S10 Oral Abstracts

promising new method to treat heart failure but results from clinical trials havebeen mixed. Here, we present results from our study combining BMMCtherapy with coronary bypass surgery (CABG).

Materials and methods: First, we enrolled 107 ischemic heart failurepatients scheduled for CABG. These patients went through a 4- to 12-week period with optimized drug therapy. If left ventricular ejectionfraction (LVEF) remained �45%, a patient was eligible for the actualstudy. In a randomized, double-blind manner, the still eligible 39 patientsreceived intramyocardial injections of BMMCs or vehicle intraoperativelyinto the infarction and border area during CABG. We measured global andsegmental LV function and scar size by magnetic resonance imaging(MRI), and viability by positron emission tomography (PET) and single-photon emission tomography (SPECT), preoperatively and after 1-yearfollow-up.

Results: LVEF, the primary end point measure, improved by a median of5.6% 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 amedian of 4.5% in the control group (IQR -18.1 to 23.9) and by 5.5% inthe BMMC patients (IQR -6.6 to 26.5) (P¼0.68). Viability by PET andSPECT did not differ between the groups. Myocardial scar volume by MRIin 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 affectglobal or local LV systolic function or viability by PET and SPECTduring 1-year follow-up. Interestingly, however, it affected one essentialprognostic marker: myocardial scar size was significantly reduced byBMMC therapy. Long-term studies are necessary to elucidate this find-ing’s permanence.

10EXOSOMES SECRETED BY HUMAN CARDIAC PROGENITORSCONTAIN MICRO-RNA WITH CARDIOPROTECTIVE ANDPRO-ANGIOGENIC ACTIVITIESE Cervio1, L Barile1, V Lionetti2, M Matteucci2, M Gherghiceanu3,L Popescu3, T Torre1, F Siclari1, T Moccetti1, G Vassalli11Cardiocentro 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 oftransplanted cells into infarcted hearts. Injected cells activate endogenousregenerative processes through paracrine mechanisms including microRNAs(miRNAs). Exosomes (Exo) act as intercellular carriers of proteins andmiRNAs. We analyzed the miRNA transcriptional profile of Exo from hu-man cardiac progenitor cells (Exo-CPC) in comparison with Exo fromnormal human dermal fibroblasts (Exo-F). We studied the effect of hypoxiaon miRNAs in Exo-CPC, as well as the cardioprotective effects of selectedmiRNAs.

Methods and Results: CPCs were derived from atrial explants of patientswho underwent heart valve surgery. Exo was characterized ultrastructurallyby electron microscopy. They were 46.2+/-16.9 nm in size and expressedExo markers such as CD9, CD63 and CD81. Exo-CPC, but not Exo-F,inhibited cardiomyocyte apoptosis while also stimulating angiogenesis byhuman endothelial cells in vitro. When injected into rat infarcted hearts,Exo-CPC, but not Exo-F, reduced infarct scar and improved cardiac func-tion in vivo. miRNA transcriptional profiling identified miR-146a-3p, miR-181a, miR-132, miR-210-3p, miR- 181b and miR-323-5p among the mosthighly upregulated miRNAs in Exo-CPC compared to Exo-F. Of thesemiRNAs, miR-323-5p was further upregulated in Exo isolated from CPCsexposed to hypoxia in vitro. In mouse HL-1 cardiomoycytes subjected tohypoxia and reoxygenation injury, cell viability was significantly increasedafter transfection with pre-miR-323-5p compared with controls. On theother hand, miR-132 has pro-angiogenic effects.

Conclusion: Compared with Exo-F, Exo-CPC is markedly enriched forcardioprotective and pro-angiogenic miRNAs. Hypoxia further increases themiR-323-5p content in Exo isolated from CPCs. In gain-of-function experi-ments, forced overexpression of this miRNA mediated cardioprotection againsthypoxia/reoxygenation injury.

11PATIENT PARTICIPATION IN REGULATORY DECISIONSREGARDING REGENERATIVE MEDICINEB von TigerstromCollege of Law, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

Regulatory agencies responsible for ensuring the safety, efficacy, andquality of medical products for human use are faced with many challengesin appropriately regulating novel medical technologies, including emergingregenerative medicine treatments such as stem cell-based therapies. Theseagencies have the difficult task of assessing whether the balance of risksand benefits associated with a new treatment justifies approval, in thecontext of substantial uncertainty. In making these decisions, they areincreasingly asked to take into account the perspectives of patients andpatient advocacy organizations. These groups may have important infor-mation about the risks and benefits of a new treatment and perspectives onhow they should be balanced, but their participation in regulatory decisionmaking raises many questions. What type of input should be sought orreceived from patients and at what stages in the regulatory process? Whoshould speak for patients and how should the diversity of interests andperspectives among patients be addressed in processes for consultation orinput? In what ways should information and views from patients be usedin regulatory decisions and how much weight should they be given? Arethere special considerations regarding patient participation in the contextof novel forms of treatment, such as stem cell-based therapies, or partic-ular types of conditions, such as rare diseases? This paper examinesexisting and proposed models for patient input into regulatory decisionmaking, seeking to determine how different systems have answered thequestions above. It will identify the various approaches used and theiradvantages and disadvantages, with a view to formulating a set of recom-mendations or best practices for regulatory agencies and patient organi-zations to consider.

12TECHNOLOGY POLICY AND INDUSTRY GROWTH: THEPOWER OF LOCAL CLUSTERN KishiYokohama National University, Yokohama city, Japan

This research focuses on technology policy for the regenerative medicine in-dustry in Germany and Japan, and it suggests the effectiveness of Germanypolicy, which transfers authorization to the local government. Germany andJapan have common points. Both have restricted dealing with ES cell fromethical viewpoint and have firms with high capability of manufacturing, whichprovide a strong base for them to build competitive advantages in cellculturing equipment. The focus of technology policy in the regenerativemedicine industry is categorized into two types: the first focuses on sup-porting firms which provide final products such as iPS cell. The second fo-cuses on firms which provide the other production process products, such ascell culturing equipment. Common situation shows that German and Japa-nese firms should emphasize on supplying the latter products. However, whilethere are only two product marketed in Japan, Germany has already marketed29 products. This research explains the cause by the different technologypolicy. The difference in their technology policy is that the power toimplement the policy in Germany is mostly authorized to the local govern-ment more than in Japan. Local government has easier accesses to the smalland medium size firms in the region and has built a network with the localresearch institutes. That is why they are superior to finding the appropriatesupport for the local firms needs and for making a tie between firms andresearch institutions. The result is that there are some local clusters withdefinite characteristics in Germany. On the other hand, in Japan, the mostauthorization to implement them is still in the central government. In thedawn of the industry, interdisciplinary knowledge is needed to overcome highuncertainty. In Germany, diversity of the authorized local clusters realizesthat.

13A HIGHLY EFFICIENT CULTURE METHOD FOR GROWTHAND DETECTION OF UNDIFFERENTIATED HUMAN