Stem Cell Roundup: The brain & obesity; iPSCs & sex chromosomes; modeling mental illness

Stem Cell Image of the Week:
Obesity-in-a-dish reveals mutations and abnormal function in nerve cells

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Image shows two types of hypothalamic neurons (in magenta and cyan) that were derived from human induced pluripotent stem cells.
Credit: Cedars-Sinai Board of Governors Regenerative Medicine Institute

Our stem cell image of the week looks like the work of a pre-historic cave dweller who got their hands on some DayGlo paint. But, in fact, it’s a fluorescence microscopy image of stem cell-derived brain cells from the lab of Dhruv Sareen, PhD, at Cedars-Sinai Medical Center. Sareen’s team is investigating the role of the brain in obesity. Since the brain is a not readily accessible organ, the team reprogrammed skin and blood cell samples from severely obese and normal weight individuals into induced pluripotent stem cells (iPSCs). These iPSCs were then matured into nerve cells found in the hypothalamus, an area of the brain that regulates hunger and other functions.

A comparative analysis showed that the nerve cells derived from the obese individuals had several genetic mutations and had an abnormal response to hormones that play a role in telling our brains that we are hungry or full. The Cedars-Sinai team is excited to use this obesity-in-a-dish system to further explore the underlying cellular changes that lead to excessive weight gain. Ultimately, these studies may reveal ways to combat the ever-growing obesity epidemic, as Dr. Sareen states in a press release:

“We are paving the way for personalized medicine, in which drugs could be customized for obese patients with different genetic backgrounds and disease statuses.”

The study was published in Cell Stem Cell

Differences found in stem cells derived from male vs female.

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Microscope picture of a colony of iPS cells. Credit: Vincent Pasque

Scientists at UCLA and KU Leuven University in Belgium carried out a study to better understand the molecular mechanisms that control the process of reprogramming adult cells back into the embryonic stem cell-like state of induced pluripotent stem cells (iPSCs). Previous studies have shown that female vs male embryonic stem cells have different patterns of gene regulation. So, in the current study, male and female cells were analyzed side-by-side during the reprogramming process.  First author Victor Pasquale explained in a press release that the underlying differences stemmed from the sex chromosomes:

In a normal situation, one of the two X chromosomes in female cells is inactive. But when these cells are reprogrammed into iPS cells, the inactive X becomes active. So, the female iPS cells now have two active X chromosomes, while males have only one. Our results show that studying male and female cells separately is key to a better understanding of how iPS cells are made. And we really need to understand the process if we want to create better disease models and to help the millions of patients waiting for more effective treatments.”

The CIRM-funded study was published in Stem Cell Reports.

Using mini-brains and CRISPR to study genetic linkage of schizophrenia, depression and bipolar disorder.

If you haven’t already picked up on a common thread in this week’s stories, this last entry should make it apparent: iPSC cells are the go-to method to gain insight in the underlying mechanisms of a wide range of biology topics. In this case, researchers at Brigham and Women’s Hospital at Harvard Medical School were interested in understanding how mutations in a gene called DISC1 were linked to several mental illnesses including schizophrenia, bipolar disorder and severe depression. While much has been gleaned from animal models, there’s limited knowledge of how DISC1 affects the development of the human brain.

The team used human iPSCs to grow cerebral organoids, also called mini-brains, which are three-dimensional balls of cells that mimic particular parts of the brain’s anatomy. Using CRISPR-Cas9 gene-editing technology – another very popular research tool – the team introduced DISC1 mutations found in families suffering from these mental disorders.

Compared to cells with normal copies of the DISC1 gene, the mutant organoids showed abnormal structure and excessive cell signaling. When an inhibitor of that cell signaling was added to the growing mutant organoids, the irregular structures did not develop.

These studies using human cells provide an important system for gaining a better understanding of, and potentially treating, mental illnesses that victimize generations of families.

The study was published in Translation Psychiatry and picked up by Eureka Alert.

Stem Cell Roundup: watching brain cells in real time, building better heart cells, and the plot thickens on the adult neurogenesis debate

Here are the stem cell stories that caught our eye this week.

Watching brain cells in real time

This illustration depicts a new method that enables scientists to see an astrocyte (green) physically interacting with a neuronal synapse (red) in real time, and producing an optical signal (yellow). (Khakh Lab, UCLA Health)

Our stem cell photo of the week is brought to you by the Khakh lab at UCLA Health. The lab developed a new method that allows scientists to watch brain cells interact in real time. Using a technique called fluorescence resonance energy-transfer (FRET) microscopy, the team can visualize how astrocytes (key support cells in our central nervous system) and brain cells called neurons form connections in the mouse brain and how these connections are affected by diseases like Alzheimer’s and ALS.

Baljit Khakh, the study’s first author, explained the importance of their findings in a news release:

“This new tool makes possible experiments that we have been wanting to perform for many years. For example, we can now observe how brain damage alters the way that astrocytes interact with neurons and develop strategies to address these changes.”

The study was published this week in the journal Neuron.


Turn up the power: How to build a better heart cell (Todd Dubnicoff)

For years now, researchers have had the know-how to reprogram a donor’s skin cells into induced pluripotent stem cells (iPSCs) and then specialize them into heart muscle cells called cardiomyocytes. The intervening years have focused on optimizing this method to accurately model the biology of the adult human heart as a means to test drug toxicity and ultimately develop therapies for heart disease. Reporting this week in Nature, scientists at Columbia University report an important step toward those goals.

The muscle contractions of a beating heart occur through natural electrical impulses generated by pacemaker cells. In the case of lab-grown cardiomyocytes, introducing mechanical and electrical stimulation is required to reliably generate these cells. In the current study, the research team showed that the timing and amount of stimulation is a critical aspect to the procedure.

The iPS-derived cardiomyocytes have formed heart tissue that closely mimics human heart functionality at over four weeks of maturation. Credit: Gordana Vunjak-Novakovic/Columbia University.

The team tested three scenarios on iPSC-derived cardiomyocytes (iPSC-CMs): no electrical stimulation for 3 weeks, constant stimulation for 3 weeks, and finally, two weeks of increasingly higher stimulation followed by a week of constant stimulation. This third setup mimics the changes that occur in a baby’s heart just before and just after birth.

These scenarios were tested in 12 day-old and 28 day-old iPSC-CMs. The results show that only the 12 day-old cells subjected to the increasing amounts of stimulation gave rise to fully mature heart muscle cells. On top of that, it only took four weeks to make those cells. Seila Selimovic, Ph.D., an expert at the National Institutes of Health who was not involved in the study, explained the importance of these findings in a press release:

“The resulting engineered tissue is truly unprecedented in its similarity to functioning human tissue. The ability to develop mature cardiac tissue in such a short time is an important step in moving us closer to having reliable human tissue models for drug testing.”

Read more at: https://phys.org/news/2018-04-early-bioengineered-human-heart-cells.html#jCp


Yes we do, no we don’t. More confusion over growing new brain cells as we grow older (Kevin McCormack)

First we didn’t, then we did, then we didn’t again, now we do again. Or maybe we do again.

The debate over whether we are able to continue making new neurons as we get older took another twist this week. Scientists at Columbia University said their research shows we do make new neurons in our brain, even as we age.

This image shows what scientists say is a new neuron in the brain of an older human. A new study suggests that humans continue to make new neurons throughout their lives. (Columbia University Irving Medical Center)

In the study, published in the journal Cell Stem Cell, the researchers examined the brains of 28 deceased donors aged 14 to 79. They found similar numbers of precursor and immature neurons in all the brains, suggesting we continue to develop new brain cells as we age.

This contrasts with a UCSF study published just last month which came to the opposite conclusion, that there was no evidence we make new brain cells as we age.

In an interview in the LA Times, Dr. Maura Boldrini, the lead author on the new study, says they looked at a whole section of the brain rather than the thin tissues slices the UCSF team used:

“In science, the absence of evidence is not evidence of absence. If you can’t find something it doesn’t mean that it is not there 100%.”

Well, that resolves that debate. At least until the next study.

Stem Cell Roundup: Crafty Cancer, Fighting Viruses, and Brainstorm ALS Trial Expands to Canada

TGIF! Here is your weekly dose of stem cell news…

Shapeshifting cancer cells

This week’s awesome stem cell photo comes with a bizarre story and bonus video footage.

New research from Duke has found that some lung cancer cells with errors in transcription factors begin to resemble their nearest relatives – the cells of the stomach and gut. (Credit – Tata Lab, Duke University)

Researchers at Duke University were studying lung tumor samples and discovered something that didn’t quite belong. Inside the lung tumors were miniature parts of the digestive system including the stomach, duodenum and small intestine. It turns out that the lung cancer cells (and cancer cells in general) are super crafty and had turned off the expression of a gene called NKX2-1. This gene is a master switch that tells developing cells to turn into lung cells. Without this command, cells switch their identity and mature into gut tissue instead. By manipulating these master switches, cancer cells are able to develop resistance to chemotherapy and other cancer treatments.

So, what does this bizarre finding mean for cancer research? Purushothama Rao Tata, first author on the Developmental Cell study, provided an answer in a news release:

“Cancer biologists have long suspected that cancer cells could shape shift in order to evade chemotherapy and acquire resistance, but they didn’t know the mechanisms behind such plasticity. Now that we know what we are dealing with in these tumors – we can think ahead to the possible paths these cells might take and design therapies to block them.”

For more cool photos and insights into this study, watch the Duke Univeristy video below.


Secrets to the viral-fighting ability of stem cells uncovered (Todd Dubnicoff)

I’ve been writing about stem cells for many years and thought I knew most of the basic info about these amazing cells. But up until this week, I had no idea that stem cells are known to fight off viral infections much better than other cells. It does makes sense though. Stem cells give rise to and help maintain all the organs and tissues of the body. So, it would be bad news if, let’s say, a muscle stem cell multiplied to repair damaged tissue while carrying a dangerous virus.

How exactly stem cells fend off attacking viruses is a question that has eluded researchers for decades. But this week, results published in Cell by Rockefeller University scientists may provide an answer.

Stem cells lacking their protective genes are susceptible to infection by the dengue virus, in red. (Rockefeller University)

The researchers found that liver cells and stem cells defend themselves against viruses differently. In the presence of a virus, liver cells and most other cells react by releasing large amounts of interferon, a protein that acts as a distress signal to other cells in the vicinity. That signal activates hundreds of genes responsible for attracting protective immune cells to the site of infection.

Stem cells, however, are always in this state of emergency. Even in the absence of interferon, the antiviral genes were activated in stem cells. And when the stem cells were genetically engineering to lack some of the antiviral genes, the cells no longer could stop viral infection.

In a press release, senior author Charles Rice explained the importance of this work:

“By understanding more about this biology in stem cells, we may learn more about antiviral mechanisms in general.”


CIRM-funded clinical trial for ALS now available next door – in Canada (Kevin McCormack)

In kindergarten we are taught that it’s good to share. So, we are delighted that a Phase 3 clinical trial for ALS – also known as Lou Gehrig’s disease – that CIRM is helping fund is now expanding its reach across the border from the U.S. into Canada.

Brainstorm Cell Therapeutics, the company behind the therapy, says it is going to open a clinical trial site in Canada because so many Canadians have asked for it.

The therapy, as we described in a recent blog post, takes mesenchymal stem cells from the patient’s own bone marrow. Those cells are then modified in the lab to be able to churn out specific proteins that can help protect the brain cells attacked by ALS. The cells are then transplanted back into the patient and the hope is they will slow down, maybe even stop the progression of the disease.

Earlier studies showed the therapy was safe and seemed to benefit some patients. Now people with ALS across our northern border will get a chance to see if it really works.

Chaim Lebovits, the president and chief executive officer of BrainStorm, said in a press release:

“Although there are thousands of patients worldwide with ALS, we initially designed the Phase 3 trial to enroll U.S.-based patients only, primarily to make it easier for patient follow-up visits at the six U.S. clinical sites. However, due to an outpouring of inquiry and support from Canadian patients wanting to enroll in the trial, we filed an amendment with the FDA [the U.S. Food and Drug Administration] to allow Canada-based ALS patients to participate.”

We are happy to share.

Stem Cell Roundup: hESCs turn 20, tracking cancer stem cells, new ALS gene ID’d

Stem Cell Image of the Week

Picture1This week’s stunning stem cell image is brought to you by researchers in the Brivanlou Lab at Rockefeller University. What looks like the center of a sunflower is actual a ball of neural rosettes derived from human embryonic stem cells (ESCs). Neural rosettes are structures that contain neural stem and progenitor cells that can further specialize into mature brain cells like the stringy, blue-colored neurons in this photo.

This photo was part of a Nature News Feature highlighting how 20 years ago, human ESCs sparked a revolution in research that’s led to the development of ESC-based therapies that are now entering the clinic. It’s a great read, especially for those of you who aren’t familiar with the history of ESC research.

Increase in cancer stem cells tracked during one patient’s treatment
Cancer stem cells are nasty little things. They have the ability to evade surgery, chemotherapy and radiation and cause a cancer to return and spread through the body. Now a new study says they are also clever little things, learning how to mutate and evolve to be even better at evading treatment.

Researchers at the Colorado Cancer Center did three biopsies of tumors taken from a patient who underwent three surgeries for salivary gland cancer. They found that the number of cancer stem cells increased with each surgery. For example, in the first surgery the tumor contained 0.2 percent cancer stem cells. By the third surgery the number of cancer stem cells had risen to 4.5 percent.

Even scarier, the tumor in the third surgery had 50 percent more cancer-driving mutations meaning it was better able to resist attempts to kill it.

In a news release, Dr. Daniel Bowles, the lead investigator, said the tumor seemed to learn and become ever more aggressive:

Bowles headshot

Daniel Bowles

“People talk about molecular evolution of cancer and we were able to show it in this patient. With these three samples, we could see across time how the tumor developed resistance to treatment.”

 

The study is published in the journal Clinical Cancer Research.

New gene associated with ALS identified.
This week, researchers at UMass Medical School and the National Institute on Aging reported the identification of a new gene implicated in the development of amyotrophic lateral sclerosis (ALS). Also known as Lou Gehrig’s disease, ALS is a horrific neurodegenerative disorder that degrades the connection between nerve signals and the muscles. Sufferers are robbed of their ability to move and, ultimately, even to breathe. Life expectancy is just 3 to 5 years after diagnosis.

To identify the gene, called KIF5A, the team carried out the largest genetics effort in ALS research with support from the ALS Association, creators of the Ice Bucket Challenge that raised a $115 million for research. The study compared the genomes between a group of nearly 22,000 people with ALS versus a group of over 80,000 healthy controls. Two independent genetic analyses identified differences in the expression of the KIF5A gene between the two groups.

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Cartoon representing the role that KIF5A plays in neurons. (Image: UMass Medical School)

KIF5A is active in neurons where it plays a key role in transporting cell components across the cell’s axon, the long, narrow portion of the cell that allows neurons to send long-range signals to other cells. It carries out this transport by tethering cell components on the axon’s cytoskeleton, a structural protein matrix within the cells. Several mutations in KIF5A were found in the ALS group which corroborates previous studies showing that mutations in other cytoskeleton genes are associated with ALS.

One next step for the researchers is to further examine the KIF5A mutations using patient-derived induced pluripotent stem cells.

The study was published in Neuron and picked up by Eureka Alert!

Stem Cell Round: Improving memory, building up “good” fat, nanomedicine

Stem Cell Photo of the Week

roundup03618In honor of brain awareness week, our featured stem cell photo is of the brain! Scientists at the Massachusetts General Hospital and Harvard Stem Cell Institute identified a genetic switch that could potentially improve memory during aging and symptoms of PTSD. Shown in this picture are dentate gyrus cells (DGC) (green) and CA3 interneurons (red) located in the memory-forming area of the brain known as the hippocampus. By reducing the levels of a protein called abLIM3 in the DGCs of older mice, the researchers were able to boost the connections between DGCs and CA3 cells, which resulted in an improvement in the memories of the mice. The team believes that targeting this protein in aging adults could be a potential strategy for improving memory and treating patients with post-traumatic stress disorder (PTSD). You can read more about this study in The Harvard Gazette.

New target for obesity.
Fat cells typically get a bad rap, but there’s actually a type of fat cell that is considered “healthier” than others. Unlike white fat cells that store calories in the form of energy, brown fat cells are packed with mitochondria that burn energy and produce heat. Babies have brown fat, so they can regulate their body temperature to stay warm. Adults also have some brown fat, but as we get older, our stores are slowly depleted.

In the fight against obesity, scientists are looking for ways to increase the amount of brown fat and decrease the amount of white fat in the body. This week, CIRM-funded researchers from the Salk Institute identified a molecule called ERRg that gives brown fat its ability to burn energy. Their findings, published in Cell Reports, offer a new target for obesity and obesity-related diseases like diabetes and fatty liver disease.

The team discovered that brown fat cells produce the ERRg molecule while white fat cells do not. Additionally, mice that couldn’t make the ERRg weren’t able to regulate their body temperature in cold environments. The team concluded in a news release that ERRg is “involved in protection against the cold and underpins brown fat identity.” In future studies, the researchers plan to activate ERRg in white fat cells to see if this will shift their identity to be more similar to brown fat cells.

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Mice that lack ERR aren’t able to regulate their body temperature and are much colder (right) than normal mice (left). (Image credit Salk Institute)

Tale of two nanomedicine stories: making gene therapies more efficient with a bit of caution (Todd Dubnicoff).
This week, the worlds of gene therapy, stem cells and nanomedicine converged for not one, but two published reports in the journal American Chemistry Society NANO.

The first paper described the development of so-called nanospears – tiny splinter-like magnetized structures with a diameter 5000 times smaller than a strand of human hair – that could make gene therapy more efficient and less costly. Gene therapy is an exciting treatment strategy because it tackles genetic diseases at their source by repairing or replacing faulty DNA sequences in cells. In fact, several CIRM-funded clinical trials apply this method in stem cells to treat immune disorders, like severe combined immunodeficiency and sickle cell anemia.

This technique requires getting DNA into diseased cells to make the genetic fix. Current methods have low efficiency and can be very damaging to the cells. The UCLA research team behind the study tested the nanospear-delivery of DNA encoding a gene that causes cells to glow green. They showed that 80 percent of treated cells did indeed glow green, a much higher efficiency than standard methods. And probably due to their miniscule size, the nanospears were gentle with 90 percent of the green glowing cells surviving the procedure.

As Steve Jonas, one of the team leads on the project mentions in a press release, this new method could bode well for future recipients of gene therapies:

“The biggest barrier right now to getting either a gene therapy or an immunotherapy to patients is the processing time. New methods to generate these therapies more quickly, effectively and safely are going to accelerate innovation in this research area and bring these therapies to patients sooner, and that’s the goal we all have.”

While the study above describes an innovative nanomedicine technology, the next paper inserts a note of caution about how experiments in this field should be set up and analyzed. A collaborative team from Brigham and Women’s Hospital, Stanford University, UC Berkeley and McGill University wanted to get to the bottom of why the many advances in nanomedicine had not ultimately led to many new clinical trials. They set out looking for elements within experiments that could affect the uptake of nanoparticles into cells, something that would muck up the interpretation of results.

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imaging of female human amniotic stem cells incubated with nanoparticles demonstrated a significant increase in uptake compared to male cells. (Green dots: nanoparticles; red: cell staining; blue: nuclei) Credit: Morteza Mahmoudi, Brigham and Women’s Hospital.

In this study, they report that the sex of cells has a surprising, noticeable impact on nanoparticle uptake. Nanoparticles were incubated with human amniotic stem cells derived from either males or females. The team showed that the female cells took up the nanoparticles much more readily than the male cells.  Morteza Mahmoudi, PhD, one of the authors on the paper, explained the implications of these results in a press release:

“These differences could have a critical impact on the administration of nanoparticles. If nanoparticles are carrying a drug to deliver [including gene therapies], different uptake could mean different therapeutic efficacy and other important differences, such as safety, in clinical data.”

 

Stem Cell Roundup: No nerve cells for you, old man; stem cells take out the trash; clues to better tattoo removal

Stem cell image of the week: Do they or don’t they? The debate on new nerve cell growth in adult brain rages on.

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Young neurons (green) are shown in the human hippocampus at the ages of (from left) birth, 13 years old and 35 years old. Images by Arturo Alvarez-Buylla lab

For the longest time, it was simply a given among scientists that once you reach adulthood, your brain’s neuron-making days were over. Then, over the past several decades, evidence emerged that the adult brain can indeed make new neurons, in a process called neurogenesis. Now the pendulum of understanding may be swinging back based on research reported this week out of Arturo Alvarez-Buylla’s lab at UCSF.

Through the careful examination of 59 human brain samples (from post mortem tissue and those collected during epilepsy surgery), Alvarez-Buylla’s team in collaboration with many other labs around the world, found lots of neurogenesis in neonatal and newborn brains. But after 1 year of age, a steep drop in the number of new neurons was observed. Those numbers continued to plummet through childhood and were barely detectable in samples from teens. New neurons were undetectable in adult brain samples.

This week’s stem cell image shows this dramatic decline of new neurons when comparing brain samples from a newborn, a 13 year-old and a 35 year-old.

It was no surprise that these surprising results, published in Nature, got quite a bit of attention by a wide range of news outlets including the LA Times, CNN, The Scientist and NPR to name just a few.

Limitless life of stem cells requires taking out the trash

It’s minding blowing to me that, given the proper nutrients, an embryonic stem cell in a lab dish can exist indefinitely. The legendary fountain of youth that Ponce de León searched in vain for is actually hidden inside these remarkable cells. So how do they do it? It’s a tantalizing question for researchers because the answers could lead to a better understanding of and eventually novel therapies for age-related diseases.

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Cartoon of a proteosome, the cell’s garbage disposal. Image: Wikipedia

A team from the University of Cologne reports this week on a connection between the removal of degraded proteins and the longevity of stem cells. Cells in general use special enzymes to tag wonky proteins for the cellular trash heap, called a proteasome. Without this ability to clean up, unwanted proteins can accumulate and make cells unhealthy, a scenario that is seen in age-related diseases like Alzheimer’s. The research team found that reducing the protein disposal activity in embryonic stem cells disrupted characteristics that are specific to these cells. So, one way stem cells may keep their youthful appearance is by being good about taking out their trash.

The study was published in Scientific Reports and picked up by Science Daily.

Why tattoos stay when your skin cells don’t ( by Kevin McCormack)

We replace our skin cells every two or three weeks. As each layer dies, the stem cells in the skin replace them with a new batch. With that in mind you’d think that a tattoo, which is just ink injected into the skin with a needle, would disappear as each layer of skin is replaced. But obviously it doesn’t. Now some French researchers think they have figured out why.

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Thank your macrophages for keeping your tattoo intact. Tattoo by: Sansanana

It’s not just fun science, published in the Journal of Experimental Medicine, it could also mean that that embarrassing tattoo you got saying you would love Fred or Freda forever, can one day be easily removed.

The researchers found that when the tattoo needle inflicts a wound on the skin, specialized cells called macrophages flock to the site and take up the ink. As those macrophages die, instead of the ink disappearing with them, new macrophages come along, gobble up the ink and so the tattoo lives on.

In an interview with Health News Digest, Bernard Malissen, one of the lead investigators, says the discovery, could help erase a decision made in a moment of madness:

“Tattoo removal can be likely improved by combining laser surgery with the transient ablation of the macrophages present in the tattoo area. As a result, the fragmented pigment particles generated using laser pulses will not be immediately recaptured, a condition increasing the probability of having them drained away via the lymphatic vessels.”

Stem Cell Roundup: Lab-grown meat, stem cell vaccines for cancer and a free kidney atlas for all

Here are the stem cell stories that caught our eye this week.

Cool Stem Cell Photo: Kidneys in the spotlight

At an early stage, a nephron forming in the human kidney generates an S-shaped structure. Green cells will generate the kidneys’ filtering device, and blue and red cells are responsible for distinct nephron activities. (Image/Stacy Moroz and Tracy Tran, Andrew McMahon Lab, USC Stem Cell)

I had to take a second look at this picture when I first saw it. I honestly thought it was someone’s scientific interpretation of Vincent van Gogh’s Starry Night. What this picture actually represents is a nephron. Your kidney has over a million nephrons packed inside it. These tiny structures filter our blood and remove waste products by producing urine.

Scientists at USC Stem Cell are studying kidney development in animals and humans in hopes of gaining new insights that could lead to improved stem cell-based technologies that more accurately model human kidneys (by coincidence, we blogged about another human kidney study on Tuesday). Yesterday, these scientists published a series of articles in the Journal of American Society of Nephrology that outlines a new, open-source kidney atlas they created. The atlas contains a catalog of high resolution images of different structures representing the developing human kidney.

CIRM-funded researcher Andrew McMahon summed it up nicely in a USC news release:

“Our research bridges a critical gap between animal models and human applications. The data we collected and analyzed creates a knowledge-base that will accelerate stem cell-based technologies to produce mini-kidneys that accurately represent human kidneys for biomedical screening and replacement therapies.”

And here’s a cool video of a developing kidney kindly provided by the authors of this study.

Video Caption: Kidney development begins with a population of “progenitor cells” (green), which are similar to stem cells. Some progenitor cells (red) stream out and aggregate into a ball, the renal vesicle (gold). As each renal vesicle grows, it radically morphs into a series of shapes — can you spot the two S-shaped bodies (green-orange-pink structures)? – and finally forms a nephron. Each human kidney contains one million mature nephrons, which form an expansive tubular network (white) that filters the blood, ensuring a constant environment for all of our body’s functions. (Video courtesy of Nils Lindstorm, Andy McMahon, Seth Ruffins and the Microscopy Core Facility at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at the Keck School of Medicine of USC)


Lab-grown hamburgers coming to a McDonald’s near you…

“Lab-grown meat is coming, whether you like it or not” sure makes a splashy headline! This week, Wired magazine featured two Bay Area startup companies, Just For All and Finless Foods, dedicated to making meat-in-a-dish in hopes of one day reducing our dependence on livestock. The methods behind their products aren’t exactly known. Just For All is engineering “clean meat” from cells. On the menu currently are cultured chorizo, nuggets, and foie gras. I bet you already guessed what Finless Foods specialty is. The company is isolating stem-like muscle progenitor cells from fish meat in hopes of identifying a cell that will robustly create the cell types found in fish meat.

Just’s tacos made with lab-grown chorizo. (Wired)

I find the Wired article particularly interesting because of the questions and issues Wired author Matt Simon raises. Are clean meat companies really more environmentally sustainable than raising livestock? Currently, there isn’t enough data to prove this is the case, he argues. And what about the feasibility of convincing populations that depend on raising livestock for a living to go “clean”? And what about flavor and texture? Will people be willing to eat a hamburger that doesn’t taste and ooze in just the right way?

As clean meat technologies continue to advance and become more affordable, I’ll be interested to see what impact they will have on our eating habits in the future.


Induced pluripotent stem cells could be the next cancer vaccine

Our last story is about a new Cell Stem Cell study that suggests induced pluripotent stem cells (iPSCs) could be developed into a vaccine against cancer. CIRM-funded scientist Joseph Wu and his team at Stanford University School of Medicine found that injecting iPSCs into mice that were transplanted with breast cancer cells reduced the formation of tumors.

The team dug deeper and discovered that iPSCs shared similarities with cancer cells with respect to the panel of genes they express and the types of proteins they carry on their cell surface. This wasn’t surprising to them as both cells represent an immature development stage. Because of these similarities, injecting iPSCs primed the mouse’s immune system to recognize and reject similar cells like cancer cells.

The team will next test their approach on human cancer cells in the lab. Joseph Wu commented on the potential future of iPSC-based vaccines for cancer in a Stanford news release:

“Although much research remains to be done, the concept itself is pretty simple. We would take your blood, make iPS cells and then inject the cells to prevent future cancers. I’m very excited about the future possibilities.”

 

Stem Cell Roundup: New infertility tools, helping the 3 blind mice hear and cow ESCs

Cool Stem Cell Image of the Week

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Human egg grown from immature cells in ovarian tissue. (credit: David Albertini)

This week’s Cool Stem Cell Image of the Week comes to us from the lab of reproductive biologist Evelyn Telfer at the University of Edinburgh. Telfer and her team successfully grew human eggs cells from immature ovarian tissue.

This technology could revolutionize the way doctors approach infertility. For instance, when girls and young women undergo chemotherapy for cancer, their eggs are often damaged. By preserving a small piece of ovarian tissue before the cancer treatments, this method could be used to generate eggs later in life for in vitro fertilization. Much more work is necessary to figure out if these eggs are healthy and safe to use to help infertile women.

The study was recently published in Molecular Human Reproduction and was picked up this Science writer Kelly Servick.

Forget 3 blind mice, iPS cells could help 3 deaf mice hear again (Kevin McCormack)
For years scientists have been trying to use stem cells to restore hearing to people who are deaf or hearing impaired. Now a group of researchers in Japan may have found a way.

The team used human iPS cells to create inner ear cells, the kind damaged in one of the most common forms of hereditary deafness. They then transplanted them into the inner ears of mice developing in the womb that are suffering from a congenital form of hearing loss. The cells appeared to engraft and produce a protein, Connexin 30, known to be critical in hearing development.

The research, published in the journal Scientific Reports, could be an important step towards developing a therapy for congenital hearing loss in people.

UC Davis team isolates cow embryonic stem cells for the first time

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An early stage cow embryo. Inner cell mass (red) is source of embryonic stem cells. (Credit: Pablo Ross/UC Davis) 

Although human embryonic stem cells (ESCs) were isolated way back in ’98, researchers haven’t had similar luck with embryonic stem cells from cows. Until this week, that is.  A UC Davis team just published a report in PNAS showing that they not only can isolate cow ESCs but their method works almost 100% of the time.

 

Genetic engineering of these cow stem cells could have huge implications for the cattle industry. Senior author Pablo Ross mentioned in a press release how this breakthrough could help speed up the process of generating superior cows that produce more milk, release less methane and are more resistant to disease:

“In two and a half years, you could have a cow that would have taken you about 25 years to achieve. It will be like the cow of the future. It’s why we’re so excited about this.”

These cow ESCs may also lead to better models of human disease. Because of their small size, rat and mouse models are not always a good representation of how potential therapies or drugs will affect humans. Creating stem cell models from larger animals may provide a better representation.

Stem Cell Roundup: Rainbow Sherbet Fruit Fly Brains, a CRISPR/iPSC Mash-up and more

This week’s Round Up is all about the brain with some CRISPR and iPSCs sprinkled in:

Our Cool Stem Cell Image of the Week comes from Columbia University’s Zuckerman Institute:

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(Credit: Jon Enriquez/Mann Lab/Columbia’s Zuckerman Institute).

This rainbow sherbet-colored scientific art is a microscopy image of a fruit fly nervous system in which brain cells were randomly labeled with different colors. It was a figure in a Neuron study published this week showing how cells derived from the same stem cells can go down very different developmental paths but then later are “reunited” to carry out key functions, such as in this case, the nervous system control of leg movements.


A new therapeutic avenue for Parkinson’s diseaseBuck Institute

Many animal models of Parkinson’s disease are created by mutating specific genes to cause symptoms that mimic this incurable, neurodegenerative disorder. But, by far, most cases of Parkinson’s are idiopathic, a fancy term for spontaneous with no known genetic cause. So, researchers at the Buck Institute took another approach: they generated a mouse model of Parkinson’s disease using the pesticide, paraquat, exposure to which is known to increase the risk of the idiopathic form of Parkinson’s.

Their CIRM-funded study in Cell Reports showed that exposure to paraquat leads to cell senescence – in which cells shut down and stop dividing – particularly in astrocytes, brain cells that support the function of nerve cells. Ridding the mice of these astrocytes relieved some of the Parkinson’s like symptoms. What makes these results so intriguing is the team’s analysis of post-mortem brains from Parkinson’s patients also showed the hallmarks of increased senescence in astrocytes. Perhaps, therapeutic approaches that can remove senescent cells may yield novel Parkinson’s treatments.


Discovery may advance neural stem cell treatments for brain disordersSanford-Burnham Prebys Medical Discovery Institute (via Eureka Alert)

Another CIRM-funded study published this week in Nature Neuroscience may also help pave the way to new treatment strategies for neurologic disorders like Parkinson’s disease. A team at Sanford Burnham Prebys Medical Discovery Institute (SBP) discovered a novel gene regulation system that brain stem cells use to maintain their ability to self-renew.

The study centers around messenger RNA, a molecular courier that transcribes a gene’s DNA code and carries it off to be translated into a protein. The team found that the removal of a chemical tag on mRNA inside mouse brain stem cells caused them to lose their stem cell properties. Instead, too many cells specialized into mature brain cells leading to abnormal brain development in animal studies. Team lead Jing Crystal Zhao, explained how this finding is important for future therapeutic development:

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Crystal Zhao

“As NSCs are increasingly explored as a cell replacement therapy for neurological disorders, understanding the basic biology of NSCs–including how they self-renew–is essential to harnessing control of their in vivo functions in the brain.”


Researchers Create First Stem Cells Using CRISPR Genome ActivationThe Gladstone Institutes

Our regular readers are most likely familiar with both CRISPR gene editing and induced pluripotent stem cell (iPSC) technologies. But, in case you missed it late last week, a Cell Stem Cell study out of Sheng Ding’s lab at the Gladstone Institutes, for the first time, combined the two by using CRISPR to make iPSCs. The study got a lot of attention including a review by Paul Knoepfler in his blog The Niche. Check it out for more details!

 

Stem Cell RoundUp: CIRM Clinical Trial Updates & Mapping Human Brain

It was a very CIRMy news week on both the clinical trial and discovery research fronts. Here are some the highlights:

Stanford cancer-fighting spinout to Genentech: ‘Don’t eat me’San Francisco Business Times

Ron Leuty, of the San Francisco Business Times, reported this week on not one, but two news releases from CIRM grantee Forty Seven, Inc. The company, which originated from discoveries made in the Stanford University lab of Irv Weissman, partnered with Genentech and Merck KGaA to launch clinical trials testing their drug, Hu5F9-G4, in combination with cancer immunotherapies. The drug is a protein antibody that blocks a “don’t eat me” signal that cancer stem cells hijack into order to evade destruction by a cancer patient’s immune system.

Genentech will sponsor two clinical trials using its FDA-approved cancer drug, atezolizumab (TECENTRIQ®), in combination with Forty Seven, Inc’s product in patients with acute myeloid leukemia (AML) and bladder cancer. CIRM has invested $5 million in another Phase 1 trial testing Hu5F9-G4 in AML patients. Merck KGaA will test a combination treatment of its drug avelumab, or Bavencio, with Forty-Seven’s Hu5F9-G4 in ovarian cancer patients.

In total, CIRM has awarded Forty Seven $40.5 million in funding to support the development of their Hu5F9-G4 therapy product.


Novel regenerative drug for osteoarthritis entering clinical trialsThe Scripps Research Institute

The California Institute for Biomedical Research (Calibr), a nonprofit affiliate of The Scripps Research Institute, announced on Tuesday that its CIRM-funded trial for the treatment of osteoarthritis will start treating patients in March. The trial is testing a drug called KA34 which prompts adult stem cells in joints to specialize into cartilage-producing cells. It’s hoped that therapy will regenerate the cartilage that’s lost in OA, a degenerative joint disease that causes the cartilage that cushions joints to break down, leading to debilitating pain, stiffness and swelling. This news is particularly gratifying for CIRM because we helped fund the early, preclinical stage research that led to the US Food and Drug Administration’s go-ahead for this current trial which is supported by a $8.4 million investment from CIRM.


And finally, for our Cool Stem Cell Image of the Week….

Genetic ‘switches’ behind human brain evolutionScience Daily

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This artsy scientific imagery was produced by UCLA researcher Luis del la Torre-Ubieta, the first author of a CIRM-funded studied published this week in the journal, Cell. The image shows slices of the mouse (bottom middle), macaque monkey (center middle), and human (top middle) brain to scale.

The dramatic differences in brain size highlights what sets us humans apart from those animals: our very large cerebral cortex, a region of the brain responsible for thinking and complex communication. Torre-Ubieta and colleagues in Dr. Daniel Geschwind’s laboratory for the first time mapped out the genetic on/off switches that regulate the growth of our brains. Their results reveal, among other things, that psychiatric disorders like schizophrenia, depression and Attention-Deficit/Hyperactivity Disorder (ADHD) have their origins in gene activity occurring in the very earliest stages of brain development in the fetus. The swirling strings running diagonally across the brain slices in the image depict DNA structures, called chromatin, that play a direct role in the genetic on/off switches.