Taking Steps Toward Personalized Heart Transplants

Over five million Americans have heart failure (HF), a condition in which the heart muscles become too weak to pump an adequate amount of blood, oxygen and nutrients to the body’s other organs. People with heart failure suffer from shortness of breath, chronic weakness and a fifty percent chance of dying within the first five years of diagnosis.

SystolicDiastolic_Heartfailure.5518685646fab

Heart failure weakens the heart’s ability to pump blood to the body.
Image credit: Fran Milner, http://www.franimation.com

Heart transplants: swapping one disease for another
The only true cure for heart failure is an organ transplant but donor organs are in limited supply. And those lucky enough to receive a transplant need to take life long immunosuppressive drugs to fight off organ rejection, which often leads to other serious health problems like risk of infection, high blood pressure, diabetes and kidney failure.

It’s not a pretty picture for patients and with a cost to the nation of $32 billion annually, heart failure affects us all.

In a recent Circulation Research journal article, a team at the Massachusetts General Hospital (MGH) Center for Regenerative Medicine (CRM) reported on an incremental yet important step toward an alternative approach to heart transplants: growing bioengineered hearts with a patient’s own stem cells.

Bioengineered hearts: been there, done that
Bioengineered hearts may sound far fetched but eight years have already passed since researchers showed it’s possible with animal models. In that 2008 study, scientists at the University of Minnesota soaked rat hearts in detergents that cleaned away all of the heart cells, leaving behind a scaffold of connective tissue that is secreted by the cells. They then “re-seeded” the scaffold with rat progenitor heart muscle cells. Incredibly, after 4 days in a bioreactor, the tissue began contracting. After 8 days, using electrical stimulation, the hearts could pump with measurable strength.

heartscaffold

Custom built bioreactor with a partially recellularized human whole-heart cardiac scaffold. Image credit: Bernhard Jank, MD, Ott Lab, CRM MGH

Harald Ott, the first author of that proof of concept study, now leads the MGH team in the current study. With an eye toward bringing this method to the clinic, Ott aimed to reproduce the rat studies using human cells and hearts. Specific consent was obtained to recover seventy-three human hearts donated after brain death or cardiac death and were determined to be unusable for clinical transplant.

Just as in the previous study, heart scaffolds were created by clearing away the cells from these organs. Half a billion human heart muscle cells, or cardiomyocytes, that had been grown from human induced pluripotent stem cells (iPS) were then injected into the scaffolds. At this early stage of research, the team did not attempt to reseed the entire heart but specifically focused on areas around the left ventricle – the heart chamber responsible for pumping oxygenated blood out to the rest of the body.

In order to recellularize the scaffold under conditions that resemble the contractions that actually occur in a human heart inside the body, pressure was rhythmically applied using a balloon inside the ventricle – watch it in action by downloading this video.

Screen Shot 2016-03-15 at 9.22.17 AM

Decellularized heart scaffold is injected with iPS heart muscle cells and incubated in a bioreactor to grow new heart muscle (Circ Res. 2016;118:56-72).

After incubating the heart for 14 days in a bioreactor, the team confirmed the cardiomyocytes had formed into functioning heart muscle, or myocardial, tissue that contracted upon electrical stimulation (watch the beating heart by downloading this video).

Looking ahead to a “grow yourself a new heart” future
These results set a course for a future in which scientists could grow a new, personalized heart for people with heart failure. Since the bioengineered heart would be built using iPS cells derived from the patient’s own skin or blood sample, this technique would likely get around the problems of organ rejection and the need for immunosuppressive drugs. Additional analysis in the current study also confirmed that the donor heart scaffold itself, which is void of cells, probably will not pose tissue rejection problems either.

The other key problem, a limited supply of donor hearts, was also addressed. Heart scaffolds donated after cardiac death performed just as well as those donated after brain death which would make this technique available to more patients waiting anxiously for a transplant.

The MGH team would be the first to tell you this “grow yourself a new heart” scenario is still off on the horizon. But as first author, Jacques Guyette, stated in a news release, there are milestones to reach along the way:

“Regenerating a whole heart is most certainly a long-term goal that is several years away, so we are currently working on engineering a functional myocardial [heart muscle tissue] patch that could replace cardiac tissue damaged due a heart attack or heart failure.”

Related Links:

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s