ⅰ and group Ⅱ,cultured and labeled.In the three groups,rabbits underwent thoracotomy and ligation of the middle left anterior descending artery.The elevation of ST segment>0.2 mV lasting for 30 minutes on the lead Ⅱ and Ⅲ of electrocardiogram suggested successful introduction of myocardial infarction.Two weeks after myocardial infarction,rabbits in group Ⅰ were treated with autogenous BMSCs at the infarct region and those in group Ⅱ received intravenous transplantation of BMSCs.In the control group,rabbits were treated with PBS following thoracotomy.Four weeks after myocardial infarction,the heart was collected from all rabbits and the infarct size was calculated.The heart was cut into sections followed by HE staining and calculation of infarct size with an image system.RESULTS:In groups Ⅰ and Ⅱ,the infarct size was significantly reduced after transplantation with BMSCs when compared with the control group(P<0.05).However,there was no significant difference in the infarct size between groups Ⅰ and Ⅱ(P>0.05).CONCLUSION:Transplantation of BMSCs has therapeutic effect on Ml.Moreover,epicardial and intravenous transplantation of BMSCs has comparable therapeutic efficacy on myocardial infarction.展开更多
Advances in stem cell science and potential clinical applications have brought clinical medicine closer to the actualization of Regenerative Medicine—an extension of transplantation of organs and cells and implantati...Advances in stem cell science and potential clinical applications have brought clinical medicine closer to the actualization of Regenerative Medicine—an extension of transplantation of organs and cells and implantation of bioprosthetics and biodevices. The goal of such therapeutics will be intervention prior to onset of severe individual disability, enhance organ function and enhance patient performance status without incurring the economic impacts of standard organ transplantation. Regenerative Medicine is already demonstrating proof of principle or efficacy in restora- tion of myocardial contractility, joint mobility and function, immune competence, pulmonary function, immunologic self- tolerance, motor function and normal hemoglobin production with the next targets—diabetes mellitus (type I and type II), neurologic injury, hepatic dysfunction preparing to enter trials. Expenditures on health care needs of an aging U.S. citizenry approximate 20-25% ($3 trillion) of U.S. GDP currently and may to grow to 40% of U.S. GDP by 2025. As the potential of Regenerative Medicine is clinically realized, the societal impact and economic benefits will be disproportionately magnified in the economies of industrialized nations. The experi- ence of the Department of Health and Human Services (HHS), United Network for Organ Sharing (UNOS), the National Bone Marrow Donor Registry (NBMDR), and the National Vaccine Injury Compensation Programs (NVICP) can help ensure that as Regenerative Medicine strives to achieve clinical benefits while avoiding decimation of therapeutic options by product liability and medical malpractice concerns—concerns that crippled the U.S. vaccine manufacturing industry until the creation of the NVICP. The first 50 years of organ/cell/tissue transplantation demonstrates that clinical reality of allogeneic and autologous transplantation can antedate complete understanding of the basic science underlying successful transplantation. Product liability and medical malpractice liability have not impeded the development and growth of organ/cell/tissue transplanta- tion despite increased risks of infection, malignancy and cardiovascular disease in transplant recipients. Currently, human transplantation is only performed using FDA/CBER-approved, non-embryonic stem cells from peripheral blood, bone marrow or umbilical cord blood. Federal legislation passed in 2005 (HR2520 and S1317: The Bone Marrow and Cord Blood Cell Transplantation Program) authorizes the Secretary of Health and Human Services acting through the Director of HRSA to ensure uniform stem cell units distribution and outcomes monitoring via the federally-designated C.W. Bill Young Cell Transplant Program. Historically in the U.S., human biological therapies (vaccines, organ transplant and stem cell transplant) have re- quired federal protections to ensure continued distribution, fair access and avoidance of inhibitory product liability via protections afforded under the “stewardship” of the Secretary of Health and Human Services. The National Childhood Vaccine Injury Act of 1986 established the NVICP to equitably and expeditiously compensate individuals, or families of individuals, who have been declared injured by vaccines, thereby stabilizing a once imperiled vaccine supply by substan-tially reducing the threat of liability for vaccine companies, physicians, and other health care professionals who administer vaccines. Vaccines were the first biologics administered to U.S. citizens en masse and presage stem cell therapeutics (which may similarly be administered to millions) will similarly necessitate that a Stem Cell Injury Compensation Program (SCICP) will also need to be in place to demonstrate an intention to do good, an understanding that industry may do well, but that the health care consumer has a right of protection—all recognized from the outset. The Federal Tort Claims Act (FTCA) addresses liability claims via the Executive, Judicial and Legislative branches of Government, providing an um- brella of liability protection to other participants in the stem cell unit “chain of custody” under the FTCA—similar to the protection from product liability seen in organ and stem cell transplantation for the past 40-50 years. Efficacious development of regenerative medicine capabilities will mandate controlled access must first be provided for individuals with life-threatening diseases without therapeutic options or unable to benefit from or receive proven therapeutic options (ALS, cardiomyopathy and deemed not a candidate for heart transplantation, IDDM with hypoglyce- mic unawareness and no allogeneic source of traditional islet cell replacement available via HRSA) and mandates the prompt adoption of business and legal principles to ensure that the fate of the vaccine manufacturing industry does not become the fate of the stem cell therapeutics industry. If legal and regulatory concerns consume an increasing percentage of health care dollars that could be focused upon innovation, the Regenerative Medicine model will have not realized its full potential. The Diabetes Transplantation/Regenerative Medicine Model is the first organ to cell transplant model outside of oncology to demonstrate the regenerative medicine paradigm. Since all human tissues can be already recapitulated by human stem cells and key patent holders already exist, outlet or distribution of “more-than-minimally-manipulated stem cell units” as an IND approved under FDA/CBER guidelines can be accomplished via the current HHS/HRSA/Dept of Trans- plant methodology. As cardiovascular stem cell researchers develop human therapeutics utilizing more-than-minimally- manipulated stem cell products, they could be afforded protections from product liability historically enjoyed by the transplant community. Extending the Diabetes Transplant/Regenerative Medicine Model to the more than 5 million Americans with chronic heart failure, cell-based therapies to regenerate myocardial contractility could fill an existing void and be delivered in conjunction with and consistent with existing distribution of organs and tissues via HRSA/Department of Transplantation.展开更多
文摘Objective To compare the efficiency and safety of intracoronary transplantation of peripheral blood stem cells (PBSC) between elderly and younger patients with heart failure after myocardial infarction (MI). Methods Twenty-five patients with heart failure after MI were divided into aged group(≥60 years,n=13) and non-aged group(<60years,n=12)to receive intracoronary PBSC transplantation (PBSCT) following bone marrow cells mobilized by granulocyte colony-stimulating factor(G-CSF). Clinical data including coronary lesion characteristic, left ventricular shape,infarct region area and cardiac function, as well as adverse side effects between the two groups were compared. Left ventricular function was evaluated before and 6 months after the treatment by single photon emission computed tomography(SPECT). Results At 6 months, the left ventricular ejection fraction (LVEF) and 6 minute walk test (6MWT) distance increased, while the left ventricular diastolic diameter (LVDd) decreased significantly in both groups. There were no significant difference between the two groups in absolute change in the cardiac function parameters. Conclusions The present study demonstrated that autologous intracoronary PBSCT might be safe and feasible for both old and younger patients with heart failure after MI and left ventricular function is significantly improved.(J Geriatr Cardiol 2007;4:233-237.)
基金supported by grants from the Scientific Research Plan Project of Liaoning Province(20092250096)Scientific Research Plan Project of Dalian(2010E15SF178)
文摘BACKGROUND:Intravenous transplantation has been regarded as a most safe method in stem cell therapies.There is evidence showing the homing of bone marrow stem cells(BMSCs) into the injured sites,and thus these cells can be used in the treatment of acute myocardial infarction(Ml).This study aimed to investigate the effect of intravenous and epicardial transplantion of BMSCs on myocardial infarction size in a rabbit model.METHODS:A total of 60 New Zealand rabbits were randomly divided into three groups:control group,epicardium group(group Ⅰ) and ear vein group(group Ⅱ).The BMSCs were collected from the tibial plateau in group Ⅰ and group Ⅱ,cultured and labeled.In the three groups,rabbits underwent thoracotomy and ligation of the middle left anterior descending artery.The elevation of ST segment>0.2 mV lasting for 30 minutes on the lead Ⅱ and Ⅲ of electrocardiogram suggested successful introduction of myocardial infarction.Two weeks after myocardial infarction,rabbits in group Ⅰ were treated with autogenous BMSCs at the infarct region and those in group Ⅱ received intravenous transplantation of BMSCs.In the control group,rabbits were treated with PBS following thoracotomy.Four weeks after myocardial infarction,the heart was collected from all rabbits and the infarct size was calculated.The heart was cut into sections followed by HE staining and calculation of infarct size with an image system.RESULTS:In groups Ⅰ and Ⅱ,the infarct size was significantly reduced after transplantation with BMSCs when compared with the control group(P<0.05).However,there was no significant difference in the infarct size between groups Ⅰ and Ⅱ(P>0.05).CONCLUSION:Transplantation of BMSCs has therapeutic effect on Ml.Moreover,epicardial and intravenous transplantation of BMSCs has comparable therapeutic efficacy on myocardial infarction.
文摘Advances in stem cell science and potential clinical applications have brought clinical medicine closer to the actualization of Regenerative Medicine—an extension of transplantation of organs and cells and implantation of bioprosthetics and biodevices. The goal of such therapeutics will be intervention prior to onset of severe individual disability, enhance organ function and enhance patient performance status without incurring the economic impacts of standard organ transplantation. Regenerative Medicine is already demonstrating proof of principle or efficacy in restora- tion of myocardial contractility, joint mobility and function, immune competence, pulmonary function, immunologic self- tolerance, motor function and normal hemoglobin production with the next targets—diabetes mellitus (type I and type II), neurologic injury, hepatic dysfunction preparing to enter trials. Expenditures on health care needs of an aging U.S. citizenry approximate 20-25% ($3 trillion) of U.S. GDP currently and may to grow to 40% of U.S. GDP by 2025. As the potential of Regenerative Medicine is clinically realized, the societal impact and economic benefits will be disproportionately magnified in the economies of industrialized nations. The experi- ence of the Department of Health and Human Services (HHS), United Network for Organ Sharing (UNOS), the National Bone Marrow Donor Registry (NBMDR), and the National Vaccine Injury Compensation Programs (NVICP) can help ensure that as Regenerative Medicine strives to achieve clinical benefits while avoiding decimation of therapeutic options by product liability and medical malpractice concerns—concerns that crippled the U.S. vaccine manufacturing industry until the creation of the NVICP. The first 50 years of organ/cell/tissue transplantation demonstrates that clinical reality of allogeneic and autologous transplantation can antedate complete understanding of the basic science underlying successful transplantation. Product liability and medical malpractice liability have not impeded the development and growth of organ/cell/tissue transplanta- tion despite increased risks of infection, malignancy and cardiovascular disease in transplant recipients. Currently, human transplantation is only performed using FDA/CBER-approved, non-embryonic stem cells from peripheral blood, bone marrow or umbilical cord blood. Federal legislation passed in 2005 (HR2520 and S1317: The Bone Marrow and Cord Blood Cell Transplantation Program) authorizes the Secretary of Health and Human Services acting through the Director of HRSA to ensure uniform stem cell units distribution and outcomes monitoring via the federally-designated C.W. Bill Young Cell Transplant Program. Historically in the U.S., human biological therapies (vaccines, organ transplant and stem cell transplant) have re- quired federal protections to ensure continued distribution, fair access and avoidance of inhibitory product liability via protections afforded under the “stewardship” of the Secretary of Health and Human Services. The National Childhood Vaccine Injury Act of 1986 established the NVICP to equitably and expeditiously compensate individuals, or families of individuals, who have been declared injured by vaccines, thereby stabilizing a once imperiled vaccine supply by substan-tially reducing the threat of liability for vaccine companies, physicians, and other health care professionals who administer vaccines. Vaccines were the first biologics administered to U.S. citizens en masse and presage stem cell therapeutics (which may similarly be administered to millions) will similarly necessitate that a Stem Cell Injury Compensation Program (SCICP) will also need to be in place to demonstrate an intention to do good, an understanding that industry may do well, but that the health care consumer has a right of protection—all recognized from the outset. The Federal Tort Claims Act (FTCA) addresses liability claims via the Executive, Judicial and Legislative branches of Government, providing an um- brella of liability protection to other participants in the stem cell unit “chain of custody” under the FTCA—similar to the protection from product liability seen in organ and stem cell transplantation for the past 40-50 years. Efficacious development of regenerative medicine capabilities will mandate controlled access must first be provided for individuals with life-threatening diseases without therapeutic options or unable to benefit from or receive proven therapeutic options (ALS, cardiomyopathy and deemed not a candidate for heart transplantation, IDDM with hypoglyce- mic unawareness and no allogeneic source of traditional islet cell replacement available via HRSA) and mandates the prompt adoption of business and legal principles to ensure that the fate of the vaccine manufacturing industry does not become the fate of the stem cell therapeutics industry. If legal and regulatory concerns consume an increasing percentage of health care dollars that could be focused upon innovation, the Regenerative Medicine model will have not realized its full potential. The Diabetes Transplantation/Regenerative Medicine Model is the first organ to cell transplant model outside of oncology to demonstrate the regenerative medicine paradigm. Since all human tissues can be already recapitulated by human stem cells and key patent holders already exist, outlet or distribution of “more-than-minimally-manipulated stem cell units” as an IND approved under FDA/CBER guidelines can be accomplished via the current HHS/HRSA/Dept of Trans- plant methodology. As cardiovascular stem cell researchers develop human therapeutics utilizing more-than-minimally- manipulated stem cell products, they could be afforded protections from product liability historically enjoyed by the transplant community. Extending the Diabetes Transplant/Regenerative Medicine Model to the more than 5 million Americans with chronic heart failure, cell-based therapies to regenerate myocardial contractility could fill an existing void and be delivered in conjunction with and consistent with existing distribution of organs and tissues via HRSA/Department of Transplantation.
