The NHLBI SMARTT Program: A Novel Approach to Facilitate Translational Research for Heart, Lung and Blood Diseases.

The National Heart, Lung, and Blood Institute (NHLBI), one of the 27 Institutes/Centers within the National Institutes of Health (NIH), has a strong interest in promoting translational research. This interest can be traced to its mission statement, which reads in part: “The NHLBI stimulates basic discoveries about the causes of disease, enables the translation of basic discoveries into clinical practice, fosters training and mentoring of emerging scientists and physicians, and communicates research advances to the public.” (www.

2015 proceedings of the National Heart, Lung, and Blood Institute's State of the Science in Transfusion Medicine symposium.

On March 25 and 26, 2015, the National Heart, Lung, and Blood Institute sponsored a meeting on the State of the Science in Transfusion Medicine on the National Institutes of Health (NIH) campus in Bethesda, Maryland, which was attended by a diverse group of 330 registrants. The meeting's goal was to identify important research questions that could be answered in the next 5 to 10 years and which would have the potential to transform the clinical practice of transfusion medicine. These questions could be addressed by basic, translational, and/or clinical research studies and were focused on four areas: the three "classical" transfusion products (i.

One size will never fit all: the future of research in pediatric transfusion medicine.

There is concern at the National Heart, Lung, and Blood Institute (NHLBI) and among transfusion medicine specialists regarding the small number of investigators and studies in the field of pediatric transfusion medicine (PTM). Accordingly, the objective of this article is to provide a snapshot of the clinical and translational PTM research considered to be of high priority by pediatricians, neonatologists, and transfusion medicine specialists. Included is a targeted review of three research areas of importance: (i) transfusion strategies, (ii) short- and long-term clinical consequences, and (iii) transfusion-transmitted infectious diseases.

Strategies for more rapid translation of cellular therapies for children: a US perspective.

Clinical trials for pediatric diseases face many challenges, including trial design, accrual, ethical considerations for children as research subjects, and the cost of long-term follow-up studies. In September 2011, the Production Assistance for Cellular Therapies Program, funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health, sponsored a workshop, "Cell Therapy for Pediatric Diseases: A Growing Frontier," with the overarching goal of optimizing the path of discovery in research involving novel cellular therapeutic interventions for debilitating pediatric conditions with few or no available treatment options. Academic and industry investigators in the fields of cellular therapy and regenerative medicine described the obstacles encountered in conducting a clinical trial from concept to conclusion.

The role of comparative effectiveness research in transfusion medicine clinical trials: proceedings of a National Heart, Lung, and Blood Institute workshop.

Comparative effectiveness research (CER) is the study of existing treatments or ways to deliver health care to determine what intervention works best under specific circumstances. CER evaluates evidence from existing studies or generates new evidence, in different populations and under specific conditions in which the treatments are actually used. CER does not embrace one research design over another but compares treatments and variations in practice using methods that are most likely to yield widely generalizable results that are directly relevant to clinical practice.

Production Assistance for Cellular Therapies (PACT): four-year experience from the United States National Heart, Lung, and Blood Institute (NHLBI) contract research program in cell and tissue therapies.

Background: In 2002, the US National Heart, Lung, and Blood Institute (NHLBI) conducted a workshop to determine needs of the cell therapy community. A consensus emerged that improved access to cGMP facilities, regulatory assistance, and training would foster the advancement of cellular therapy.

Study Design And Methods: A 2003 NHLBI request for proposals resulted in four contracts being awarded to three cell-manufacturing facilities (Baylor College of Medicine, University of Minnesota, and University of Pittsburgh) and one administrative center (The EMMES Corporation).

Pediatric transfusion medicine: development of a critical mass.

Many significant events have occurred in the recent past that beg a broad audience to address the question "What is pediatric transfusion medicine?" Herein, we list some of these events and their relevance below and attempt to provide an answer for this question. Indeed, several issues regarding the subspecialty of pediatric transfusion medicine (PTM) are particularly timely, and it appears that a critical mass, or a nidus capable of becoming a critical mass, is developing in PTM.

Cold temperatures reduce the sensitivity of stored platelets to disaggregating agents.

In this study, we compared the effect of signal transduction inhibitors on fibrinogen binding, aggregation, the activation state of GPIIb-IIIa, and cytosolic calcium levels in cold and room temperature-stored platelets. Cold-stored platelets have a higher sensitivity to agonist-induced aggregation when compared to room temperature-stored platelets. We also found that cold-stored platelets had a significantly higher aggregation response to ADP and epinephrine, while platelets stored at room temperature responded poorly to these agonists (mean values of 61 vs.

Adenoviral vectors do not induce, inhibit, or potentiate human platelet aggregation.

Adenoviruses are commonly used as vectors in human clinical gene therapy trials. High doses of intravenous adenovirus vectors have been associated with development of thrombocytopenia of undetermined origin. Viral internalization requires the presence cell surface integrins, alpha(v)beta(3) or alpha(v)beta(5), that can blind ligands with a arginine-glycine-aspartic acid (RGD) sequence.

Toxicity of a first-generation adenoviral vector in rhesus macaques.

We constructed a first-generation adenovirus vector (AVC3FIX5) that we used to assess the rhesus macaque as a nonhuman primate model for preclinical testing of hemophilia B gene therapy vectors. Although we succeeded in our primary objective of demonstrating expression of human factor IX we encountered numerous toxic side effects that proved to be dose limiting. Following intravenous administration of AVC3FIX5 at doses of 3.