Navigation Links
Injection Reverses Heart-Attack Damage
Date:7/23/2009

Growth factor enhances heart regeneration, improves heart function without need for cardiac stem cells

BOSTON, July 23 /PRNewswire-USNewswire/ -- Injured heart tissue normally can't regrow, but researchers at Children's Hospital Boston have now laid the groundwork for regenerating heart tissue after a heart attack, in patients with heart failure, or in children with congenital heart defects. In the July 24 issue of Cell, they show that a growth factor called neuregulin1 (NRG1), which is involved in the initial development of the heart and nervous system, can spur heart-muscle growth and recovery of cardiac function when injected systemically into animals after a heart attack.

After birth, heart-muscle cells (cardiomyocytes) normally withdraw from the cell cycle - meaning they stop dividing and proliferating. But the researchers, led by Bernhard Kuhn, M.D., and Kevin Bersell of the Department of Cardiology at Children's, were able to restart the cell cycle with NRG1, stimulating cardiomyocytes to divide and make copies of themselves -- even though they are not stem cells.

"Although many efforts have focused on stem-cell based strategies, our work suggests that stem cells aren't required and that stimulating differentiated cardiomyocytes to proliferate may be a viable alternative," says Kuhn, the study's senior investigator and a practicing pediatric cardiologist at Children's since 2007.

When the team injected NRG1 into the peritoneal cavity of live mice after a heart attack, once daily for 12 weeks, heart regeneration was increased and pumping function (ejection fraction, assessed on echocardiograms) improved as compared with untreated controls. The NRG1-injected mice also lacked the left-ventricular dilation and cardiac hypertrophy that typify heart failure; both were seen in the controls.

When the researchers also stimulated production of a cellular receptor for NRG1, known as ErbB4, cardiomyocyte proliferation was further enhanced, demonstrating that NRG1 works by stimulating this receptor. They also identified the specific kinds of cardiomyocytes (mononucleated) that are most likely to respond to treatment.

In 2007, Kuhn and colleagues first demonstrated that the heart has dormant regenerative capacities that can be reawakened. Kuhn developed a sponge-like patch, soaked in a compound called periostin that is abundant in the developing fetal heart (and in injured skeletal muscle) but scarce in adult hearts. When the patch was placed over the site of cardiac injury in rats, it induced cardiomyocyte proliferation and improved heart function (Nature Medicine 2007; 13:962-9). Similar results were seen in larger animals, and periostin is now in preclinical development at Children's Hospital Boston for future application in human patients with heart failure.

The new work adds a second compound to the heart-regeneration toolbox, and reveals how both periostin and NRG1 work at the cellular and molecular level, an essential step in predicting possible side effects. Both compounds ultimately act on the same cellular pathway, Kuhn found.

"We applied periostin locally at the site of cardiac injury, but NRG1 works when given by systemic injection - a very promising result that suggests it may be feasible to use this in the clinic to treat heart failure," says Kuhn, who won a first prize Young Investigator Award, from the American College of Cardiology in 2007.

The study was funded by the Department of Cardiology at Children's Hospital Boston, the Charles Hood Foundation, and the American Heart Association.

Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, 12 members of the Institute of Medicine and 12 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 397-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about the hospital and its research visit: www.childrenshospital.org/newsroom.

    CONTACT:
    Rob Graham
    Children's Hospital Boston
    617-919-3110
    Media.Relations@childrens.harvard.edu



'/>"/>
SOURCE Children's Hospital of Boston
Copyright©2009 PR Newswire.
All rights reserved

Related medicine technology :

1. Phase III Clinical Trial in Newly Diagnosed Multiple Myeloma Stopped Early Due to Highly Significant Efficacy Advantage of VELCADE(R) (Bortezomib) for Injection Based Therapy Across All Endpoints
2. Study Shows Vasopressin Receptor Antagonist VAPRISOL(R) (Conivaptan Hydrochloride Injection) Significantly Increased Serum Sodium Concentration in Patients with Euvolemic & Hypervolemic Hyponatremia
3. Lilly Files for European Approval of ALIMTA(R) (pemetrexed for injection) for First-Line Treatment of Non-Small Cell Lung Cancer
4. Analysis Shows Vernakalant Hydrochloride Injection Increases Conversion to Normal Heart Rhythm in Acute Atrial Fibrillation Patients Treated Within 48 Hours of Onset
5. New Data to Support VELCADE(R) (Bortezomib) For Injection Based Therapies as Setting New Standards in The Care of Newly Diagnosed Patients With Multiple Myeloma
6. Isolagen Inc. Completes Injections of Isolagen Therapy(TM) in Phase III Wrinkle and Phase II Full Face Studies
7. FDA Advisory Committee Supports Efficacy and Safety of Zyprexa(R) Long-Acting Injection (LAI) for Schizophrenia Treatment
8. Millennium Expands VELCADE(R) (Bortezomib) For Injection Program In Non-Hodgkins Lymphoma
9. Inclusion of Six-Year Overall Survival Data in the Eloxatin(R) (oxaliplatin injection) Prescribing Information Granted FDA Priority Review
10. Circulation Publishes Data Showing KYNAPID(TM) (Vernakalant Hydrochloride) Injection Rapidly Converted Short-Duration Atrial Fibrillation to Sinus Rhythm
11. CorMatrix(R) Announces Intramyocardial Injection of Emulsified ECM Technology(TM) Demonstrates Enhanced Angiogenesis and Improved Cardiac Function in a Preclinical Model
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/27/2016)... 27, 2016 Amarantus BioScience Holdings, Inc. ... products for Regenerative Medicine, Neurology and Orphan Diseases, today announced that ... at two upcoming investor conferences: SeeThru Equity MicroCap ... New York City , NY When: ... Marcum MicroCap Conference   Where: Grand Hyatt Hotel, 109 ...
(Date:5/26/2016)... TARE (Transarterial Radio-embolization) Using ... and Overall Decreased Use of Hospital Resource ... specialist healthcare company, has today announced the publication ... of ISPOR (International Society for Pharmacoeconomics and Outcomes ... using yttrium-90 glass microspheres is associated with cost ...
(Date:5/25/2016)... -- According to a new market research ... by Therapeutic Area (Oncology, Cosmeceutical/Plastic Surgery), by Application (Drug ... Hospitals/ Clinics) - Forecast to 2021", published by MarketsandMarkets, ... the forecast period of 2016 to 2021. This market ... from USD 117.3 Million in 2016, at a CAGR ...
Breaking Medicine Technology:
(Date:5/27/2016)... Killeen, Texas (PRWEB) , ... May 27, 2016 , ... ... with satisfying Army body fat composition regulations. This is the first time that ... are normally screened at least every six months to ensure they meet the prescribed ...
(Date:5/27/2016)... , ... May 27, 2016 , ... ... scholarships to students studying complementary medicine. Allison Outerbridge is this year’s Life ... award on May 18 at the university’s Student Leadership Awards ceremony. , Outerbridge ...
(Date:5/26/2016)... ... May 26, 2016 , ... There are many ways to cook ... Council (NHDSC) suggests that Americans prefer their dogs straight off the grill. Of the ... is their favorite way to cook a hot dog, far outpacing other cooking methods ...
(Date:5/26/2016)... Missouri (PRWEB) , ... May 26, 2016 , ... ... quality and clinical outcomes, hosted members and suppliers for its inaugural Member Conference ... focus on their mission of elevating the operational health of America’s healthcare providers. ...
(Date:5/26/2016)... Washington, D.C. (PRWEB) , ... May 26, 2016 , ... ... the men and women who lost their lives in military battle for the country. ... discount cards in 2015 to provide more programs that empower independence for disabled military ...
Breaking Medicine News(10 mins):