Showing 21 ideas for tag "heart"

Goal 3: Advance Translational Research

Research Opportunities in HLB to Facilitate Aging in Place

There is a need for greater evidence-based research over the next 5-10 years to reduce healthcare costs, reduce hospitalizations, and support older persons with significant heart, lung, blood, sleep conditions to remain in their private homes if feasible, if technology is utilized that fosters clinical and epidemiologic research.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

No other force will have as big of an impact on our health system as the unalterable rate of our aging population and subsequent increased rate of heart, lung and blood diseases. The impact of doing nothing is unforeseeable.

Feasibility and challenges of addressing this CQ or CC

Evidence-based research over the next 5-10 years to reduce healthcare costs, reduce hospitalizations, and support older persons with significant heart, lung and blood conditions remain in their private homes is feasible if technology is utilized that fosters clinical and epidemiologic research.
Many cardiovascular risk factors increase as the population ages including uncontrolled systolic hypertension and atherosclerosis both contributing to the well-being of our society and increasingly high health care costs (Izzo, Levy, & Black, 2012). No other force will have as big of an impact on our health system as the unalterable rate of our aging population and subsequent increased rate of heart, lung and blood diseases. The impact of doing nothing is unforeseeable.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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35 up votes
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Goal 3: Advance Translational Research

What is the optimal way to improve cardiac arrest resuscitation?

Sudden Death from cardiac arrest and gaps in knowledge of emergency cardiovascular care are the #1 killer of more than 400,000 Americans each year. This epidemic of death and disability is largely ignored and underfunded by NIH and all funding agencies and kills more than HIV, Cancer, Diabetes, and infectious diseases. There is no national registry of cardiac arrest, no mandatory reporting, and poor funding for both fundamental,... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Answering this question will save more lives and quality of life-years than all other infectious diseases in North America. The potential interventions are well developed and we need more fundamental, translational and implementation science to impact this most significant problem. An upcoming IOM report on needless deaths resulting from cardiac arrest is anticipated to be published in 2015.

Feasibility and challenges of addressing this CQ or CC

Very feasible, just needs support and funding. A call to arms is being issued by the American Heart Association and Institute of Medicine. The roadmap is outlined, and all we need to do is follow the roadmap.

Name of idea submitter and other team members who worked on this idea Vinay Nadkarni MD

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19 net votes
37 up votes
18 down votes
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Goal 3: Advance Translational Research

New Targets for the Treatment of Heart Failure

Heart failure (HF) is one of the major health challenges in the 21st Century. Its prevalence is due a growing number of patients who survive heart attacks, who later develop heart failure; and the high incidence of diabetes leading to diabetic cardiomyopathy. Current treatments for HF only slow the progression of the disease; no treatment stops or reverses this adverse sequence. These limitations provoke the question... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

The current treatment regimens for patients with heart failure (HF) focus on strategies to reduce cardiac work (by reducing heart rate, beta-blockers), afterload reduction (ACE inhibitors), and decrease in preload/blood volume (ACE inhibitors, aldosterone antagonists, diuretics). None of these treatments stop or reverse the progression of the disease. A recent gene therapy trial designed to improve cardiac contractility and calcium handling in HF has failed in clinical trials. Perhaps the reason that the current and experimental treatments have not produced an outcome of stopping or reversing the progression of the disease relates to the "cell" they are targeting. In this regard, the current treatments principally target cardiac myocytes, but there is evidence that vascular perfusion abnormalities may also be involved in the disease. One such piece of evidence relates to the diffuse fibrosis occurring in the failing hearts. Such fibrosis is often referred to as replacement fibrosis in that the fibrotic tissue has replaced cardiac myocytes which died. This death could be the result of a perfusion abnormalities caused by inadequate dilation of the coronary resistance vessels. Thus, is heart failure a pathology involving both the coronary circulation and cardiac muscle? In this regard, future investigations of heart failure consider cardiac-coronary interactions leading to perfusion abnormalities as a key factor in the progression of heart failure.

Feasibility and challenges of addressing this CQ or CC

The challenge of addressing a coronary vascular contribution to heart failure would involve an interdisciplinary approach using genetic models with cardiac and/or vascular (smooth muscle and endothelium) expression or knock-out of key genes involved in cardiac function and vascular control. Sophisticated measurements of cardiac function and metabolic status of the heart using echocardiography, MRI, PET and a L-Band EPR would provide insight into flow-function-metabolism-oxygenation relations in the normal and failing heart.

Name of idea submitter and other team members who worked on this idea William M Chilian

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18 up votes
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Goal 3: Advance Translational Research

Safety and effectiveness of new direct oral anticoagulants

What is the optimal use of new direct oral anticoagulants?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Vitamin K antagonist, warfarin, has traditionally been the mainstay of anticoagulation therapy. It requires frequent monitoring to maintain safe and effective dose and is associated with many food and drug interactions. A new generation of direct oral anticoagulants has been developed to overcome such shortcomings.
Two main classes of new direct oral anticoagulants are available: factor Xa inhibitors and factor IIa (thrombin) inhibitors. Their mechanism of action involves direct inhibition of a single factor within the coagulation cascade to exert an anticoagulant effect. The industry is positioning them as monitoring-free universal warfarin replacement products. However, use of new direct oral anticoagulants introduces two major clinical issues: majority of new generation anticoagulants do not have developed dose-monitoring assay and do not have antidotes to rapidly restore blood coagulation properties in patients with trauma, emergent surgery, or anticoagulation overdose. Addressing these issues would positively impact cardiovascular, pulmonary, benign hematology, and orthopedic services worldwide.
While the idea of a universal, low-maintenance, “one dose fits all” anticoagulant is highly appealing to both patients and physicians, it may be feasible to consider more targeted approach, where each new anticoagulant would be assessed for most plausible effect in the specific patient population with consideration to genetic s, sex, race, age, thrombosis history, and obesity

Feasibility and challenges of addressing this CQ or CC

Rapid advancement in the field of new generation direct oral anticoagulants and multiplicity of new drugs introduce opportunity to conduct comparative effectiveness research and assess how different characteristics of new products may be appropriate for different patients. Increased use of new direct oral anticoagulants requires expedited development of assays and antidotes for safe and efficient therapy of millions of Americans.

 

A challenge is that the majority of the clinical trials for new direct oral anticoagulants were conducted by the industry with the main goal of demonstrating superiority, or non-inferiority to warfarin. Secondary analyses of these trials’ data for efficacy in specific patient population may be difficult. Prospective clinical studies in this area may require large sample size and establishing collaboration between hematologists and other involved clinicians.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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31 up votes
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Goal 3: Advance Translational Research

Heart Valve Engineering from Basic Science to Translation

Heart valve disease is third cardiac condition in the U.S.affecting 2.5% of adult population. There are multiple questions with regard to heart valve engineering from basic science to translation. Many unknowns exist related to calcification and its potential mechanisms in transcatheter heart valve (THV), for example, due to stent crimping that can critically affect the valve durability. This is particularly important... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Developing self-regenerating heart valves; Does stent-crimping damage prone the valve's leaflet to premature calcification in transcatheter heart valves? what are the basic biological elements and pathways that result in valve calcification? how can we translate the basic science related to heart valve biology into clinically viable technologies that improve patients condition?

Name of idea submitter and other team members who worked on this idea Arash Kheradvar

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Goal 3: Advance Translational Research

Regenerative Medicine 2.0 in Heart and Lung Research - Back to the Drawing Board

Stem cell therapies have been quite successful in hematologic disease but the outcomes of clinical studies using stem cells for cardiopulmonary disease have been rather modest.

Explanations for this discrepancy such as the fact that our blood has a high rate of physiologic, endogenous turnover and regeneration whereas these processes occur at far lower rates in the heart and lung. Furthermore, hematopoietic stem cells... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Some barriers to successfully implementing cardiopulmonary regeneration include the complex heterogeneous nature of the heart and lung.

Hematopoietic stem cells can give rise to all hematopoietic cells but the heart and lung appear to contain numerous pools of distinct regenerative stem and progenitor cells, many of which only regenerate a limited cell type in the respective organ. The approach of injecting one stem cell type that worked so well for hematopoietic stem cells is unlikely to work in the heart and lung.

We therefore need new approaches which combine multiple regenerative cell types and pathways in order to successfully repair and regenerate heart and lung tissues. These cell types will likely also require specific matrix cues since there are numerous, heterogeneous microenvironments in the heart and lung.

If we rethink our current approaches to regenerating the heart and lung and we use combined approaches in which multiple cell types and microevironments are concomitantly regenerated (ideally by large scale collaborations between laboratories), we are much more likely to achieve success.

This will represent a departure from the often practiced "Hey, let us inject our favorite cell" approach that worked so well in hematologic disease but these novel, combined approaches targeting multiple endogenous and/or exogenous regenerative cells could fundamentally change our ability to treat heart and lung disease.

Name of idea submitter and other team members who worked on this idea Jalees Rehman

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7 net votes
11 up votes
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Goal 3: Advance Translational Research

Human Heart Systems Biology

In the human failing heart, it is the systems biology that ultimately fails: electrical, mechanical, and chemical perturbations in their function do not manifest in isolation, but critically impact on each other in health and disease. Investigation of human myocardium, unlike inbred rodent models, is challenging since no two humans are identical. There is a need for the collection and assessment of clinical patient data,... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Procured/stored tissue from these hearts could be made available NHLBI/NIH-wide, and studied by a large number of investigators on protein levels, RNA/DNA level, and/or histological assessments. This data could then be correlated to any other parameter assessed on these hearts, providing correlative guidance, through systems biology/neural network programming, for future mechanistic studies. For each additional parameter investigated, the number of correlation analysis (with any and all parameters, including clinical and biometric parameters) would mathematically double.

Feasibility and challenges of addressing this CQ or CC

Supporting the basic collection of these in vivo and in vitro parameters and possibly the logistics for tissue distribution to collect correlative mechanical, proteomics, genomics, and histology data for correlation with the in vivo and in vitro data would allow for an NIH/NHLBI-wide translational approach to human heart failure that could encompass everyone’s “favorite” molecule, protein, pathway, and disease etiology. A logistical challenge is that such a project would likely exceed the funding of a single standard grant, but more importantly would surely exceed the standard 4-5 year duration, requiring long-term vision, planning, and buy in from NIH/NHBLI and investigators.

Name of idea submitter and other team members who worked on this idea Paul Janssen

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6 net votes
13 up votes
7 down votes
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Goal 3: Advance Translational Research

Leveraging big data for T4 translation research

What approaches can help leverage the emerging big data in health and health care for observational and interventional implementation research in heart, lung, blood, sleep diseases?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

• Integration of big data analytics into T4 research study design and interventions development
• Innovative linkages across multiple health and non-health sector data
• Innovative methods to analyze big data linked across sectors
• Various communities are using big data analytics to understand population health data (e.g. electronic medical records s) and opportunities exist for consolidation of these efforts and standardization of methodologies

Feasibility and challenges of addressing this CQ or CC

• NIH now has focus on big data in its formative stages
• Significant amount of NIH’s budget is/will be dedicated to big data research
• NHLBI can leverage NIH’s investment by foster research in D&I big data analytics and systems science
• Future investment in big data should yield opportunities and focus efforts

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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Goal 3: Advance Translational Research

Advancing Translational Research

Ensuring that basic science is translated into clinical practice is essential. While there have been great strides in ensuring that babies born with congenital heart defects (CHD) are identified and repaired, we know that there are lifelong implications for those with CHDs that require continued follow-up and treatment. As the proportion of those with CHDs as adults continues to outpace the pediatric population, we urge... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

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4 up votes
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Goal 3: Advance Translational Research

Risk Mitigation of Implantable Cardiovascular Devices

There is a serious need to improve implantable cardiovascular devices to eliminate, or at least substantially reduce, the risk of serious adverse events from occurring to more effectively treat patients.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Cardiovascular devices would be more widely used to treat such cardiovascular diseases as heart failure, coronary artery disease, valvular disease and, therefore, have a greater public health benefit. Furthermore, costs associated with treating the serious adverse events (e.g. hospitalizations, therapeutics, etc.) would decrease.

Feasibility and challenges of addressing this CQ or CC

Technologies such as surface coatings and topographies as well as evolved design tools are under development already or are being used to mitigate the risks of devices currently being used or under development. A more concerted effort to do this would almost certainly help to substantially reduce the risks further, especially over the next 5-10 years.
Despite the widespread and growing use of implantable cardiovascular devices such as ventricular assist devices, stents, and prosthetic heart valves, substantial serious adverse events such as infections, neurological events, and bleeding limits the efficacy and use of the devices. Scientific and technological breakthroughs in such areas as biomaterials, design tools, coatings, and concomitant pharmacologic therapy are needed to address this challenge.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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9 up votes
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Goal 3: Advance Translational Research

Technologies for Ex-Vivo Cardiac Repair

What is needed to develop the technologies that will allow reparative interventions to be performed on excised natural hearts that have been overhauled ex vivo and replanted?

 

This will involve keeping the myocardium alive and sterile for extended periods that are long enough to complete the interventions while being able to also perform the necessary reparative interventions.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

The long-term impact would be to alleviate the need for permanent circulatory support devices or transplants by providing a means for hearts to be repaired while patients are temporarily supported using total artificial hearts. The immediate impact of developing the technologies to do this would be that the necessary interventions for ex-vivo cardiac repair could be developed and tested leading to a new therapy.

Feasibility and challenges of addressing this CQ or CC

A very basic foundation for this already exists. That foundation is an "Organ Care System" currently used in the UK to keep hearts functioning, not simply preserved, until the time of transplant for up to 12 hours. A timeframe of 5-10 years to extend the duration and the function of such a system for the stated purposes would seem feasible.
Repair and recovery of the heart is the currently limited to in vivo therapies. With the availability of artificial hearts and with the proper technologies available, the excised natural hearts from these patients could be overhauled ex vivo and re-implanted. Ideally, the overhaul would allow a way for various reparative interventions to be performed on the excised heart that would help to return it to a healthy functioning state before re-implantation. Such reparative interventions might include, but would not be limited to, surgical repair, adjunctive cell therapy, and stimulated exercise of the myocardium to influence reverse remodeling.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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Goal 3: Advance Translational Research

Obesity in special needs populations: Congenital heart disease

What are effective prevention and treatment strategies for populations with special needs, such as those with congenital heart disease, Down syndrome and preterm-born, to maintain a healthy weight?

Are there successful strategies derived from "normal" populations that could be effectively applied to these populations?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Children and individuals with special health conditions or needs are often excluded from participating in obesity treatment and prevention studies at the individual, group and community level. By answering this question, we would anticipate improving health, reducing future CV risks, increasing quality of life and decreasing already substantial healthcare costs in special needs populations.

Feasibility and challenges of addressing this CQ or CC
  1. We are beginning to understand which strategies appear effective in healthy overweight/obese populations, which could be leveraged for studies and interventions in special populations. 2. Adequate populations exist to address this CC: There are now more adults than children living with congenital heart disease, nearly 50% overweight or obese. Among these, individuals with Down syndrome are disproportionately overweight and have metabolic dysfunction. Preterm-born adults are more likely to be overweight/obese, have increased BP and other CV risks compared to term-born adults. 3. The Research Plan for Down Syndrome (NICHD) lists "obesity" in its short term research objectives.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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Goal 3: Advance Translational Research

Heart rate regulation as a therapeutic goal

Heart rate regulation is emerging as an effective treatment for heart failure and angina. However a critical challenge in the development of new therapeutics is the paucity of information about molecular and cellular determinants of heart rate.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

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Goal 3: Advance Translational Research

Exploring Future Cardiovascular Medicine: Heart Precursors Directed from Human Embryonic Stem Cells for Myocardium Regeneration

Cardiovascular disease (CVD) is a major health problem and the leading cause of death in the Western world. Currently, there is no treatment option or compound drug of molecular entity that can change the prognosis of CVD.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

The human stem cell is emerging as a new type of pharmacologic agent of cellular entity that is much more complex in structure, function, and activity than the conventional drug of molecular entity, which is usually comprised of simple chemicals or compounds. Since the etiologies of most diseases that involve both molecular and cellular processes are much more complex than simple chemicals or molecules, conventional chemical drugs are often severely limited by the molecular entity of the compound that usually targets or blocks certain pathological molecular pathways, which would otherwise be harmful to common molecular pathways shared in normal cellular processes of vital tissues and organs, thus, cause severe toxic side effects that may outweigh the benefits. For instance, a drug for weight loss may cause severe damage to the heart. In addition, the therapeutic effects of conventional drugs of molecular entity provide only temporary or short-term symptomatic relief but cannot change the prognosis of disease. As a result, millions of molecular leads generated in mainstream of biomedical research from animal studies and studies of other lower organisms have vanished before even reach clinical trials, or for a few lucky ones, in clinical trials. In the last few decades, despite of many animal leads, no drug of molecular entity has ever been approved by FDA as a new treatment for heart disease and failure for humans.

Feasibility and challenges of addressing this CQ or CC

Opportunity: In contrast, the human stem cell has the potential for human tissue and function restoration that the conventional drug of molecular entity lacks. The ability of a human stem cell, by definition, to both self-renew and differentiation makes it a practically inexhaustible source of replacement cells for many devastating or fatal diseases that have been considered as incurable, such as neurodegenerative diseases and heart diseases. The pharmacologic activity of human stem cells is measured by their extraordinary cellular ability to regenerate the tissue or organ that has been damaged or lost, such as the heart in the case of human cardiac stem cells. Therefore, the pharmacologic utility of human stem cells cannot be satisfied only by their chaperone activity, if any, to produce trophic or protective molecules to rescue existing endogenous host cells that can simply be accomplished by a drug of molecular entity. The embryo-originated human embryonic stem cells (hESC) are not only pluripotent, but also incredibly stable and positive, proffering unique revenue to generate a large supply of cardiac lineage-committed stem/precursor/progenitor cells as well as functional cardiomyocytes as adequate human myocardial grafts for cell-based therapy. Currently, the hESC cardiomyocyte therapy derivatives provide the only available human cell sources with adequate capacity to regenerate the contractile heart muscles, vital for heart repair in the clinical setting.

Name of idea submitter and other team members who worked on this idea Xuejun Parsons

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Goal 3: Advance Translational Research

Deriving Cardiac Elements from Pluripotent Human embryonic Stem Cells for Heart Reconstitution

to date, the existing markets lack a clinically-suitable human cardiomyocyte source with adequate myocardium regenerative potential, which has been the major setback in developing safe and effective cell-based therapies for regenerating the damaged human heart in cardiovascular disease.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Given the limited capacity of the heart for self-repair or renewal, cell-based therapy represents a promising therapeutic approach closest to provide a cure to restore normal heart tissue and function for CVD. There is no evidence that adult stem/precursor/progenitor cells derived from mature tissues, such as bone marrow, cord blood, umbilical cord, mesenchymal stem cells, patients’ heart tissue, placenta, or fat tissue, are able to give rise to the contractile heart muscle cells following transplantation into the heart. Despite numerous reports about cell populations expressing stem/precursor/progenitor cell markers identified in the adult hearts, the minuscule quantities and growing evidences indicating that they are not genuine heart cells and that they give rise predominantly to non-functional smooth muscle cells rather than functional contractile cardiomyocytes have caused skepticism if they can potentially be harnessed for cardiac repair. In recent years, reprogrammed or trans-differentiated adult cells, as a result of being backed by excess sum of government and private funding, have been rekindled as the adult alternates. However, major drawbacks such as abnormal gene expression, accelerated aging, immune rejection, not graftable, and extremely low efficiencies, have severely impaired the utility of reprogrammed or trans-differentiated somatic cells as viable therapeutic approaches.

Feasibility and challenges of addressing this CQ or CC

Opportunity: Derivation of pluripotent human embryonic stem cells (hESCs) from the IVF leftover embryos has brought a new era of cellular medicine for the heart. The intrinsic ability of a hESC for both unlimited self-renewal and differentiation into clinically-relevant lineages makes it a practically inexhaustible source of replacement cells for human tissue and function restoration. Therefore, it has been regarded as an ideal source to provide a large supply of functional human cells to heal the damaged or lost tissues that have naturally limited capacity for renewal, such as the human heart and the human brain. Although a vast sum of NHLBI funding has been spent on looking for adult alternates, such as reprogramming and trans-differentiation of fibroblasts or mature tissues, so far, only human cardiac stem/precursor/progenitor cells derived from embryo-originated hESCs have shown such cellular pharmacologic utility and capacity adequate for myocardium regeneration in pharmaceutical development of stem cell therapy for the damaged human heart.

Name of idea submitter and other team members who worked on this idea Xuejun Parsons

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