Navigation Links
Injection Reverses Heart-Attack Damage

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:

    Rob Graham
    Children's Hospital Boston

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:
(Date:11/24/2015)... 2015  DILON Diagnostics and GE Healthcare are pleased ... DILON to distribute GE,s Discovery NM750b Molecular Breast Imaging ... this distribution agreement will provide Dilon,s experienced distribution network ... and is considered an initial step in an ongoing ... clinicians and their patients. --> ...
(Date:11/24/2015)... November 24, 2015 Sectra (STO: ... has entered into a multi-year agreement to deploy ... investment will provide the Breast Center a future-proof platform ... (STO: SECT B) announces that Breast Center of ... deploy Breast Imaging PACS in its two freestanding imaging ...
(Date:11/24/2015)... FRAMINGHAM, Mass. , Nov. 24, 2015   ... leading innovator of less-invasive, miniaturized circulatory support technologies that ... announced that President and Chief Executive Officer Doug ... Jaffray 27 th Annual Healthcare Conference on December ... being held December 1-2 in New York ...
Breaking Medicine Technology:
(Date:11/25/2015)... WASHINGTON, D.C. (PRWEB) , ... November 25, 2015 , ... ... driving fatalities on our nation’s roadways has dropped below 10,000 for the first time ... to 10,076 in 2013. , According to data released by the National Highway Traffic ...
(Date:11/25/2015)... ... November 25, 2015 , ... An ... is resulting in a way for homeless people to have a more dignified ... a new initiative whereby they are repurposing plastic bags into sleeping mats for ...
(Date:11/25/2015)... ... November 25, 2015 , ... ... offering lower prices in an early celebration of the early holiday shopping season. ... of $29.95 each (normally $33.95 ea). Black Friday promotional pricing is in addition ...
(Date:11/24/2015)... ... November 24, 2015 , ... Young patients with a ... Dr. Angela Wolfman and Dr. Kedar S. Lele, who are pediatric dentists in ... and fillings, the WaterLase iPlus 2.0™ system causes minimal discomfort and bleeding to the ...
(Date:11/24/2015)... ... 24, 2015 , ... DMG Productions announced that they will feature Aphria, Inc., ... via Discovery Channel. Dates and show times TBA. , Aphria, Inc., is a publicly ... of producing and supplying medical marijuana pursuant to the Marijuana for Medical Purposes Regulations ...
Breaking Medicine News(10 mins):