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1.
J Extracell Vesicles ; 12(2): e12305, 2023 02.
Article in English | MEDLINE | ID: mdl-36775986

ABSTRACT

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.


Subject(s)
Extracellular Vesicles , Nucleic Acids , United States , Extracellular Vesicles/metabolism , Cell Communication , Nucleic Acids/metabolism , Lung/metabolism , Sleep
2.
Clin Transl Sci ; 14(6): 2099-2110, 2021 11.
Article in English | MEDLINE | ID: mdl-34286927

ABSTRACT

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.


Subject(s)
Cell- and Tissue-Based Therapy/economics , Financing, Government , National Heart, Lung, and Blood Institute (U.S.) , Academies and Institutes , Government Regulation , United States
3.
Adv Exp Med Biol ; 1230: 27-42, 2020.
Article in English | MEDLINE | ID: mdl-32285363

ABSTRACT

Organs-on-chips, also known as "tissue chips" or microphysiological systems (MPS), are bioengineered microsystems capable of recreating aspects of human organ physiology and function and are in vitro tools with multiple applications in drug discovery and development. The ability to recapitulate human and animal tissues in physiologically relevant three-dimensional, multi-cellular environments allows applications in the drug development field, including; (1) use in assessing the safety and toxicity testing of potential therapeutics during early-stage preclinical drug development; (2) confirmation of drug/therapeutic efficacy in vitro; and (3) disease modeling of human tissues to recapitulate pathophysiology within specific subpopulations and even individuals, thereby advancing precision medicine efforts. This chapter will discuss the development and evolution of three-dimensional organ models over the past decade, and some of the opportunities offered by MPS technology that are not available through current standard two-dimensional cell cultures, or three-dimensional organoid systems. This chapter will outline future avenues of research in the MPS field, how cutting-edge biotechnology advances are expanding the applications for these systems, and discuss the current and future potential and challenges remaining for the field to address.


Subject(s)
Lab-On-A-Chip Devices , Tissue Array Analysis , Animals , Drug Development , Drug Discovery , Humans
4.
JACC Basic Transl Sci ; 2(3): 335-340, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28736756

ABSTRACT

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 Blood Institute (NHLBI) convened a Working Group of experts on June 2-3, 2016 in Bethesda Maryland to develop recommendations for the NHLBI aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). MSC 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 developing 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 impact 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.

5.
J Thorac Cardiovasc Surg ; 154(1): 165-170, 2017 07.
Article in English | MEDLINE | ID: mdl-28633205

ABSTRACT

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.


Subject(s)
Biomedical Research/standards , Heart Failure/therapy , Heart-Assist Devices , National Heart, Lung, and Blood Institute (U.S.) , Consensus , Heart Failure/diagnosis , Heart Failure/physiopathology , Humans , Prosthesis Design , Recovery of Function , Treatment Outcome , United States , Ventricular Function, Left
6.
ASAIO J ; 63(4): 445-449, 2017.
Article in English | MEDLINE | ID: mdl-28471759

ABSTRACT

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 2-3, 2016, in Bethesda, MD, to develop NHLBI recommendations aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). Mechanical circulatory support 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.


Subject(s)
Heart Failure/therapy , Heart-Assist Devices , Heart/physiopathology , Heart Failure/physiopathology , Humans
7.
J Card Fail ; 23(5): 416-421, 2017 May.
Article in English | MEDLINE | ID: mdl-28433665

ABSTRACT

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 on June 2-3, 2016, in Bethesda, Maryland, to develop recommendations for the NHLBI aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). MSC 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 developing 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 impact 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.


Subject(s)
Assisted Circulation/trends , Heart Failure/therapy , Heart-Assist Devices/trends , National Heart, Lung, and Blood Institute (U.S.)/trends , Recovery of Function/physiology , Congresses as Topic/trends , Heart Failure/diagnosis , Heart Failure/epidemiology , Humans , Maryland/epidemiology , United States/epidemiology
10.
Circ Res ; 112(8): 1097-103, 2013 Apr 12.
Article in English | MEDLINE | ID: mdl-23580772

ABSTRACT

Tissue engineering aims at building 3-dimensional living substitutes that are equal to or better than the damaged tissue to be replaced. The development of such a tissue replacement requires a multidisciplinary approach and careful attention to the optimal cell source, the interactions of growth factors and extracellular milieu, and the scaffolding design. This article is a review of the tissue engineering programs of the National Heart, Lung, and Blood Institute, which support research efforts to translate novel approaches for the treatment of cardiovascular disease. Recent progress is discussed, which highlights some major questions relevant to cardiovascular tissue engineering. The National Heart, Lung, and Blood Institute has a strong interest in tissue engineering and will continue to foster the practical, clinical, and commercial development of research discoveries in this emerging field.


Subject(s)
Cardiovascular Diseases/therapy , National Heart, Lung, and Blood Institute (U.S.)/trends , Research Support as Topic/trends , Tissue Engineering/trends , Animals , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/metabolism , Humans , Research Support as Topic/methods , Tissue Engineering/methods , United States
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