Featured Research

from universities, journals, and other organizations

Molecular 'cocktail' transforms skin cells into beating heart cells

Date:
February 20, 2014
Source:
Gladstone Institutes
Summary:
A new method has been devised that allows for the more efficient -- and, importantly, more complete -- reprogramming of skin cells into cells that are virtually indistinguishable from heart muscle cells. These findings, based on animal models, offer new-found optimism in the hunt for a way to regenerate muscle lost in a heart attack. Heart disease is the world's leading cause of death, but recent advances in science and medicine have improved the chances of surviving a heart attack. In the United States alone, nearly 1 million people have survived an attack, but are living with heart failure—a chronic condition in which the heart, having lost muscle during the attack, does not beat at full capacity. So, scientists have begun to look toward cellular reprogramming as a way to regenerate this damaged heart muscle.

These beating heart cells have been reprogrammed from skin cells using a combination of a chemical cocktail and just one genetic factor (Oct. 4). Reducing scientists' reliance on gene-based reprogramming approaches paves the way for pharmaceutical-based approaches that could more easily translate into successful therapies.
Credit: Haixia Wang/Gladstone Institutes

The power of regenerative medicine appears to have turned science fiction into scientific reality -- by allowing scientists to transform skin cells into cells that closely resemble beating heart cells. However, the methods required are complex, and the transformation is often incomplete. But now, scientists at the Gladstone Institutes have devised a new method that allows for the more efficient -- and, importantly, more complete -- reprogramming of skin cells into cells that are virtually indistinguishable from heart muscle cells. These findings, based on animal models and described in the latest issue of Cell Reports, offer new-found optimism in the hunt for a way to regenerate muscle lost in a heart attack.

Heart disease is the world's leading cause of death, but recent advances in science and medicine have improved the chances of surviving a heart attack. In the United States alone, nearly 1 million people have survived an attack, but are living with heart failure -- a chronic condition in which the heart, having lost muscle during the attack, does not beat at full capacity. So, scientists have begun to look toward cellular reprogramming as a way to regenerate this damaged heart muscle.

The reprogramming of skin cells into heart cells, an approach pioneered by Gladstone Investigator, Deepak Srivastava, MD, has required the insertion of several genetic factors to spur the reprogramming process. However, scientists have recognized potential problems with scaling this gene-based method into successful therapies. So some experts, including Gladstone Senior Investigator Sheng Ding, PhD, have taken a somewhat different approach.

"Scientists have previously shown that the insertion of between four and seven genetic factors can result in a skin cell being directly reprogrammed into a beating heart cell," explained Dr. Ding, the paper's senior author and a professor of pharmaceutical chemistry at UCSF, with which Gladstone is affiliated. "But in my lab, we set out to see if we could perform a similar transformation by eliminating -- or at least reducing -- the reliance on this type of genetic manipulation."

To that effect, the research team used skin cells extracted from adult mice to screen for chemical compounds, so-called 'small molecules,' that could replace the genetic factors. Dr. Ding and his research team have previously harnessed the power of small molecules to reprogram skin cells into neurons and, more recently, insulin-producing pancreas cells. They reasoned that a similar technique could be used to do the same with heart cells.

"After testing various combinations of small molecules, we narrowed down the list to a four-molecule 'cocktail,' which we called SPCF, that could guide the skin cells into becoming more like heart cells," said Gladstone Postdoctoral Scholar Haixia Wang, PhD, the paper's lead author. "These newly reprogramed cells exhibited some of the twitching and contracting normally seen in mature heart cells, but the transformation wasn't entirely complete."

So, Drs. Ding and Wang decided to add one genetic factor, called Oct4, to the small molecule cocktail. And by doing so, the research team was able to generate a completely reprogrammed beating heart cell.

"Once we added Oct4 to the mix, we observed clusters of contracting cells after a period of just 20 days," explained Dr. Ding. "Remarkably, additional analysis revealed that these cells showed the same patterns of gene activation and electric signaling patterns normally seen in the ventricles of the heart."

Dr. Ding and his team believe that these results may point to a more desirable method for reprogramming, as ventricular heart cells are the type of cells typically lost during a heart attack. These findings give the team newfound optimism that the research is well on its way towards an entirely pharmaceutical-based method to regrow heart muscle.

"The fact that the combination of Oct4 and small molecules appears to generate beating heart cells in an accelerated fashion is encouraging," said Joseph Wu, MD, PhD, Director of the Stanford Cardiovascular Institute, who was not involved in this study. "Future advances by Dr. Ding and others will likely focus on improving the efficiency of conversion as well as duplicating the data in adult human cells."


Story Source:

The above story is based on materials provided by Gladstone Institutes. Note: Materials may be edited for content and length.


Journal Reference:

  1. Haixia Wang, Nan Cao, C. Ian Spencer, Baoming Nie, Tianhua Ma, Tao Xu, Yu Zhang, Xiaojing Wang, Deepak Srivastava, Sheng Ding. Small Molecules Enable Cardiac Reprogramming of Mouse Fibroblasts with a Single Factor, Oct4. Cell Reports, February 2014 DOI: 10.1016/j.celrep.2014.01.038

Cite This Page:

Gladstone Institutes. "Molecular 'cocktail' transforms skin cells into beating heart cells." ScienceDaily. ScienceDaily, 20 February 2014. <www.sciencedaily.com/releases/2014/02/140220132202.htm>.
Gladstone Institutes. (2014, February 20). Molecular 'cocktail' transforms skin cells into beating heart cells. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2014/02/140220132202.htm
Gladstone Institutes. "Molecular 'cocktail' transforms skin cells into beating heart cells." ScienceDaily. www.sciencedaily.com/releases/2014/02/140220132202.htm (accessed July 29, 2014).

Share This




More Health & Medicine News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Two Americans Contract Ebola in Liberia

Two Americans Contract Ebola in Liberia

Reuters - US Online Video (July 28, 2014) Two American aid workers in Liberia test positive for Ebola while working to combat the deadliest outbreak of the virus ever. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins