Current challenges and future directions for engineering extracellular vesicles for heart, lung, blood and sleep diseases.

Extracellular vesicles (EVs) carry diverse bioactive components including nucleic acids, proteins, lipids and metabolites that play versatile roles in intercellular and interorgan communication. The capability to modulate their stability, tissue-specific targeting and cargo render EVs as promising nanotherapeutics for treating heart, lung, blood and sleep (HLBS) diseases. However, current limitations in large-scale manufacturing of therapeutic-grade EVs, and knowledge gaps in EV biogenesis and heterogeneity pose significant challenges in their clinical application as diagnostics or therapeutics for HLBS diseases. To address these challenges, a strategic workshop with multidisciplinary experts in EV biology and U.S. Food and Drug Administration (USFDA) officials was convened by the National Heart, Lung and Blood Institute. The presentations and discussions were focused on summarizing the current state of science and technology for engineering therapeutic EVs for HLBS diseases, identifying critical knowledge gaps and regulatory challenges and suggesting potential solutions to promulgate translation of therapeutic EVs to the clinic. Benchmarks to meet the critical quality attributes set by the USFDA for other cell-based therapeutics were discussed. Development of novel strategies and approaches for scaling-up EV production and the quality control/quality analysis (QC/QA) of EV-based therapeutics were recognized as the necessary milestones for future investigations.Funding information: National Heart, Lung, and Blood Institute, Grant/Award Numbers: HL 122596, HL124021, HL124074, HL128297, HL141080, HL155346-01, R35HL150807, R56HL141206 Prithu Sundd was supported by NIH-NHLBI R01 grants (HL128297 and HL141080) and 18TPA34170588 from American Heart Association. Stephen Y. Chan was supported by NIH grants R01 HL124021 and HL 122596 as well as AHA grant 18EIA33900027. SuamyaDaswas supported by NIH grants R35HL150807, UH3 TR002878 andAHASFRN35120123. ZhenjiaWangwas supported by NIH grant (R01EB027078). Pilar Martín was supported by MCIN-ISCIII-Fondo de Investigación Sanitaria grant PI22/01759. KennethW.Witwer was supported in part by NIH grants R01AI144997, R01DA047807, R33MH118164 andUH3CA241694. Tianji Chen was supported by AHA Career Development Award 18CDA34110301, Gilead Sciences Research Scholars Program in PAH, NIH-NHLBI grant R56HL141206 and Chicago Biomedical ConsortiumCatalyst Award. EduardoMarbán was supported byNIH R01 HL124074 and HL155346-01.S

The coral core microbiome identifies rare bacterial taxa as ubiquitous endosymbionts

© 2015 International Society for Microbial Ecology All rights reserved. Despite being one of the simplest metazoans, corals harbor some of the most highly diverse and abundant microbial communities. Differentiating core, symbiotic bacteria from this diverse hostassociated consortium is essential for characterizing the functional contributions of bacteria but has not been possible yet. Here we characterize the coral core microbiome and demonstrate clear phylogenetic and functional divisions between the micro-scale, niche habitats within the coral host. In doing so, we discover seven distinct bacterial phylotypes that are universal to the core microbiome of coral species, separated by thousands of kilometres of oceans. The two most abundant phylotypes are co-localized specifically with the corals' endosymbiotic algae and symbiont-containing host cells. These bacterial symbioses likely facilitate the success of the dinoflagellate endosymbiosis with corals in diverse environmental regimes

Advancing the Science of Myocardial Recovery With Mechanical Circulatory Support

Summary: The medical burden of heart failure (HF) has spurred interest in clinicians and scientists to develop therapies to restore the function of a failing heart. To advance this agenda, the National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group of experts from June 2 to 3, 2016, in Bethesda, Maryland, to develop NHLBI recommendations aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). MCS devices effectively reduce volume and pressure overload that drives the cycle of progressive myocardial dysfunction, thereby triggering structural and functional reverse remodeling. Research in this field could be innovative in many ways, and the Working Group specifically discussed opportunities associated with genome-phenome systems biology approaches; genetic epidemiology; bioinformatics and precision medicine at the population level; advanced imaging modalities, including molecular and metabolic imaging; and the development of minimally invasive surgical and percutaneous bioengineering approaches. These new avenues of investigations could lead to new treatments that target phylogenetically conserved pathways involved in cardiac reparative mechanisms. A central point that emerged from the NHLBI Working Group meeting was that the lessons learned from the MCS investigational setting can be extrapolated to the broader HF population. With the precedents set by the significant effect of studies of other well-controlled and tractable subsets on larger populations, such as the genetic work in both cancer and cardiovascular disease, the work to improve our understanding of cardiac recovery and resilience in MCS patients could be transformational for the greater HF population. Key Words: cardiac remodeling, mechanical circulatory support, myocardial recovery, ventricular assist device

Report of the National Heart, Lung, and Blood Institute Working Group on Sex Differences Research in Cardiovascular Disease: Scientific Questions and Challenges.

Hypertension 2016 May; 67(5):802-7

The National Heart, Lung, and Blood Institute‐funded Production Assistance for Cellular Therapies (PACT) program: Eighteen years of cell therapy

The Production Assistance for Cellular Therapies (PACT) Program, is funded and supported by the US Department of Health and Human Services’ National Institutes of Health (NIH) National Heart Lung and Blood Institute (NHLBI) to advance development of somatic cell and genetically modified cell therapeutics in the areas of heart, lung, and blood diseases. The program began in 2003, continued under two competitive renewals, and ended June 2021. PACT has supported cell therapy product manufacturing, investigational new drug enabling preclinical studies, and translational services, and has provided regulatory assistance for candidate cell therapy products that may aid in the repair and regeneration of damaged/diseased cells, tissues, and organs. PACT currently supports the development of novel cell therapies through five cell processing facilities. These facilities offer manufacturing processes, analytical development, technology transfer, process scale‐up, and preclinical development expertise necessary to produce cell therapy products that are compliant with Good Laboratory Practices, current Good Manufacturing Practices, and current Good Tissue Practices regulations. The Emmes Company, LLC, serves as the Coordinating Center and assists with the management and coordination of PACT and its application submission and review process. This paper discusses the impact and accomplishments of the PACT program on the cell therapy field and its evolution over the duration of the program. It highlights the work that has been accomplished and provides a foundation to build future programs with similar goals to advance cellular therapeutics in a coordinated and centralized programmatic manner to support unmet medical needs within NHLBI purview

More Power to the Pill: The Impact of Contraceptive Freedom on Women's Life Cycle Labor Supply

The release of Enovid in 1960, the first birth control pill, afforded U. S. women unprecedented freedom to plan childbearing and their careers. This paper uses plausibly exogenous variation in state consent laws to evaluate the causal impact of the pill on the timing of first births and extent and intensity of women's labor-force participation. The results suggest that legal access to the pill before age 21 significantly reduced the likelihood of a first birth before age 22, increased the number of women in the paid labor force, and raised the number of annual hours worked. Copyright (c) President and Fellows of Harvard College and the Massachusetts Institute of Technology..