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.


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.


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.


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.


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.


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.


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


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


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:


(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:


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


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.

Stem Cell Roundup: Gene therapy for diabetes, alcohol is bad for your stem cells and hairy skin

The start of a new year is the perfect opportunity to turn a new leaf. I myself have embraced 2018 with open arms and decided to join my fellow millennials who live and die by the acronym YOLO.

How am I doing this? Well, so far, I got a new haircut, I started doing squats at the gym, and I’m changing up how we blog on the Stem Cellar!

On Fridays, we always share the stem cell stories that “caught our eye” that week. Usually we pick three stories and write short blogs about each of them. Over time, these mini-blogs have slowly grown in size to the point where sometimes we (and I’m sure our readers) wonder why we’re trying to pass off three blogs as one.

Our time-honored tradition of telling the week’s most exciting stem cell stories on Friday will endure, but we’re going to change up our style and give you a more succinct, and comprehensive roundup of stem cell news that you be on your radar.

To prove that I’m not all talk, I’m starting off our new Roundup today. Actually, you’re reading it right now. But don’t worry, the next one we do won’t have this rambling intro 😉.

So here you go, this week’s eye-catching stem cell stories in brief:

Gene therapy helps mice with type 1 diabetesEurekAlert!

A study in Cell Stem Cell found that gene therapy can be used to restore normal blood sugar levels in mice with type 1 diabetes. The scientists used a virus to deliver two genes, PDX1 and MAFA, into non-insulin producing pancreatic cells. The expression of these two proteins, reprogrammed the cells into insulin-producing beta cells that stabilized the blood sugar levels of the mice for 4 months. While the curative effects of the gene therapy weren’t permanent, the scientists noted that the reprogrammed beta cells didn’t trigger an immune response, indicating that the cells acted like normal beta cells. The researchers will next test this treatment in primates and if it works and is safe, they will move onto clinical trials in diabetic patients.

Alcohol increases cancer risk in mice by damaging stem cell DNA – GenBio

*Fair warning for beer or wine lovers: you might not want to read story.

Cambridge scientists published a study in Nature that suggests a byproduct of alcohol called acetaldehyde is toxic to stem cells. They gave watered-down alcohol to mice lacking an essential enzyme that breaks down alcohol in the liver. They found that the DNA in the blood-forming stem cells of the mice lacking this enzyme were four times more damaged than the DNA of normal mice. Excessive DNA damage creates instability in the genetic material of cells, which, over time, can lead to cancer. While many things can cause cancer, individuals who aren’t able to process alcohol effectively should take this study into consideration.

Stem cell therapy success for sclerodoma patientsThe Niche

For those of you unfamiliar with sclerodoma, it’s an autoimmune disease that can affect the skin, blood vessels, muscle tissue and organs in the body. Rather than recreate the wheel, here’s an overview of this study by UC Davis Professor Paul Knoepfler in his blog called The Niche:

Paul Knoepfler

A new NIH-funded study reported in the New England Journal of Medicine (NEJM) gives some hope for the use of a combination of a specific type of myeloablation [a form of chemotherapy] and a transplant of hematopoietic stem cells. This approach yields improved long-term outcomes for patients with a severe form of scleroderma called systemic sclerosis. While survival rates for systemic sclerosis have improved it remains a very challenging condition with a significant mortality rate.”

Phase III stem cell trial for osteoarthritis starts in JapanEurekAlert!

Scientists in Japan have developed a stem cell-based therapy they hope will help patients with osteoarthritis – a degenerative joint disease that causes the breakdown of cartilage. The therapy consists of donor mesenchymal stem cells from a commercial stem cell bank. The team is now testing this therapy in a Phase III clinical trial to assess the therapy’s safety and effectiveness. As a side note, CIRM recently funded a clinical trial for osteoarthritis run by a company called CALIBR. You can read more about it here.

Cool Stem Cell Photo of the Week

I’ll leave you with this rad photo of hairy skin made from mouse pluripotent stem cells. You can read about the study that produced these hairy skin organoids here.

In this artwork, hair follicles grow radially out of spherical skin organoids, which contain concentric epidermal and dermal layers (central structure). Skin organoids self-assemble and spontaneously generate many of the progenitor cells observed during normal development, including cells expressing the protein GATA3 in the hair follicles and epidermis (red). Credit: Jiyoon Lee and Karl R. Koehler

Stem Cell Stories that Caught Our Eye: GPS for Skin & Different Therapies for Aging vs. Injured Muscles?

Skin stem cells specialize into new skin by sensing neighborhood crowding
When embarking on a road trip, the GPS technology inside our smartphones helps us know where we are and how to get where we’re going. The stem cells buried in the deepest layers of our skin don’t have a GPS and yet, they do just fine determining their location, finding their correct destination and becoming the appropriate type of skin cell. And as a single organ, all the skin covering your body maintains the right density and just the right balance of skin stem cells versus mature skin cells as we grow from a newborn into adult.


Skin cells growing in a petri dish (green: cytoskeleton, red: cell-cell junction protein).
Credit: MPI for Biology of Aging

This easily overlooked but amazing feat is accomplished as skin cells are continually born and die about every 30 days over your lifetime. How does this happen? It’s an important question to answer considering the skin is our first line of defense against germs, toxins and other harmful substances.

This week, researchers at the Max Planck Institute for Biology of Aging in Cologne, Germany reported a new insight into this poorly understood topic. The team showed that it all comes down to the skin cells sensing the level of crowding in their local environment. As skin stem cells divide, it puts the squeeze on neighboring stem cells. This physical change in tension on these cells “next door” triggers signals that cause them to move upward toward the skin surface and to begin maturing into skin cells.

Lead author Yekaterina Miroshnikova explained in a press release the beauty of this mechanism:

“The fact that cells sense what their neighbors are doing and do the exact opposite provides a very efficient and simple way to maintain tissue size, architecture and function.”

The research was picked up by Phys.Org on Tuesday and was published in Nature Cell Biology.

Stem cells respond differently to aging vs. injured muscle
From aging skin, we now move on to our aging and injured muscles, two topics I know oh too well as a late-to-the-game runner. Researchers at the Sanford Burnham Prebys Medical Discovery Institute (SBP) in La Jolla report a surprising discovery that muscle stem cells respond differently to aging versus injury. This important new insight could help guide future therapeutic strategies for repairing muscle injuries or disorders.

muscle stem cell

Muscle stem cell (pink with green outline) sits along a muscle fiber.
Image: Michael Rudnicki/OIRM

Muscle stem cells, also called satellite cells, make a small, dormant population of cells in muscle tissue that springs to life when muscle is in need of repair. It turns out that these stem cells are not identical clones of each other but instead are a diverse pool of cells.  To understand how the assortment of muscle stem cells might respond differently to the normal wear and tear of aging, versus damage due to injury or disease, the research team used a technology that tracks the fate of individual muscle stem cells within living mice.

The analysis showed a clear but unexpected result. In aging muscle, the muscle stem cells maintained their diversity but their ability to divide and grow declined. However, the opposite result was observed in injured muscle: the muscle stem cell diversity became limited but the capacity to divide was not affected. In a press release, team leader Alessandra Sacco explains the implications of these findings for therapy development:


Alessandra Sacco, PhD

“This study has shown clear-cut differences in the dynamics of muscle stem cell pools during the aging process compared to a sudden injury. This means that there probably isn’t a ‘one size fits all’ approach to prevent the decline of muscle stem cells. Therapeutic strategies to maintain muscle mass and strength in seniors will most likely need to differ from those for patients with degenerative diseases.”

This report was picked up yesterday by Eureka Alert and published in Cell Stem Cell.

Stem Cell Stories that Caught our Eye: Mini-Brains in the Spotlight

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

Two research photos really caught my eye this week and they happened to be of the same thing – mini-brains. Also referred to as brain organoids, mini-brains are tiny balls of nervous tissue grown from stem cells in the lab. They allow scientists to model early brain development and study how disease affects brain cells. Another awesome thing about mini-brains is how cool they look under a microscope.

Mini Brains Part 1

Mini-brain grown in a culture dish. (Photo by Collin Edington and Iris Lee, MIT)

I discovered the first photo in a blog by Dr. Francis Collins, the Director of the National Institutes of Health. He was featuring one of the winning images from the 2017 Koch Institute Image Awards at MIT. The mini-brain photo was taken by researchers Collin Edington and Iris Lee and took over 12 hours to make. Talk about dedication!

Collins revealed that growing mini-brains from stem cells is just the tip of the iceberg for this MIT team. The researchers have plans to grow other types of mini-organs and eventually combine them to make a “human on a chip”. This multi-organ technology will be extremely valuable for studying complex diseases like Alzheimer’s and Parkinson’s, which affect multiple systems in the body.

Mini Brains Part 2

Mini-brain. (Photo by Robert Krencik and Jessy Van Asperen)

The second photo of mini-brains is from a study published this week in Stem Cell Reports by researchers at the Houston Methodist Research Institute. The team has developed a more efficient and effective method for growing mini-brains from stem cells. Typically, the process takes weeks to grow the organoids and months to mature those organoids to the point where they develop the specific cell types and structures found in the human brain.

The Houston team found that maturing different types of brain cells from pluripotent stem cells separately and then combining these mature cells together produced mini-brains that more accurately represented the complexity of the human brain. The trick was to add the brain’s support cells, called astrocytes, to the mini-brains. The astrocytes effectively “accelerated the connections of the surrounding neurons.”

The studies first author, Robert Krencik, explained in a news release,

“We always felt like what we were doing in the lab was not precisely modeling how the cells act within the human brain. So, for the first time, when we put these cells together systematically, they dramatically changed their morphological complexity, size and shape. They look like cells as you would see them within the human brain, so now we can study cells in the lab in a more natural environment.”

Their method also cuts down the time it takes to make mini-brains which will hugely benefit neuroscience researchers who have passed on using mini-brains in their studies because of the cost and time it takes to grow them. Krencik explained,

“Normally, growing these 3-D mini brains takes months and years to develop. We have new techniques to pre-mature the cells separately and then combine them, and we found that within a few weeks they’re able to form mature interactions with each other. So, the length of time to get to that endpoint for studies is dramatically reduced with our system.”

The team plans to use this method to make patient-specific mini-brains from induced pluripotent stem cells to gain new insights into how disease affects the brain. They also hope to translate their mini-brain system into clinical trials to help patients regenerate brain damage or repair brain function.