Stem cell stories that caught our eye: heart repair, a culprit in schizophrenia, 3-parent embryos and funding for young scientists

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Chemicals give stem cells heart.  Coaxing stem cells into improving the function of failing hearts has proven quite difficult. Many trials have used a type of stem cell found in fat and bone marrow, called mesenchymal stem cells, to release factors believed to reduce scarring after a heart attack and improve the growth of new blood vessels to nourish the damaged area. But they have produced spotty and only modest positive results. CIRM funds a team at Capricor that uses related cells, but retrieved from heart tissue and believed to release factors that are more efficient in fostering repair—the results are still pending.

Get-Over-Heartbreak-Step-08 This week a Belgian company, using technology developed by the Mayo Clinic in Minnesota, announced positive results for a third option. They start with the stem cells from bone marrow, but in the lab treat them with a cocktail of chemicals that take them part way down the path to becoming heart muscle—into cells called cardiac progenitors. Having shown safety and initial signs of benefit in Phase 1 and 2 trials in Europe, the company Celyad launched the first part of a Phase 3 trial in 2012 and released the results this week.

The company’s research team found that, as with many breakthrough therapies, the most important aspect of early trials is defining which patients are most likely to benefit. The results did not show a benefit for the entire patient group lumped together, but did show significant gain for the 60 percent who fit a certain profile of symptoms at the start of the study. Twin Cities Business wrote about the research that originated in its home state, quoting the lead researcher with OLV Hospital in Belgium, Jozef Bartunek:

 “The results seen for a large clinically relevant number of the patients are groundbreaking,” adding that the results would direct the selection of patients for the second part of the trial to be conducted in the U.S.

The fundamental work done by researchers at Mayo discovered the mechanisms that drive an embryonic stem cell to become heart cells and used that information to develop the cocktail of chemicals that can turn ordinary adult stem cells into cardiac progenitors.

 

Stem cell model fingers culprit in brain. We were all taught the dogma about the path from genes to our tissues: DNA to RNA to protein. And we learned that two types of RNA did the heavy lifting in this transition from genetic recipe to functioning tissue. But RNAs have turned out to be a much more complex family of genetic players, with several types regulating genes rather than coding for any specific function. Some of the most active of these are the micoRNAs with more than 2,000 identified.

A CIRM-funded team at the Salk Institute in La Jolla has fingered one microRNA, miR-19, as playing a role in the faulty wiring seen among nerves in patients with schizophrenia. We always have a few nerve progenitor cells maturing into nerves. But the team found that when they altered the levels of miR-19 the new nerves did not migrate to where they were needed. So, the researchers made iPS type stem cells from patients with schizophrenia, matured them into nerves and looked at miR-19 levels and found them elevated. They also showed the nerve cells did not migrate properly.

 “This is one of the first links between an individual microRNA and a specific process in the brain or a brain disorder,” said senior author Rusty Gage, in an institute press release posted by trueviralnews.

mir19-schizophrenia-neurosciencenews

Over expressing the microRNA miR-19 resulted in new nerves migrating and branching abnormally (right) compared to untreated cells (left)

 

Profile of 3-parent pioneer.  No matter where you stand on the ethics of the “three-parent” fertilization technique that has been much in the news this year, you will enjoy reading Karen Weintraub’s well researched and well written piece about the leading pioneer in the field, Shoukhrat Mitalipov in STAT this morning.

 

Mitalipov-2

Pioneer Mitalipov

The technique focuses on the 37 genes that reside in our cells’ mitochondria rather than in the cells’ nucleus. We only inherit those genes from our moms because we only get the mitochondria in mom’s egg. So, when a woman has a disease-causing mutation in one of those genes, she could have a healthy child that mostly matched her genetic makeup if she could just swap out her mitochondria for someone else’s. That is exactly what the new technique accomplishes.

So far, it has only been tried in monkeys, the oldest of those offspring are now 7 but they are males. The first female is just 4 and since monkeys don’t reproduce until age 6 or 7, and the FDA wants to see how her babies fare, it will be some time before the procedure gets the green light to move forward in humans. None of the 3-parent monkeys show any health issues so far.

Karen’s piece paints a detailed account of the research’s protractors and detractors, as well putting a human face on the man leading the charge. As someone who reads regular posts from a cousin with a child struggling from “Mito” disease, I am rooting for this protagonist.

 

Funding challenge for young stem cell scientists.  A new study in the journal Cell Stem Cell quantifies a lament you hear anytime you are around young researchers, they have a hard time competing with older researchers in the field. The author of the report, Misty Heggeness from the National Institutes of Health, was quoted in news outlets including the San Diego Union Tribune and the blog Science 2.0 on a related issue that should set off alarm bells. If young people are not attracted to the field or fail to stay in the field, at the same time established scientists are nearing retirement age, we could end up with a gap in the research workforce in a few years.

 “From a policy and leadership perspective, one needs to understand what the near future year implications of an aging workforce are. If a system discourages younger cohorts from staying and is heavily composed of older cohorts who will exit the workforce in the near term, who will replace them?”

Part of the problem young researchers have seems to be baked into the current system. Young researchers compete fairly well with older ones on individual applications, but older researchers have the resources to file a lot more applications.  They have more personnel in their labs, freeing them up to write applications, and that personnel also produces the preliminary data that are often needed to even meet application requirements.

The Union Trib piece pointed out that older and younger stem cell scientists are both doing better with funding in California because of CIRM.

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