- Email: [email protected]
Technology policy and industry growth: the power of local cluster
S10
Oral Abstracts
promising new method to treat heart failure but results from clinical trials have been mixed. Here, we present results from our study combining BMMC therapy with coronary bypass surgery (CABG). Materials and methods: First, we enrolled 107 ischemic heart failure patients scheduled for CABG. These patients went through a 4- to 12week period with optimized drug therapy. If left ventricular ejection fraction (LVEF) remained 45%, a patient was eligible for the actual study. In a randomized, double-blind manner, the still eligible 39 patients received intramyocardial injections of BMMCs or vehicle intraoperatively into the infarction and border area during CABG. We measured global and segmental LV function and scar size by magnetic resonance imaging (MRI), and viability by positron emission tomography (PET) and singlephoton emission tomography (SPECT), preoperatively and after 1-year follow-up. Results: LVEF, the primary end point measure, improved by a median of 5.6% among controls (IQR 0.2 to 10.1) and by 4.8% in the BMMC patients (IQR -0.5 to 8.2) (P¼0.59). Wall thickening in injected segments rose by a median of 4.5% in the control group (IQR -18.1 to 23.9) and by 5.5% in the BMMC patients (IQR -6.6 to 26.5) (P¼0.68). Viability by PET and SPECT did not differ between the groups. Myocardial scar volume by MRI in injected segments rose by a median of 5.1% in the control group (IQR -3.3 to 10.8) but fell by 13.1% in the BMMC group (IQR -21.4 to -6.5) (P¼0.0002). Conclusions: As an adjunct to CABG, BMMC therapy failed to affect global or local LV systolic function or viability by PET and SPECT during 1-year follow-up. Interestingly, however, it affected one essential prognostic marker: myocardial scar size was significantly reduced by BMMC therapy. Long-term studies are necessary to elucidate this finding’s permanence.
10 EXOSOMES SECRETED BY HUMAN CARDIAC PROGENITORS CONTAIN MICRO-RNA WITH CARDIOPROTECTIVE AND PRO-ANGIOGENIC ACTIVITIES E Cervio1, L Barile1, V Lionetti2, M Matteucci2, M Gherghiceanu3, L Popescu3, T Torre1, F Siclari1, T Moccetti1, G Vassalli1 1 Cardiocentro Ticino, Lugano, Switzerland, 2Istituto Superiore Sant’Anna, Pisa, Italy, 3“Victor Babes” National Institute of Pathology, Bucharest, Romania Background: Secreted factors account, in part, for beneficial effects of transplanted cells into infarcted hearts. Injected cells activate endogenous regenerative processes through paracrine mechanisms including microRNAs (miRNAs). Exosomes (Exo) act as intercellular carriers of proteins and miRNAs. We analyzed the miRNA transcriptional profile of Exo from human cardiac progenitor cells (Exo-CPC) in comparison with Exo from normal human dermal fibroblasts (Exo-F). We studied the effect of hypoxia on miRNAs in Exo-CPC, as well as the cardioprotective effects of selected miRNAs. Methods and Results: CPCs were derived from atrial explants of patients who underwent heart valve surgery. Exo was characterized ultrastructurally by electron microscopy. They were 46.2+/-16.9 nm in size and expressed Exo markers such as CD9, CD63 and CD81. Exo-CPC, but not Exo-F, inhibited cardiomyocyte apoptosis while also stimulating angiogenesis by human endothelial cells in vitro. When injected into rat infarcted hearts, Exo-CPC, but not Exo-F, reduced infarct scar and improved cardiac function in vivo. miRNA transcriptional profiling identified miR-146a-3p, miR181a, miR-132, miR-210-3p, miR- 181b and miR-323-5p among the most highly upregulated miRNAs in Exo-CPC compared to Exo-F. Of these miRNAs, miR-323-5p was further upregulated in Exo isolated from CPCs exposed to hypoxia in vitro. In mouse HL-1 cardiomoycytes subjected to hypoxia and reoxygenation injury, cell viability was significantly increased after transfection with pre-miR-323-5p compared with controls. On the other hand, miR-132 has pro-angiogenic effects. Conclusion: Compared with Exo-F, Exo-CPC is markedly enriched for cardioprotective and pro-angiogenic miRNAs. Hypoxia further increases the miR-323-5p content in Exo isolated from CPCs. In gain-of-function experiments, forced overexpression of this miRNA mediated cardioprotection against hypoxia/reoxygenation injury.
11 PATIENT PARTICIPATION IN REGULATORY DECISIONS REGARDING REGENERATIVE MEDICINE B von Tigerstrom College of Law, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Regulatory agencies responsible for ensuring the safety, efficacy, and quality of medical products for human use are faced with many challenges in appropriately regulating novel medical technologies, including emerging regenerative medicine treatments such as stem cell-based therapies. These agencies have the difficult task of assessing whether the balance of risks and benefits associated with a new treatment justifies approval, in the context of substantial uncertainty. In making these decisions, they are increasingly asked to take into account the perspectives of patients and patient advocacy organizations. These groups may have important information about the risks and benefits of a new treatment and perspectives on how they should be balanced, but their participation in regulatory decision making raises many questions. What type of input should be sought or received from patients and at what stages in the regulatory process? Who should speak for patients and how should the diversity of interests and perspectives among patients be addressed in processes for consultation or input? In what ways should information and views from patients be used in regulatory decisions and how much weight should they be given? Are there special considerations regarding patient participation in the context of novel forms of treatment, such as stem cell-based therapies, or particular types of conditions, such as rare diseases? This paper examines existing and proposed models for patient input into regulatory decision making, seeking to determine how different systems have answered the questions above. It will identify the various approaches used and their advantages and disadvantages, with a view to formulating a set of recommendations or best practices for regulatory agencies and patient organizations to consider.
12 TECHNOLOGY POLICY AND INDUSTRY GROWTH: THE POWER OF LOCAL CLUSTER N Kishi Yokohama National University, Yokohama city, Japan This research focuses on technology policy for the regenerative medicine industry in Germany and Japan, and it suggests the effectiveness of Germany policy, which transfers authorization to the local government. Germany and Japan have common points. Both have restricted dealing with ES cell from ethical viewpoint and have firms with high capability of manufacturing, which provide a strong base for them to build competitive advantages in cell culturing equipment. The focus of technology policy in the regenerative medicine industry is categorized into two types: the first focuses on supporting firms which provide final products such as iPS cell. The second focuses on firms which provide the other production process products, such as cell culturing equipment. Common situation shows that German and Japanese firms should emphasize on supplying the latter products. However, while there are only two product marketed in Japan, Germany has already marketed 29 products. This research explains the cause by the different technology policy. The difference in their technology policy is that the power to implement the policy in Germany is mostly authorized to the local government more than in Japan. Local government has easier accesses to the small and medium size firms in the region and has built a network with the local research institutes. That is why they are superior to finding the appropriate support for the local firms needs and for making a tie between firms and research institutions. The result is that there are some local clusters with definite characteristics in Germany. On the other hand, in Japan, the most authorization to implement them is still in the central government. In the dawn of the industry, interdisciplinary knowledge is needed to overcome high uncertainty. In Germany, diversity of the authorized local clusters realizes that.
13 A HIGHLY EFFICIENT CULTURE METHOD FOR GROWTH AND DETECTION OF UNDIFFERENTIATED HUMAN
Oral Abstracts
promising new method to treat heart failure but results from clinical trials have been mixed. Here, we present results from our study combining BMMC therapy with coronary bypass surgery (CABG). Materials and methods: First, we enrolled 107 ischemic heart failure patients scheduled for CABG. These patients went through a 4- to 12week period with optimized drug therapy. If left ventricular ejection fraction (LVEF) remained 45%, a patient was eligible for the actual study. In a randomized, double-blind manner, the still eligible 39 patients received intramyocardial injections of BMMCs or vehicle intraoperatively into the infarction and border area during CABG. We measured global and segmental LV function and scar size by magnetic resonance imaging (MRI), and viability by positron emission tomography (PET) and singlephoton emission tomography (SPECT), preoperatively and after 1-year follow-up. Results: LVEF, the primary end point measure, improved by a median of 5.6% among controls (IQR 0.2 to 10.1) and by 4.8% in the BMMC patients (IQR -0.5 to 8.2) (P¼0.59). Wall thickening in injected segments rose by a median of 4.5% in the control group (IQR -18.1 to 23.9) and by 5.5% in the BMMC patients (IQR -6.6 to 26.5) (P¼0.68). Viability by PET and SPECT did not differ between the groups. Myocardial scar volume by MRI in injected segments rose by a median of 5.1% in the control group (IQR -3.3 to 10.8) but fell by 13.1% in the BMMC group (IQR -21.4 to -6.5) (P¼0.0002). Conclusions: As an adjunct to CABG, BMMC therapy failed to affect global or local LV systolic function or viability by PET and SPECT during 1-year follow-up. Interestingly, however, it affected one essential prognostic marker: myocardial scar size was significantly reduced by BMMC therapy. Long-term studies are necessary to elucidate this finding’s permanence.
10 EXOSOMES SECRETED BY HUMAN CARDIAC PROGENITORS CONTAIN MICRO-RNA WITH CARDIOPROTECTIVE AND PRO-ANGIOGENIC ACTIVITIES E Cervio1, L Barile1, V Lionetti2, M Matteucci2, M Gherghiceanu3, L Popescu3, T Torre1, F Siclari1, T Moccetti1, G Vassalli1 1 Cardiocentro Ticino, Lugano, Switzerland, 2Istituto Superiore Sant’Anna, Pisa, Italy, 3“Victor Babes” National Institute of Pathology, Bucharest, Romania Background: Secreted factors account, in part, for beneficial effects of transplanted cells into infarcted hearts. Injected cells activate endogenous regenerative processes through paracrine mechanisms including microRNAs (miRNAs). Exosomes (Exo) act as intercellular carriers of proteins and miRNAs. We analyzed the miRNA transcriptional profile of Exo from human cardiac progenitor cells (Exo-CPC) in comparison with Exo from normal human dermal fibroblasts (Exo-F). We studied the effect of hypoxia on miRNAs in Exo-CPC, as well as the cardioprotective effects of selected miRNAs. Methods and Results: CPCs were derived from atrial explants of patients who underwent heart valve surgery. Exo was characterized ultrastructurally by electron microscopy. They were 46.2+/-16.9 nm in size and expressed Exo markers such as CD9, CD63 and CD81. Exo-CPC, but not Exo-F, inhibited cardiomyocyte apoptosis while also stimulating angiogenesis by human endothelial cells in vitro. When injected into rat infarcted hearts, Exo-CPC, but not Exo-F, reduced infarct scar and improved cardiac function in vivo. miRNA transcriptional profiling identified miR-146a-3p, miR181a, miR-132, miR-210-3p, miR- 181b and miR-323-5p among the most highly upregulated miRNAs in Exo-CPC compared to Exo-F. Of these miRNAs, miR-323-5p was further upregulated in Exo isolated from CPCs exposed to hypoxia in vitro. In mouse HL-1 cardiomoycytes subjected to hypoxia and reoxygenation injury, cell viability was significantly increased after transfection with pre-miR-323-5p compared with controls. On the other hand, miR-132 has pro-angiogenic effects. Conclusion: Compared with Exo-F, Exo-CPC is markedly enriched for cardioprotective and pro-angiogenic miRNAs. Hypoxia further increases the miR-323-5p content in Exo isolated from CPCs. In gain-of-function experiments, forced overexpression of this miRNA mediated cardioprotection against hypoxia/reoxygenation injury.
11 PATIENT PARTICIPATION IN REGULATORY DECISIONS REGARDING REGENERATIVE MEDICINE B von Tigerstrom College of Law, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Regulatory agencies responsible for ensuring the safety, efficacy, and quality of medical products for human use are faced with many challenges in appropriately regulating novel medical technologies, including emerging regenerative medicine treatments such as stem cell-based therapies. These agencies have the difficult task of assessing whether the balance of risks and benefits associated with a new treatment justifies approval, in the context of substantial uncertainty. In making these decisions, they are increasingly asked to take into account the perspectives of patients and patient advocacy organizations. These groups may have important information about the risks and benefits of a new treatment and perspectives on how they should be balanced, but their participation in regulatory decision making raises many questions. What type of input should be sought or received from patients and at what stages in the regulatory process? Who should speak for patients and how should the diversity of interests and perspectives among patients be addressed in processes for consultation or input? In what ways should information and views from patients be used in regulatory decisions and how much weight should they be given? Are there special considerations regarding patient participation in the context of novel forms of treatment, such as stem cell-based therapies, or particular types of conditions, such as rare diseases? This paper examines existing and proposed models for patient input into regulatory decision making, seeking to determine how different systems have answered the questions above. It will identify the various approaches used and their advantages and disadvantages, with a view to formulating a set of recommendations or best practices for regulatory agencies and patient organizations to consider.
12 TECHNOLOGY POLICY AND INDUSTRY GROWTH: THE POWER OF LOCAL CLUSTER N Kishi Yokohama National University, Yokohama city, Japan This research focuses on technology policy for the regenerative medicine industry in Germany and Japan, and it suggests the effectiveness of Germany policy, which transfers authorization to the local government. Germany and Japan have common points. Both have restricted dealing with ES cell from ethical viewpoint and have firms with high capability of manufacturing, which provide a strong base for them to build competitive advantages in cell culturing equipment. The focus of technology policy in the regenerative medicine industry is categorized into two types: the first focuses on supporting firms which provide final products such as iPS cell. The second focuses on firms which provide the other production process products, such as cell culturing equipment. Common situation shows that German and Japanese firms should emphasize on supplying the latter products. However, while there are only two product marketed in Japan, Germany has already marketed 29 products. This research explains the cause by the different technology policy. The difference in their technology policy is that the power to implement the policy in Germany is mostly authorized to the local government more than in Japan. Local government has easier accesses to the small and medium size firms in the region and has built a network with the local research institutes. That is why they are superior to finding the appropriate support for the local firms needs and for making a tie between firms and research institutions. The result is that there are some local clusters with definite characteristics in Germany. On the other hand, in Japan, the most authorization to implement them is still in the central government. In the dawn of the industry, interdisciplinary knowledge is needed to overcome high uncertainty. In Germany, diversity of the authorized local clusters realizes that.
13 A HIGHLY EFFICIENT CULTURE METHOD FOR GROWTH AND DETECTION OF UNDIFFERENTIATED HUMAN