Stem cell stories that caught our eye: relief for jaw pain, vitamins for iPSCs and Alzheimer’s insights

Jaw bone stem cells may offer relief for suffers of painful joint disorder
An estimated 10 million people in the US – mostly women –  suffer from problems with their temporomandibular joint (TMJ) which sits between the jaw bone and skull. TMJ disorders can lead to a number of symptoms such as intense pain in the jaw, face and head; difficulty swallowing and talking; and dizziness.

ds00355_im00012_mcdc7_tmj_jpgThe TMJ is made up of fibrocartilage which, when healthy, acts as a cushion to enable a person to move their jaw smoothly. But this cartilage doesn’t have the capacity to heal or regenerate so treatments including surgery and pain killers only mask the symptoms without fixing the underlying damage of the joint.

Reporting this week in Nature Communications, researchers at Columbia University’s College of Dental Medicine identified stem cells within the TMJ that can form cartilage and bone – in cell culture studies as well as in animals. The research team further showed that the signaling activity of a protein called Wnt leads to a reduction of these fibrocartilage stem cells (FSCSs) in animals and as a result causes deterioration of cartilage. But injecting a known inhibitor of Wnt into the animals’ damaged TMJ spurred growth and healing of the joint.

The team is now in search of other Wnt inhibitors that could be used in a clinical setting. In a university press release, Jeremy Mao, a co-author on the paper, talked about the implications of these results:

“They suggest that molecular signals that govern stem cells may have therapeutic applications for cartilage and bone regeneration. Cartilage and certain bone defects are notoriously difficult to heal.”

Take your vitamins: good advice for people and iPS cells
From a young age, we’re repeatedly told how getting enough vitamins each day is important for a healthy life. Our bodies don’t produce these naturally occurring chemicals but they carry out critical biochemical activities to keep our cells and organs functioning properly.


Carrots: a great source of vitamin A. Image source: Wikimedia Commons

Well, it turns out that vitamins are also an important ingredient in stem cell research labs. Results published the Proceedings of the National Academy of Sciences (PNAS) this week by scientists in the UK and New Zealand show that vitamin A and C work together synergistically to improve the efficiency of reprogramming adult cells, like skin or blood, into the embryonic stem cell-like state of induced pluripotent stem cells (iPSCs).

By the time a stem cell has specialized into, let’s say, a skin cell, only skin cell-specific genes are active while others genes, like those needed for liver function, are shut down. Those non-skin genes are silenced through the attachment of chemical tags on the DNA, a process called methylation. It essentially provides the DNA with the means of maintaining a skin cell “memory”. To convert a skin cell back into a stem cell-like state, researchers in the lab must erase this “memory” by adding factors which demethylate, or remove the methylation tags on the silenced, non-skin related genes.

In the current research picked up by Science Daily, the researchers found that both vitamin A and C increase demethylation but in different ways. The study showed that vitamin A acts to increase the production of proteins that are important for demethylation while vitamin C acts to enhance the enzymatic activity of demethylation.

These insights may help add to the growing knowledge on how to most efficiently reprogram adult cells into iPSCs. And they may prove useful for a better understanding of certain cancers which contain cells that are essentially reprogrammed into a stem cell-like state.

New angles for dealing with the tangles in the Alzheimer’s brain
The memory loss and overall degradation of brain function seen in people with Alzheimer’s Disease (AD) is thought to be caused by the accumulation of amyloid and tau proteins which form plaques and tangles in the brain. These abnormal structures are toxic to brain cells and ultimately lead to cell death.

But other studies of post-mortem AD brains suggest a malfunction in endocytosis – a process of taking up and transporting proteins to different parts of the cell – may also play a role. While follow up studies corroborated this initial observation, they didn’t look at endocytosis in nerve cells so it remained unclear how much of a role it played in AD.

In a CIRM-funded study published this week in Cell Reports, UC San Diego researchers made nerve cells from human iPSCs and used the popular CRISPR and TALEN gene editing techniques to generate mutations seen in inherited forms of AD. One of those inherited mutations is in the PS1 gene which has been shown to play a role in transporting amyloid proteins in nerve cells. The research confirmed that this mutation as well as a mutation in the amyloid precursor protein (APP) led to a breakdown in the proper trafficking of APP within the mutated nerve cells. In fact, they found an accumulation of APP in a wrong area of the nerve cell. However, blocking the action of a protein called secretase that normally processes the APP protein helped restore proper protein transport. In a university press release, team leader Larry Goldstein, explained the importance of these findings:


Larry Goldstein.
Image: UCSD

“Our results further illuminate the complex processes involved in the degradation and decline of neurons, which is, of course, the essential characteristic and cause of AD. But beyond that, they point to a new target and therapy for a condition that currently has no proven treatment or cure.”



Stem cell stories that caught our eye: Designer bags from human skin, large-scale stem cell production, new look at fat stem cells

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.

Designer bags from human skin? I had to share a bizarre story I read this week about a UK fashion designer who is making a collection of luxury handbags from lab-grown human skin called Pure Human. What’s even weirder is that the human skin used was engineered to contain the genetic material or DNA of the famous fashion designer Alexander McQueen who passed away in 2010.

A prototype bag, made with pig skin, from Tina Gorjanc’s Pure Human collection (Credit: Tina Gorjanc)

A prototype bag, made with pig skin, from Tina Gorjanc’s Pure Human collection (Credit: Tina Gorjanc & Signals blog for caption)

I had to admit I cringed when I first read about it in CCRM’s Signals Blog, but now I am fascinated that someone is actually doing this and intrigued about the ethical conversations that this story will undoubtedly stir up.

While it isn’t possible to patent a person’s DNA, it is possible to patent a technology that uses human DNA and products made from that technology. According to Signals, “the aim of the collection is to highlight existing legal loopholes around ownership of a person’s DNA and to open the doors for tissue bioengineering into the world of fashion.”

The collection’s designer, Tina Gorjanc, explained her motivation behind Pure Human:


Tina Gorjanc

“My main goal was to show that it is possible to patent a process using human genetic information in a domain other than medicine. Biotechnology is happening at a really rapid pace and legislation has not kept up with it.”


She also sees her bags as an untapped resource in the global luxury goods market which is now apparently worth $1 trillion dollars.

“When it comes to bioengineering, people tend to skip the luxury goods market because they think it’s too shallow and not important, but if you look at it, it’s one of the biggest markets that we have – and one that is open to new technology.”

Imagine having the option to bypass animal leather products for engineered human skin-based products? But on the flip side, the author of the Signals blog, Jovana Drinjakovic, makes a great point at the end of her piece by saying: just because we can do this, does it mean we should?

Drinjakovic finishes her piece with a reality-check quote from Dr. Marc Jeschke, the leader of a burn research and skin regeneration lab in Toronto:

“We are trying to find a way to make skin that is functional and won’t be rejected after a transplant. But just to grow skin for fashion – I don’t think that’s very useful.”


Large-Scale Stem Cell Production in Texas. A nonprofit company in San Antonio, Texas, called BioBridge, has big plans to produce large amounts of clinical-grade stem cells for regenerative medicine purposes. The company recently received $7.8 million in funding from the Medical Technology Enterprise Consortium to pursue this effort.

BioBridge will work with GenCure, a subsidiary company, to develop the technology to manufacture different types of stem cells at a large scale. These stem cells will be clinical-grade, meaning that they can be used for cell therapy applications in patients. BioBridge’s goal is to provide enough stem cells for both academic researchers and companies who need more than their current lab resources can generate.

The CEO of GenCure, Becky Cap, explained the need for this type of large-scale stem cell manufacturing technology in an interview with Xconomy:

“The capabilities in this sector right now are at a scale that’s appropriate for bench research and some clinical research, depending on the indication and volume of cells we need. We’re talking about moving from hundreds of millions of cells to billions of cells. You need billions of cells to do tissue regeneration and scaffold reengineering.”

Two other companies with expertise in cell manufacturing, StemBioSys from San Antonio and RoosterBio in Maryland, will be working with BioBridge and GenCure over the next three years on specific projects. StemBioSys plans to develop materials that will be used to promote stem cell growth. RoosterBio will take stem cell culturing from small-scale petri dishes to large-scale bioreactors that can produce billions of cells.

It will be interesting to see how the BioBridge collaboration works out. Xconomy concluded:

“This sort of large-scale manufacturing is still years out. The results that come from the work will be incorporated into a contract manufacturing operation that BioBridge is opening within GenCure.”


A new way to look at fat stem cells. (By Todd Dubnicoff)

Human fat stem cells, scientifically known as human adipose stem cells (hASC), are an attractive cell source for regenerative medicine. Their low tendency to cause tissue rejection and their ability to transform into bone cells make them particularly well-suited for developing cell-based treatments for osteoporosis, a disease that weakens bones and makes them susceptible to fractures. And thanks to the numerous liposuction procedures performed in the U.S. each year, hASCs are readily available to researchers.

Electron microscope image showing the eroded, inner structure of a back bone in an 89 year old woman with osteoposis. Image courtesy the Bone Research Society

Electron microscope image showing the eroded, inner structure of a back bone in an 89 year old woman with osteoposis. Image courtesy the Bone Research Society.

But a lingering problem with hASCs as a reliable cell source for future therapies is their extreme patient-to-patient variability. Studies have shown that all sorts of factors like gender, body mass index (BMI) and age can have profound effects on the ability of hASCs to multiply and to specialize into bone cells.

Now, University of Missouri researchers describe the novel use of a measuring device to make more quantitative comparisons of different sets of donor hASCs. The instrument, called an electrical cell-substrate impedance spectroscopy (ECIS) – try saying that three times fast! – sends a very weak, noninvasive current through the cells and can measure changes in the cells’ shape in real-time. Other studies had shown that ECIS can quantitatively detect differences between hASCs and human bone marrow-derived mesenchymal stem cells as they mature into their respective cell types.

In the current Stem Cells Translational Medicine study, picked up this week by Health Canal, hASCs were obtained from young (24–36 years old), middle-aged (48–55 years old), and elderly (60–81 years old) donors. The ECIS results showed that stem cells from older donors matured into bone cells much quicker (~ 1day) than the younger cell of cells (~10 day). You might have intuitively thought the youngest stem cells would mature the fastest. But the end result of the difference is that the young set of stem cells multiplied much more than the cells from older donor and they accumulated more calcium over time.

This noninvasive, quantitative tool for predicting a fat stem cell’s potential to specialize into bone has the promise to improve quality control for manufacturing cell therapies, and it also provides researchers a means to better observe the underlying biological basis for this patient-to-patient variability in human fat cells.

Stem cell stories that caught our eye: healing diabetic ulcers, new spinal cord injury insights & an expanding CRISPR toolbox

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.

Stem cells heal diabetic foot ulcers in pilot study
Foot ulcers are one of the many long-term complications that diabetics face. About 15 percent of patients develop these open sores which typically appear at the bottom of the foot. In a quarter of these cases, the ulcers lead to serious infection requiring amputation.


Diabetic foot ulcers are open sores that don’t heal and in many cases leads to amputation. Image source: Izunpharma

But help may be on the horizon in the form of stem cells. Researchers at Mansoura University in Egypt recently presented results of a small study in which 10 patients with diabetic foot ulcers received standard care and another 10 patients received standard care plus injections of mesenchymal stem cells that had been collected from each patient’s own bone marrow. After just six weeks, the stem cell treated group showed a 50% reduction in the foot ulcers while the group with only standard care had a mere 7% reduction.

These superior results with the stem cells were observed even though the group receiving the stem cells had larger foot ulcers to begin with compared to the untreated patients. There are many examples of mesenchymal stem cells’ healing power which make them an extremely popular cell source for hundreds of on-going clinical trials. Mesenchymal stem cells are known to reduce inflammation and increase blood vessel formation, two properties that may be at work to give diabetic foot ulcers the chance to get better.

Medscape Medical News reported on these results which were presented at the 2016 annual meeting of the European Association for the Study of Diabetes (EASD) 2016 Annual Meeting

Suppressing nerve signals to help spinal cord injury victims
Losing the use of one’s limbs is a profound life-altering change for spinal cord injury victims. But their quality of life also suffers tremendously from the loss of bladder control and chronic pain sensations. So much so, victims often say that just improving these secondary symptoms would make a huge improvement in their lives.

While current stem cell-based clinical trials, like the CIRM-funded Asterias study, aim to reverse paralysis by restoring loss nerve signals, recent CIRM-funded animal data published in Cell Stem Cell from UC San Francisco suggest that nerve cells that naturally suppress nerve signals may be helpful for these other symptoms of spinal cord injury.


Mature inhibitory neuron derived from human embryonic stem cells is shown after successfully migrated and integrated into the injured mouse spinal cord.
Photo by Jiadong Chen, UCSF

It turns out that the bladder control loss and chronic pain may be due to overactive nerve signals. So the lab of Arnold Kriegstein transplanted inhibitory nerve cells – derived from human embryonic stem cells – into mice with spinal cord injuries. The scientists observed that these human inhibitory nerve cells, or interneurons, successfully made working connections in the damaged mouse spinal cords. The rewiring introduced by these interneurons also led to reduced pain behaviors in the mice as well as improvements in bladder control.



In a Yahoo Finance interview, Kreigstein told reporters he’s eager to push forward with these intriguing results:


Arnold Kriegstein, UCSF

“As a clinician, I’m very aware of the urgency that’s felt among patients who are often very desperate for treatment. As a result, we’re very interested in accelerating this work toward clinical trials as soon as possible, but there are many steps along the way. We have to demonstrate that this is safe, as well as replicating it in other animals. This involves scaling up the production of these human interneurons in a way that would be compatible with a clinical product.”


Expanding the CRISPR toolbox
If science had a fashion week, the relatively new gene editing technology called CRISPR/Cas9 would be sure to dominate the runway. You can think of CRISPR/Cas9 as a protein and RNA complex that acts as a molecular scissor which directly targets and cuts specific sequences of DNA in the human genome. Scientists are using CRISPR/Cas9 to develop innovative biomedical techniques such as removing disease-causing mutations in stem cells in hopes of developing potential treatments for patients suffering from diseases that have no cures.

What’s particularly interesting about the CRISPR/Cas9 system is that the Cas9 protein responsible for cutting DNA is part of a family of CRISPR associated proteins (Cas) that have similar but slightly different functions. Scientists are currently expanding the CRISPR toolbox by exploring the functions of other CRISPR associated proteins for gene editing applications.

A CIRM-funded team at UC Berkeley is particularly interested in a CRISPR protein called C2c2, which is different from Cas9 in that it targets and cuts RNA rather than DNA. Led by Berkeley professor Jennifer Doudna, the team discovered that the CRISPR/C2c2 complex has not just one, but two, distinct ways that it cuts RNA. Their findings were published this week in the journal Nature.

The first way involves creation: C2c2 helps make the guide RNAs that are used to find the RNA molecules that it wants to cut. The second way involves destruction: after the CRISPR/C2c2 complex finds it’s RNAs of choice, C2c2 can then cut and destroy the RNAs.

Doudna commented on the potential applications for this newly added CRISPR tool in a Berkeley News release:


Jennifer Doudna: Photo courtesy of

“This study expands our molecular understanding of C2c2 to guide RNA processing and provides the first application of this novel RNase. C2c2 is essentially a self-arming sentinel that attacks all RNAs upon detecting its target. This activity can be harnessed as an auto-amplifying detector that may be useful as a low-cost diagnostic.”


Stem cell stories that caught our eye: two studies of the heart and cool stem cell art

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.

Image from Scope Blog.

Image from Scope Blog.

Understanding Heart Defects. Healthy heart tissue is made up of smooth, solid muscle, which is essential for normal heart function. Patients with a heart defect called left ventricular non-compaction (LVNC), lack normal heart tissue in their left ventricle – the largest, strongest blood-pumping chamber – and instead have spongy-looking tissue.

LVNC occurs during early heart development where pieces of heart muscle fail to condense (compact) and instead form an airy, sponge-like network that can leave patients at risk for heart failure and other complications.

A team at Stanford is interested in learning how LVNC occurs in humans, and they’re using human stem cells for the answer. Led by CIRM grantee Joe Wu, the scientists generated induced pluripotent stem cells (iPSCs) from four patients with LVNC. iPSCs are cells that can be turned into any other cell in the body, so Wu turned these cells into iPSC-derived heart muscle in a dish.

Wu’s team was particularly interested in determining why some LVNC patients have symptoms of disease while others seem perfectly normal. After studying the heart muscle cells derived from the four LVNC patients, they identified a genetic mutation in a gene called TBX20. This gene produces a type of protein called a cardiac transcription factor, which controls the expression of other heart related genes.

Upon further exploration, the scientists found that the genetic mutation in TBX20 prevented LVNC heart muscle cells from dividing at their normal rate. If they blocked the signal of mutant TBX20, the heart cells went back to their normal activity and created healthy looking heart tissue.

This study was published in Nature Cell Biology and covered by the Stanford Medicine Scope blog. In an interview with Scope, Joe Wu highlighted the big picture of their work:

Joseph Wu Stanford

Joseph Wu Stanford

“This study shows the feasibility of modeling such developmental defects using human tissue-specific cells, rather than relying on animal cells or animal models. It opens up an exciting new avenue for research into congenital heart disease that could help literally the youngest — in utero — patients.”

Stem Cell Heart Patch. Scientists from the University of Wisconsin, Madison are creating stem cell-based heart patches that they hope one day could be used to treat heart disease.

In a collaboration with Duke and the University of Alabama at Birmingham, they’re developing 3D stem cell-derived patches that contain the three main cell types found in the heart: cardiomyocytes (heart muscle cells), fibroblasts (support cells), and endothelial cells (cells that line the insides of blood vessels). These patches would be transplanted into heart disease patients to replace damaged heart tissue and improve heart function.

As with all research that has the potential for reaching human patients, the scientists must first determine whether the heart patches are safe in animal models. They plan to transplant the heart patches into a pig model – chosen because pigs have similar sized hearts compared to humans.

In a UW-Madison News release, the director of the UW-Madison Stem Cell and Regenerative Medicine Center Timothy Kamp, hinted at the potential for this technology to reach the clinic.

“The excitement here is we’re moving closer to patient applications. We’re at a stage when we need to see how these cells do in a large animal heart attack model. We’ll be making patches of heart muscle that can be applied to these injured areas.”

Kamp and his team still have a lot of work to do to perfect their heart patch technology, but they are thinking ahead. Two issues that they are trying to address are how to prevent a patient’s immune system from rejecting the heart patch transplant, and how to make sure the heart patches beat in sync with the heart they are transplanted into.

Check out the heart patches in action in this video:

(Video courtesy of Xiaojun Lian)

Cool Stem Cell Art! When I was a scientist, I worked with stem cells all the time. I grew them in cell culture dishes, coaxed them to differentiate into brain cells, and used a technique called immunostaining to take really beautiful, colorful pictures of my final cell products. I took probably thousands of pictures over my PhD and postdoc, but sadly, only a handful of these photos ever made it into journal publications. The rest collected dust either on my hard drive or in my lab notebook.

It’s really too bad that at the time I didn’t know about this awesome stem cell art contest called Cells I See run by the Centre for Commercialization of Regenerative Medicine (CCRM) in Ontario Canada and sponsored by the Stem Cell Network.

The contest “is about the beauty of stem cells and biomaterials, seen directly through the microscope or through the interpretive lens of the artist.” Scientists can submit their most prized stem cell images or art, and the winner receives a cash prize and major science-art street cred.

The submission deadline for this year’s contest was earlier this month, and you can check out the contenders on CCRM’s Facebook page. Even better, you can vote for your favorite image or art by liking the photo. The last date to vote is October 15th and the scientist whose image has the most likes will be the People’s Choice winner. CCRM will also crown a Grand Prize winner at the Till & McCulloch Stem Cell Meeting in October.

I’ll leave you with a few of my favorite photos, but please don’t let this bias your vote =)!

"Icy Astrocytes" by Samantha Yammine

“Icy Astrocytes” by Samantha Yammine (Vote here!)

"Reaching for organoids" by Amy Wong

“Reaching for organoids” by Amy Wong (Vote here!)

"Iris" by Sabiha Hacibekiroglu

“Iris” by Sabiha Hacibekiroglu (Vote here!)

Stem cell stories that caught our eye: 3D mini-lungs, Parkinson’s culprit, Motherless babies!

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.

Mimicking human air sacs –  a new lab tool for studying respiratory disease
Studying a flat lawn of cells in a petri dish is so old fashioned these days. The current trend is to use stem cells to create mini-organs called organoids that more closely mimic the actual three dimensional structures that you would find in the human body. We’ve written about the creation of mini-brains, livers, pituitary glands and several other organoids. Now, a UCLA research team has added lung organoids to the list.


3-D bioengineered lung-like tissue (left) resembles adult human lung (right).
Image credit: UCLA Broad Stem Cell Research Center

Reported yesterday in Stem Cells Translational Medicine, the CIRM-funded study describes the technique of nudging lung stem cells, collected from patients’ lung tissue, to self-assemble into 3D structures that resemble air sacs found in the human lung. This technique will surely usher in a better understanding of idiopathic pulmonary fibrosis, a disease that causes scarring of the lungs, leading to shortness of breath and depriving the organs of oxygen. The cause of the disease isn’t known in most cases and, sadly, people usually die within five years of their initial diagnosis.

One of the main challenges in the lab has been reproducing the tale tell scarring seen in this chronic lung disease. When lung cells are taken from pulmonary fibrosis patients and grown as a flat layer, the cells look healthy. But with this novel lung organoid technique, the researchers were able to manipulate the cells to develop the types of scars seen in actual diseased lungs. Better yet, the methodology is very straight-forward, as Dan Wilkinson described in a university press release:

“The technique is very simple. We can make thousands of reproducible pieces of tissue that resemble lung and contain patient-specific cells.”

Now the researchers are in a position to better understand the cellular and molecular basis of the disease and to test out possible treatments that would work best in each individual.

A common thread running through all Parkinson’s cases
The cause of Parkinson’s disease seems straight-forward enough: nerve cells that produce dopamine – a chemical signal that helps generate smooth body movements – progressively die leading to body stiffness, uncontrollable shaking in the limbs and weakened coordination, just to name a few symptoms.

But the underlying genetics of Parkinson’s is anything but simple. Mutations in several genes are associated with family histories of the disease while other mutations in other genes are known to indirectly increase the risk of developing Parkinson’s. These familial forms of Parkinson’s, however, only make up about 15% of all cases; the remaining are so-called sporadic, meaning there’s no obvious family history. So, treating Parkinson’s disease involves treating each of its many forms. But in a CIRM-funded study, published late last week in Cell Stem Cell, Stanford researchers reported on a common thread that appears to run through all forms of Parkinson’s disease.

The team focused on a known mutation in the LRRK2 gene, found in about 1 out of 20 cases of familial Parkinson’s and which pops up in 1 out of 50 cases of sporadic Parkinson’s. The link between LRRK2 and Parkinson’s had not been understood. The Stanford researchers found it plays an important role in the maintenance of mitochondria, structures that produce a cell’s energy needs.


Oh, not that Miro’. We’re talking about the protein Miro!

When mitochondria become damaged or old they begin spewing out molecules that are toxic to the cell. In response, the cell gobbles up these mitochondria but only after the LRRK protein interacts with and removes a protein called Miro which normally anchors the mitochondria to the cell’s internal structures. The mutated form of LRRK2 doesn’t interact with Miro very well and, as a result, Miro holds on to the toxic mitochondria which in turn are not dismantled as rapidly.

You’d think this mechanism of action would to be specific to the LRRK2-mutant Parkinson’s but to the scientists’ pleasant surprise, it wasn’t. They discovered this result by creating induced pluripotent stem cells from skin samples collected from twenty different subjects:  four healthy subjects; five with the sporadic Parkinson’s; six with familial Parkinson’s from LRRK2 mutations and five with familial patients from other mutations. The iPS cells were grown into dopamine-producing nerve cells, the kind that die off in Parkinson’s disease. With these cells in hand, they observed the impact of intentionally damaging the mitochondria.

As expected, this damage to the nerve cells from the healthy subjects led to the breakdown of Miro which in turn allowed the detachment and degradation of mitochondria. Also as expected, the nerve cells from patients with the LRRK2 mutant showed delays in the release and degradation of mitochondria. But when the team looked at the other Parkinson’s nerve cells not associated with the LRRK2 mutant, they found the same delay in the release of Miro and degradation of mitochondria.

This result points to Miro as a common player in all forms of Parkinson’s. Xinnan Wang, the team’s leader, spoke about the exciting implications of these findings in a university press release:


Xinnan Wang

“Existing drugs for Parkinson’s largely work by supplying precursors that faltering dopaminergic nerve cells can easily convert to dopamine. But that doesn’t prevent those cells from dying, and once they’ve died you can’t bring them back. Measuring Miro levels in skin fibroblasts from people at risk of Parkinson’s might someday prove beneficial in getting an accurate, early diagnosis. And medicines that lower Miro levels could prove beneficial in treating the disease.” 

A cautionary tale about science communication
What to leave in, what to leave out: it’s the continual dilemma (I must add a fun dilemma) for a science writer. When writing for a general audience, if you describe a research report in too much detail you’re likely to quickly lose your reader. But not adding enough detail can lead the reader to draw conclusions that aren’t accurate. And just a like a game of telephone, as the story is passed along from one source to another, the resulting storyline has little resemblance to the original research.

Research published this week in Nature Communications provides a case in point. Many of news outlets that picked up the research story which involved the successful production of mouse pups from mixing sperm with an novel type of egg cell that had been induced to divide before fertilization. The resulting headlines suggested that scientists had identified an end run around the need for a female’s egg to produce offspring. Based on a quick glance at these condensed summaries of the research report, you’d think motherless babies were just around the corner.

Gretchen Vogel at Science Magazine wrote a terrific autopsy of this news story, describing in five steps how it took on a life of its own. It’s a humorous (I personally LOL’d when I read it) yet serious cautionary tale of how science communication can go awry. I highly recommended the short piece. For a sneak peek, here’s her “five easy steps to create a tabloid science headline”:

  1. vogel_

    Gretchen Vogel

    Take one jargon-filled paper title: “Mice produced by mitotic reprogramming of sperm injected into haploid parthenogenotes

  2. Distill its research into more accessible language. Text of Nature Communications press release: Mouse sperm injected into a modified, inactive embryo can generate healthy offspring, shows a paper in Nature CommunicationsAnd add a lively headline: “Mouse sperm generate viable offspring without fertilization in an egg
  3. Enlist an organization to invite London writers to a press briefing with paper’s authors.
    Headline of Science Media Centre press release: “Making embryos from a non-egg cell
  4. Have same group distribute a laudatory quote from well-known and respected scientist: 
    “[It’s] a technical tour de force.”
  5. Bake for 24 hours and present without additional reporting. Headline in The Telegraph: “Motherless babies possible as scientists create live offspring without need for female egg,” and in The Guardian: “Skin cells might be used instead of eggs to make embryos, scientists say.”


Stem cell stories that caught our eye: improving heart care, fixing sickle cell disease, stem cells & sugar

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.

Using “disease in a dish” model to improve heart care
Medications we take to improve our quality of life might actually be putting our lives in danger. For example, some studies have shown that high doses of pain killers like ibuprofen can increase our risk of heart problems or stroke. Now a new study has found a way of using a person’s own cells, to make sure the drugs they are given help, and don’t hinder their recovery.


Cardiac muscle cells from boy with inherited heart arrhythmia.
Image: Emory University

Researchers at Emory University in Atlanta took skin cells from a teenage boy with an inherited heart arrhythmia, and turned them into induced pluripotent stem (iPS) cells – a kind of cell that can then be turned into any other cell in the body. They then turned the iPS cells into heart muscle cells and used those cells to test different medications to see which were most effective at treating the arrhythmia, without causing any toxic or dangerous side effects.

The study was published in Disease Models & Mechanisms. In a news release co-author Peter Fischbach, said the work enables them to study the impact on a heart cell, without taking any heart cells from patients:

“We were able to recapitulate in a petri dish what we had seen in the patient. The hope is that in the future, we will be able to do that in reverse order.”

Switching a gene “off” to ease sickle cell disease pain:
Sickle cell disease (SCD) is a nasty, inherited condition that not only leaves people in debilitating pain, but also shortens their lives. Now researchers at Dana-Farber and Boston Children’s Cancer and Blood Disorders Center have found a way that could help ease that pain in some patients.

SCD is caused by a mutation in hemoglobin, which helps carry oxygen around in our blood. The mutation causes normally soft, round blood cells to become stiff and sickle-shaped. These often stick together, blocking blood flow, causing intense pain, organ damage and even strokes.

In this study, published in the Journal of Clinical Investigation, researchers took advantage of the fact that SCD is milder in people whose red blood cells have a fetal form of hemoglobin, something which for most of us tails off after we are born. They found that by “switching off” a gene called BCL11A they could restart that fetal form of hemoglobin.

They did this in mice successfully. Senior author David Williams, in a story picked up by Health Medicine Network, says they now hope to try this in people:

“BCL11A represses fetal hemoglobin, which does not lead to sickling, and also activates beta hemoglobin, which is affected by the sickle-cell mutation. So when you knock BCL11A down, you simultaneously increase fetal hemoglobin and repress sickling hemoglobin, which is why we think this is the best approach to gene therapy in sickle cell disease.”

CIRM already has a similar approach in clinical trials. UCLA’s Don Kohn is using a genetic editing technique to add a novel therapeutic hemoglobin gene that blocks sickling of the red blood cells and hopefully cure the patient altogether. This fun video gives a quick summary of the clinical trial:

How a stem cell’s sugar metabolism controls its transformation potential
While CIRM makes its push to fund 50 more stem cell-based clinical trials by 2020, we also continue to fund research that helps us better understand stem cells. Case in point, this week a UCLA research team funded in part by CIRM reported that an embryonic stem cell’s sugar metabolism changes as its develops and that this difference has big implications on cell fate.



The study, published in Cell Stem Cell, compared so-called “naïve” and “primed” human embryonic stem cells (ESCs). The naïve cells represent a very early stage of embryo development and the primed cells represent a slightly later stage. All cells use the sugar, glucose, to provide energy, though the researchers discovered that the naive stem cells “ate up” glucose four times faster than the primed stem cells (A fascinating side note is they also found the exact opposite behavior in mice: naïve mouse ESCs metabolize glucose slower than primed mouse ESCs. This is a nice example of why it’s important to study human cells to understand human biology). It turns out this difference effects each cells ability to differentiate, or specialize, into a mature cell type. When the researchers added a drug that inhibits glucose metabolism to the naïve cells and stimulated them down a brain cell fate, three times more of the cells specialized into nerve cells.

Their next steps are to understand exactly how the change in glucose metabolism affects differentiation. As Heather Christofk mentioned in a university press release, these findings could ultimately help researchers who are manipulating stem cells to develop cell therapy products:

“Our study proves that if you carefully alter the sugar metabolism of pluripotent stem cells, you can affect their fate. This could be very useful for regenerative medicine.”

Stem cell stories that caught our eye: functioning liver tissue, making new bone, stem cells and mental health

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.

Functioning liver tissue. Scientists are looking to stem cells as a potential alternative treatment to liver transplantation for patients with end-stage liver disease. Efforts are still in their early stages but a study published this week in Stem Cells Translational Medicine, shows how a CIRM-funded team at the Children’s Hospital Los Angeles (CHLA) successfully generated partially functional liver tissue from mouse and human stem cells.

Biodegradable scaffold (left) and human tissue-engineered liver (right) (Photo courtesy of The Saban Research Institute at Children’s Hospital Los Angeles)

Biodegradable scaffold (left) and human tissue-engineered liver (right) (Photo courtesy of The Saban Research Institute at Children’s Hospital Los Angeles)

The lab had previously developed a protocol to make intestinal organoids from mouse and human stem cells. They were able to tweak the protocol to generate what they called liver organoid units and transplanted the tissue-engineered livers into mice. The transplants developed cells and structures found in normal healthy livers, but their organization was different – something that the authors said they would address in future experiments.

Impressively, when the tissue-engineered liver was transplanted into mice with liver failure, the transplants had some liver function and the liver cells in these transplants were able to grow and regenerate like in normal livers.

In a USC press release, Dr. Kasper Wang from CHLA and the Keck school of medicine at USC commented:

“A cellular therapy for liver disease would be a game-changer for many patients, particularly children with metabolic disorders. By demonstrating the ability to generate hepatocytes comparable to those in native liver, and to show that these cells are functional and proliferative, we’ve moved one step closer to that goal.”


Making new bone. Next up is a story about making new bone from stem cells. A group at UC San Diego published a study this week in the journal Science Advances detailing a new way to make bone forming cells called osteoblasts from human pluripotent stem cells.

Stem cell-derived osteoblasts (bone cells). Image credit Varghese lab/UCSD.

Stem cell-derived osteoblasts (bone cells). Image credit Varghese lab/UCSD.

One way that scientists can turn pluripotent stem cells into mature cells like bone is to culture the stem cells in a growth medium supplemented with small molecules that can influence the fate of the stem cells. The group discovered that by adding a single molecule called adenosine to the growth medium, the stem cells turned into osteoblasts that developed vascularized bone tissue.

When they transplanted the stem cell-derived osteoblasts into mice with bone defects, the transplanted cells developed new bone tissue and importantly didn’t develop tumors.

 In a UC newsroom release, senior author on the study and UC San Diego Bioengineering Professor Shyni Varghese concluded:

“It’s amazing that a single molecule can direct stem cell fate. We don’t need to use a cocktail of small molecules, growth factors or other supplements to create a population of bone cells from human pluripotent stem cells like induced pluripotent stem cells.”


Stem cells and mental health. Brad Fikes from the San Diego Union Tribune wrote a great article on a new academic-industry partnership whose goal is to use human stem cells to find new drugs for mental disorders. The project is funded by a $15.4 million grant from the National Institute of Mental Health.

Academic scientists, including Rusty Gage from the Salk Institute and Hongjun Song from Johns Hopkins University, are collaborating with pharmaceutical company Janssen and Cellular Dynamics International to develop induced pluripotent stem cells (iPSCs) from patients with mental disorders like bipolar disorder and schizophrenia. The scientists will generate brain cells from the iPSCs and then work with the companies to test for potential drugs that could be used to treat these disorders.

In the article, Fred Gage explained that the goal of this project will be used to help patients rather than generate data points:

Rusty Gage, Salk Institute.

Rusty Gage, Salk Institute.

“Gage said the stem cell project is focused on getting results that make a difference to patients, not simply piling up research information. Being able to replicate results is critical; Gage said. Recent studies have found that many research findings of potential therapies don’t hold up in clinical testing. This is not only frustrating to patients, but failed clinical trials are expensive, and must be paid for with successful drugs.”

“The future of this will require more patients, replication between labs, and standardization of the procedures used.”

Stem cell stories that caught our eye: Salamander limb regrowth, mass producing cells for kidneys and halting cancer stem cells

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.

Fun with axolotls.  Axolotls, the albino aquatic critters that look like they have feathers growing out of the backs of their heads, have long been a favorite model for studying how they and their salamander cousins regrow limbs. But only recently, with refined methods for turning specific genes on and off, have we begun to really understand this amazing feat.


Carl Zimmer, national correspondent for the online publication STAT, interviewed Jessica Whited of Harvard-affiliated Brigham and Women’s Hospital about her work trying to understand the genetics of limb regrowth and posted both a four-minute video and a short story about the research. Part of the video series Zimmer calls “Science Happens,” the interview lets Whited explain that when a limb is cut off, the animal summons cells called blastemas to the stump. Those cells have properties like stem cells in that they can make different tissues like the bone, skin and muscle needed to grow a limb, but they seem to do this by selectively turning genes on and off.

With a mix of cartoon drawings and real lab images, the video provides an easy to follow explanation of how the researchers turn off individual genes and then look for the effect. And I have to say I agree with Zimmer when talking about the axolotls he declares “I think they’re creepy.”


Advance for kidney disease.  Often in stem cell research you don’t want the starting stem cell and you don’t want the end desired tissue, you want the middleman called a progenitor that has already decided it wants to become the end tissue, but can still mass produce itself. Instead of being handed a roll of 10 dollar bills, you have a printing press with Hamilton’s face already set on the printing plate.

kidney progenitors Salk

Progenitor cells (bright red) growing in a kidney

In CIRM-funded research published this week in Cell Stem Cell a team at the Salk Institute has found a way to configure that printing press for nephron progenitor cells, the cells that yield the vital nephrons that allow your kidneys to cleanse your blood. While many have tried to mass produce these vital cells to repair damaged kidneys, they have not had much luck. These cells do not like to stay in the progenitor state. Once they are on the path toward the end tissue they like to keep on moving in that direction.

The Salk team, led by Juan Carlos Izpisua Belmonte, got around this by changing the progenitor cells’ environment. Instead of a flat lab dish, they grew them in 3D cultures and gave them a new mix of signaling molecules.

“We provide a proof-of-principle for how to make and maintain unlimited numbers of precursor kidney cells,” said Izpisua Belmonte in an institute press release posted by HealthMedicineNet. “Having a supply of these cells could be a starting point to grow functional organs in the laboratory as well as a way to begin applying cell therapy to kidneys with malfunctioning genes.”

Their system worked first in mouse cells and then in human cells. They predicted that the methods could be used to grow progenitor cells for many other tissues.


Halting cancer stem cells. The bad guys of the stem cell world, cancer stem cells (CSCs), are turning out to have a number of vulnerabilities, and many companies around the world have staked their fortunes on attacking one of those weak spots. While we have known for some time that CSCs require proteins in the Wnt family to grow, we haven’t had a good way of blocking that path. Now researchers at the Riken Center and National Cancer Center in Japan claim they have a candidate drug, at least for colon cancer.

They screened a library of compounds likely to inhibit the Wnt pathway and tested them in mice that had received transplants of human colon cancer. They found one, NCB-0846 that can be administered orally, that was able to suppress the cancer grafts.

 “We’re very encouraged by our promising preclinical data for NCB-0846, especially considering the difficulty in targeting this pathway to date, and shortly we hope to conduct a clinical trial at the NCC hospitals” said Dr. Tesshi Yamada of the National Cancer Center in a Riken release posted by ScienceCodex.

CIRM funds several team trying to halt CSCs, each team targeting a different vulnerability on the CSCs, including teams at Stanford, and at University of California campuses in San Diego and Los Angeles.

Stem cell stories that caught our eye: Zika virus and adult brains, a step toward precision medicine and source of blood stem cells

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.

Zika virus and the adult brain.  While almost all the press attention for the Zika virus has centered on pregnant women and the devastating impact the virus can have on their developing babies, a few stories have noted that while most adults don’t know they have been infected, a few do. The one significant impact seen is a relatively rare incidence of Guillain-Barre Syndrome, which can cause temporary partial paralysis. That has triggered a few researchers to look for other impacts in adults infected with the mosquito-borne virus.


Researchers trying to understand why the virus leads to the underdeveloped brains known as microcephaly, in infants have shown the virus does its nasty work at the level of the nerve stem cell. Although adults have far fewer nerve stem cells than a developing fetus, they do have some. So a team at Rockefeller University in New York and the La Jolla Institute for Allergy and Immunology decided to look for any effects of infection on adult nerve stem cells in mice.  They published the work this week in the journal Cell Stem Cell and report a dramatic reduction in adult nerve stem cells in infected mice.

“Adult neurogenesis is implicated in learning and memory,” said the La Jolla Institute’s Sujan Shresta in a press release from the journal. “We don’t know what this would mean in terms of human diseases, or if cognitive behaviors of an individual could be impacted after infection.”

Mice are normally resistant to Zika infection, so the researchers first had to genetically engineer mice to be susceptible to infection. That means several layer of caveats and more research are needed before any assertions about adult impact of Zika infection in humans.

This work captured considerable press attention including in Buzzfeed, NBC and USNews and World Report.


Heart felt precision medicine.  With the boost of a special initiative launched by the Obama administration, precision medicine is becoming all the rage, at least as a goal. While a few cancer therapies currently use this concept of matching therapies to a specific patient’s genetic makeup, few doctors outside of oncology can turn to similarly precise therapies.

Cardio cells image

Heart muscle cells

Work from a CIRM-funded team at Stanford has moved other doctors a bit closer to this goal for heart disease. But this research will not lead to treating it, rather it could allow doctors to prevent therapies used for other diseases from causing heart disease. Joseph Wu and his team have made two discoveries that help validate the use of the iPS reprogramming technique to make patient-specific stem cells and then mature them into heart muscle cells and see how those cells react to specific drugs.

“Thirty percent of drugs in clinical trials are eventually withdrawn due to safety concerns, which often involve adverse cardiac effects,” said Wu in a press release picked up by ScienceNewsLine. “This study shows that these cells serve as a functional readout to predict how a patient’s heart might respond to particular drug treatments and identify those who should avoid certain treatments.”



Joseph Wu

There has always been some concern that the genetic manipulation used to create iPS cells changes the genetics of any adult tissue you make from the cells. So, with samples from three patients who were undergoing heart biopsy or transplant, which allowed harvesting mature heart muscle, the team compared the genetic signature of the adult heart muscle and that of heart muscle created from iPS cells.  They found no significant differences.

With skin samples from another seven subjects they created iPS cells and then heart muscle and compared their genetic signatures. The found some slight difference in all seven, but dramatic differences in one. That difference was in a genetic pathway involved in the inner workings of heart muscle. When they treated those cells with a diabetes drug that had been linked to heart problems, the cells reacted quite differently from the cells of the other six subjects treated with the same drug. With this knowledge a doctor could avoid ever choosing to put that particular patient on that diabetes drug.


Source of blood stem cells matters.  For years, bone marrow transplant—the one currently routine stem cell therapy—required digging into someone bone to harvest the stem cells. Over the decades that the procedure has been saving thousands of lives doctors have found less invasive methods to get the stem cells using drugs to “mobilize” the marrow stem cells and get them to move into the blood stream where they can be harvested.

While stem cell donors often find the new procedure a vast improvement, no one had done a thorough review of the outcomes for patients who receive stem cells gathered by the different procedures until a paper this week from the Fred Hutchison Cancer Research Center in Seattle. While they did not find any differences in overall life expectancy, they found vastly different outcomes in quality of life including psychological wellbeing and ability to return to work.

The Hutchison team attributed most of this difference to a lower rate of Graft Versus Host Disease (GVHD), possibly the most dangerous side effect of the procedure, which occurs when the stem cell transplant also contains adult immune system cells from the donor and those “graft” cells attack the “host,” the patient. It makes sense that when you harvest cells from the blood stream you would be more likely to also capture mature immune cells than when you harvest cells from marrow. And GVHD can be extremely painful, debilitating, and often deadly.

Stephanie Lee Hutchison

Stephanie Lee

“When both your disease and the recommended treatment are life-threatening, I don’t think people are necessarily asking ‘which treatment is going to give me better quality of life years from now?'” said Stephanie Lee the lead author in a press release from the cancer center. “Yet, if you’re going to make it through, as many patients do, you want to do it with good quality of life. That’s the whole point of having the transplant.”

Stem cell stories that caught our eye: better bone marrow transplants, turbo charging anti-inflammatory stem cells and Zika’s weapons

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.

Three steps to better BMT.  Bone marrow stem cell transplants (BMT) save the lives of many thousands of patients every year, but they also kill a significant number of the blood stem cell transplantcancer and immune disorder patients the procedure is intended to save. In order to make room in the bone marrow for new blood-forming stem cells, you first have to get rid of most of the stem cells already there, and the radiation and chemotherapy to do this proves too toxic for some patients. Also, donor marrow can contain immune cells from the donor that can attack the recipient causing Graft Versus Host Disease (GVHD), which can also be fatal.

Add this all together and physicians tend to save BMT for the patients with the most life threatening forms of the diseases.  A CIRM-funded team at Stanford has developed a three-step process that seems to dramatically reduce all those risks potentially opening up the procedure to less-sick patients including patients with life-altering, but not life-threatening, autoimmune diseases such as lupus and less severe forms of multiple sclerosis.

Experimenting in mice, they first used an antibody that attaches to a marker on blood stem cells called c-kit. But by itself that antibody could not get rid of enough of the stem cells. So, they added a second agent that blocked another protein, CD47, on the surface of blood stem cells. With that protein blocked, the animals own immune cells called macrophages, could destroy the blood stem cells. Then to make the donor cells safer, they used a technology they had developed many years ago to remove any straggler immune cells from the donor stem cells, thus drastically eliminating the chances for GVHD.

judith shizuru


“If it works in humans like it did in mice, we would expect that the risk of death from blood stem cell transplant would drop from 20 percent to effectively zero,” said senior author Judith Shizuru in a university press release posted by HealthCanal.

She went on to compare blood stem cell transplants to planting a new field of crops saying they were looking for a better way to first clear the field for planting and then a better way to do the planting. CIRM funded the team to develop the method for use with Severe Combined Immune Deficiency (SCID). The team published the current mouse study in the journal Science Translational Medicine.


Building a better anti-inflammatory stem cell.  Of the more than 700 stem cell therapy clinical trials underway around the world, more than half use the type of stem cell called a mesenchymal stem cell (MSC) found in bone marrow and fat—in marrow it resides alongside the blood-forming stem cells. Some of those trials are tapping into MSC’s ability to build bone, cartilage and blood vessels, but many are counting on their strong anti-inflammatory properties to fight autoimmune diseases.

When MSCs find themselves in an environment with pro-inflammatory proteins they respond by producing anti-inflammatory proteins. To enhance that effect some teams have bathed their MSC’s in pro-inflammatory proteins before injecting them into patients, but the effect of those proteins wears off quickly. So, a team led by CIRM-funded researcher Todd McDevitt at the Gladstone Institutes in San Francisco has bioengineered a way to make the effect long term.


Gladstone used a CIRM Research Leadership award to recruit McDevitt from Georgia Tech

They loaded the pro-inflammatory proteins onto sugar-based particles that they imbedded in the middle of clusters of MSCs. The bioengineered complex slowly releases the cues to the MSCs and they in turn produced the desired anti-inflammatory proteins in greater quantities and much longer than in any other experiment.

 “A patient taking anti-inflammatory medication may not have high enough levels of inflammation to trigger the cells. We engineered the MSCs to ensure that they are consistently activated, so they can reliably dampen the immune response for longer,” said McDevitt in an institute press release.

The team published their research in Stem Cells Translational Medicine.


Stem cells used to identify Zika’s weapon.  It has been difficult for researchers to think about how to stop the Zika virus’ havoc on fetal brains without knowing how the virus does

Zika Virus

its evil deed. Now, a team at the University of Southern California (USC) has used fetal stem cells to discover two proteins that seem to be Zika’s key weapons.

Viruses often hijack our normal cell processes to enhance their ability to multiply and at the same time do harm to the host. In this case, the two proteins named NS4A and NS4B play key roles in the cell path for normal cell growth and disposal of damaged cells. When exploited by the virus, the two proteins result in cells being destroyed and not replaced.

“Those two viral proteins are ultimately the target for therapy development,” said USC’s Jae Jung in an article posted by Kaiser Health News.

As is typical with this news source, the author goes on to provide considerable high quality background about the Zika outbreak and efforts to find a vaccine or therapy, in this case quoting experts from Texas Children’s Hospital and Baylor.


Cloning fact timeline.  With the 20th anniversary last month of the birth of Dolly the sheep, the first cloned mammal, cloning seems to be much in discussion these days. So for


science nerds who like to keep back up facts handy CNN published a timeline of key events starting with the 1952 Nobel-winning discovery that you could replace the nucleus of a frog’s egg with the nucleus from another cell and still get the egg to develop into a tadpole. And 22 events later, it ends in 2014 with the first use of using cloning techniques to create stem cells that matched an adult.