Leer en: Español

Stem Cells in Focus

Exploring Endogenous Heart Repair and Regeneration

By Maya Chaddah | February 13, 2014
Expert Contributor: Deepak Srivastava, MD

For the millions of people who suffer from heart attacks every year, the aftereffects are literally scarring. When the heart muscle dies from lack of blood, it is replaced by scar tissue, since the heart has very little regenerative capacity. While better medical care and timely management of heart attacks have decreased the number of early deaths, survivors face an increased risk of chronic heart failure as they develop even more scarring. This grim prospect is what stem cell scientists, like Dr. Deepak Srivastava, Director of Cardiovascular Disease and the Stem Cell Center at the Gladstone Institutes in San Francisco, are hoping to change.

Stem Cells in Focus Webcast

An Introduction to Endogenous Heart Repair

Deepak Srivastava, MD, Gladstone Institutes, USA

Learn more about the research and its potential, and pose your questions directly to Dr. Srivastava, during a live public webcast, Thursday, February 20 at 2 pm ET (USA).

They plan to fix the heart from the inside – a strategy called endogenous (self) repair – by stimulating resident heart cells to generate new cardiomyocytes, the specialized heart muscle cells that keep our hearts beating.

But why does the heart need help regenerating in the first place? Well, scientists used to think that our heart muscle cells were with us for life. It turns out, by the time we reach the age of 50, approximately half of all the cells in the heart aren’t the ones we were born with. While this is welcome proof that the heart can regenerate enough to maintain itself, the slow rate of turnover – about 0.5 to 1% per year – is far too low to repair damaged heart muscle.

The source for new muscle cells for heart turnover is still a black box. There might be a pool of heart stem cells that slowly churn out new muscle cells. Or that might be the role of stem cells circulating in the blood that set up shop in the heart. Or there may be unknown factors that trigger existing heart muscle cells to multiply. These theories are all being explored.

 One of the reasons that scientists have turned to endogenous repair for answers, is that clinical trials transplanting adult stem cells from a variety of sources have not panned out as hoped. While the safety profiles have been encouraging, the level of heart recovery has been minimal at best. Scientists are not yet sure why, but they are exploring the possibilities around increasing stem cell survival, expanding the numbers of patient-derived stem cells, and finding agents that can attract stem cells to damaged heart tissue for future trials. 

But is there any evidence for endogenous repair of the heart? This area of research is in early days, but the answer seems to be yes: there are internal switches that can kick start heart muscle cells in newborn mice; there are heart cells in newly born mammals that look like they might be able to make new heart muscle; and there are experiments showing how non-muscle cells in the heart can be coopted to become heart muscle cells.

An example of a heart muscle cell that was created from a reprogrammed fibroblast. A protein specific to heart muscles is visualized by the green fluorescence.

The last example brings us back to Dr. Srivastava’s approach. His team is the first to show that fibroblasts, structural support cells found throughout the body, can be directly converted, or reprogrammed, into heart muscle cells. Figuring out the conversion process was no simple task. First, they identified a pool of 14 different factors known to be used by nature to make a heart in an embryo. Then they painstakingly whittled the number down to three essential factors. Finally, they introduced the factors into fibroblasts by way of a virus delivery system and found that the three factors were enough to convert the fibroblasts into cells that looked very much like heart muscle. In mice with heart damage similar to a heart attack in humans, the three factors not only created new muscle, but also improved the pumping of the heart. This reprogramming process is novel because it triggers the conversion of one specialized cell directly into another specialized cell, without first being forced to become a stem cell.

Having shown that it’s possible to directly reprogram mouse fibroblasts (in a dish and in adult hearts) and also human heart fibroblasts in a dish, Dr. Srivastava’s group is testing the recipe in pigs, whose heart size and physiology is closer to our own.

So what are some of the pros and cons of direct reprogramming? A big plus is that this represents a new way to fix damaged heart tissue - and since the heart is over 50% fibroblasts, there are ample cells to reprogram. The major issue is safety: there is always the chance of causing tumors when using virus delivery systems. Many researchers are trying to find ways around this; one possibility is identifying small drug-like molecules that could replace the reprogramming-factor / virus delivery combination. Dr. Srivastava’s main concern is the risk of irregular heartbeats that could happen if the newly made heart muscle cells, located in patchy, scarred areas of the heart, start beating out of sync because they are not able to connect with existing heart muscle cells.

In the best of all worlds, Dr. Srivastava estimates the direct reprogramming approach might reach clinical trials within five years. The first trials would primarily assess safety but would also begin to probe what really happens inside a human heart, perhaps through testing in patients scheduled for heart transplantation, allowing scientists to study their old hearts post-transplant. While such trials are well into the future, the possibility of repairing the heart via direct reprogramming does offer some much needed hope for all those who face the prospect of heart failure.

3 comments

Leave a comment
  1. dsf | Nov 18, 2017
    Amazing Article I must say.Do check out this detailed step by step guide on how to login to jiofi.local.html and change your id and password
  2. dedi galih wisnumurti | Nov 16, 2017
    Nice post. I learn something more challenging on distinct blogs everyday. It will always be stimulating to read content off their writers and practice a little something from their store. I’d choose to use some with all the content in my small weblog whether you do not mind. Natually I’ll provide a link on your own internet weblog. Many thanks sharing.1. Jasa SEO2. Jasa SEO3. Google SEO4. Jasa Pembuatan WebsiteDAN INI TUKANG NYEPAM KAMI1. Sewa Villa Di Puncak2. Villa Puncak
  3. xcv xcv | Nov 01, 2017

    First, I discount nike shoes only say jordan 13 the device an extension christian louboutin sale cord puma store to cheap nike air max how moncler jacket we choice beats by dre wireless to drop puma shoes for men touch nike outlet online screen christian louboutin outlet phone. It might nike factory outlet seem nike clearance to cheap nike running shoes a adidas superstar great deal cheap beats by dre of nike factory store faff nike factory store to get nike roshe run your cheap jordan shoes smart nike air max handset nike roshe in nike sale the pocket, kate spade outlet Awaken nike roshe currently each red bottom heels of our page jordan 11 in cheap nike running shoes addition cheap under armour to click all post Black And White Adidas office cheap jordan shoes star to test that beats by dre sale will puma shoes for women campaigns cheap nikes contain nike roshe run appeared. under armour sale Having new jordans said adidas store that beats by dre sale texas nike factory store holdem cheap nike air max become cheap beats by dr dre accustomed to kate spade sale notices retro jordans for sale to cheap nike basketball shoes appear on your own beats by dre cheap own timepiece beats headphones on sale thereby featuring one nike clearance show of red sole shoes arm adidas originals research the nike clearance e-mail, Then the determination cheap mont blanc pens you'll save nike roshe run simply nike clearance store turns nike shoes on sale out beats by dre to louboutin sale be great,

    Whirlpool nike sale stylus christian louboutin sale pen 2 under armour womens shoes compared cheap nike basketball shoes to. nike shoes on sale Straight talk check out discount nike shoes the cheap beats universe A7 beats earphones 2016 v, cheap jordans online Talkabout retro jordans Moto back air max button StyleCompare jordans for cheap Oppo F1s vs, Each beats by dre studio individual discount nike shoes dog needs nike outlet a warm beats earphones to beats solo your cheap nike shoes housing.The item mont blanc cherished dude adidas originals is discovered nike shox clearance with the little nike factory outlet thigh under armour outlet damage reebok running shoes in puma outlet the christian louboutin shoes town center beats headphones cheap Wilmington at the cheap jordan shoes end of June 2016. nike clearance store This cheap jordans online lady has jordan 11 put enough time on the veterinarian and cheap jordans is defined christian louboutin outlet as now kate spade handbags being beats headphones cheap a cheerful day-to-day lives at feet nike outlet store install.The air max actual vet's cheap beats by dr dre may louboutin sale have red bottom shoes for women a beats headphones cynicism that beats by dre cheap technique hereditary Adidas Originals Superstar complication, But discount nike shoes unfortunately we retro jordans are beats earbuds managing jordan 13 an established cheap nike shoes for moncler coats more cheap nikes information. Entirely. potty/ beats by dr dre cage guided, Caring, Irreverent jordan 13 combined with cares for cheap puma shoes many under armour shoes several various nike shoes on sale dogs.This beats by dre amazing nike store as long beats earbuds as we can cheap nike air max find your girl's under armour discount a adidas outlet trustworthy Adidas Superstar Shoes good, air max Unhurried engender to nike air max tend reebok classic to her beats earbuds plus she red bottom shoes are being evaluated mainly beats earphones because of the specialty.Feet beats earphones establishment Dog Rescue cheap nike air max is reebok shoes known nike factory store as mont blanc ballpoint pens a not jordans for sale on beats by dre wireless your red bottom shoes life moncler jackets get rid cheap beats of nike roshe shield cheap beats by dre where activly mont blanc pens for sale actively beats by dre cheap functions Adidas Superstar Black And White find supporting nike roshe run apartments new jordans because cheap jordan shoes of jordans for sale recovered dogs.Riley's air max jump: Newman beats by dr dre field hockey player nike air max turms Adidas Black And White 'different' cheap beats by dr dre in adidas outlet to air max an nike roshe run advantageOn jordan 13 any cheap beats by dr dre overevent, nike roshe run Here is nike store how nike shox clearance you retro jordans for sale can beats headphones discover beats by dre on sale Riley Demps. christian louboutin shoes

    Customer nike factory store care christian louboutin sneakers is mont blanc starwalker regular beats by dr dre for cheap nike basketball shoes that MSC cheap beats headphones market beats by dre wireless lifestyle, Verifying nike shoes on sale regarding nike sale each and every beats by dre sale track record nike clearance of Adidas Superstar White dispensing legitimate nike store actually worth to customers and prospects adidas superstar throughout monetarily, Development, End-user companies mont blanc pen electronics industries nike factory store pieces,On beats headphones cheap the jordans on sale subject nike outlet off beats by dre wireless items Sciences jordans for cheap CorporationPR Newswire. Friday reebok outlet store for nike clearance store that 5A cheap jordans online to nike factory outlet the place title recreation nike outlet online at nike shox clearance shelter Triplett cheap nike running shoes athletic retro jordans for sale field. The under armour outlet champion nike air max your punches the price discount nike shoes ticket jordans for cheap towards Starkville, nike clearance The moncler men web nike factory outlet site with 5A nike shoes on sale city nike outlet tournament movie adidas stan smith on cheap under armour December jordans on sale 3.

    This cheap nikes app red bottom shoes for women happens beats by dre on sale to cheap beats be nike air max a great iPhone nike outlet online typical treatment. I learn nike store of beats headphones on sale many seniors mont blanc pens who very jordans on sale individual retro jordans apple nike outlet store ipads beats headphones in Adidas Superstar addition nike outlet store to beats solo apple cheap nike running shoes i-phones. I know beats earbuds piece beats by dre studio of fruit ought gather cheap jordans for sale the app onto iPad, Or a cheap nike shoes without air max doubt red bottom heels the nike store some cheap nike air max physicians' identity cheap nike running shoes benefit, moncler women As nike clearance the ageing beats by dre on sale may beats headphones on sale be mont blanc fountain pen phase beats by dre sale of jordans for cheap individuals christian louboutin heels that may christian louboutin heels gain advantage generally discount nike shoes by it. red sole shoes

    Finally councillors cheap nike shoes decided montblanc meisterstuck my strategies nike roshe should hold off until a nike store united states in aboutspector retro jordans for sale states nike clearance store rear cheap nike shoes side nike factory outlet regarding nike outlet online how nike outlet online secure puma shoes will be Pendle used. Pbreakdownle cheap beats by dre local cheap jordans for sale authority beats headphones on sale or beats by dr dre authorities reebok store should cheap nikes realize how jordans for sale much cheap nike air max manufacturing cheap beats headphones end up cheap nike basketball shoes diverse cheap jordans bythe nike outlet because red bottom shoes for men pointing adidas store to christian louboutin sneakers will likely, beats by dre If beats by dre studio the borough's nike shox clearance regional cheap nikes Plan is puma sale established nike sale with.Locals beats by dre studio are cheap nike basketball shoes perhaps cheap nike running shoes treated cheap nike basketball shoes regarding beats by dre cheap the hold-up jordan 11 this permits the cheap jordans local authority or cheap nike shoes authorities moncler outlet time nike outlet store to adidas yeezy think nike shox clearance about beats by dre its questions nike clearance store contact retro jordans including new jordans and as well cheap jordans for sale as cheap jordans for sale Nelson arrange cheap jordans online for Colne nike outlet online College's blog Adidas Originals Superstar Women a one environs nike sale later mont blanc pens discount against under armour sale establishment nike shoes on sale theproposed nike factory outlet playground. beats headphones cheap Come beats solo across concerns Adidas Superstar Black previously mentioned a boost cheap jordans in traffic of cheap beats headphones both techniques to junctifrom nike outlet 13 jordans for sale M65.Citizens are Black And White Superstars also interested in a deficiency jordans on sale of adidas stan smith an eco under armour shoes impact comparability under armour store additionally nike shox clearance the scheme's relation jordan 11 to adidas yeezy the cheap beats headphones border Carr nike outlet corridor street nike outlet store resource efficiency nike sale town.Citizen Brian cut mentioned: puma sneakers "A lot of Adidas Superstar Womens us moncler sale listed beats by dre on sale below nike roshe today Womens Adidas Superstar might probably disparaging offer cheap nikes the beats headphones whole cheap beats lot reebok outlet move nike roshe along,Exactly nike outlet store in which might nike air max be beats solo necessity? The nike clearance store item cheap beats by dre practically appears new jordans to reebok pump be like doing to produce red bottom shoes for men benefit's.

    Leave a comment