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.

CIRM’s Industry Alliance Program: Facilitating Partnerships to Advance Stem Cell Therapies

Some things are better together. Take for instance macaroni and cheese, eggs and bacon, cookies and ice cream. Each of these things are fine on their own, but together, they become something more powerful and delicious.

The right partnerships can bring out the best in things. At CIRM, we fully embrace this concept. That’s why we’re launching the Industry Alliance Program (IAP). It’s a new partnering opportunity to bring the most promising stem cell, gene therapy, and regenerative medicine programs to market where they can help people with unmet medical needs.

CIRM is the world’s largest stem cell research funding institution dedicated to helping patients by accelerating the development of quality stem cell treatments. We’re currently funding 244 active stem cell research programs including 39 ongoing clinical trials.

The CIRM IAP is designed to give pharma, biotech and VC firms direct access to CIRM’s growing stem cell portfolio. These partners work in the stem cell and regenerative medicine field and will be connected to CIRM-funded scientists working on projects relevant to their interests.

In a news release, CIRM’s President and CEO, Dr. Maria T. Millan, explained:

Maria T. Millan

“The goal of the IAP is to secure industry partnerships and funding for CIRM’s translational and clinical-stage projects. Our Agency provides researchers the initial funding to advance promising projects towards the clinic. Now, we’re going a step further by offering a program that facilitates connections between industry partners and our grantees. These companies can offer support or additional funding needed to give these promising projects the best chance for success and the best chance of helping patients.”

The first two companies to join the IAP are BlueRock Therapeutics and Vivo Capital. BlueRock is a Cambridge, Massachusetts-based company that is pioneering cell therapies for degenerative diseases while Vivo Capital is a global venture capital firm that invests in life sciences and healthcare companies.

CIRM will continue to selectively recruit new partners to the IAP with the goal of building a collaborative network to support the development and commercialization of CIRM-funded programs.

Neil Littman, CIRM’s Director of Business Development, concluded:

Neil Littman

“The IAP is essentially a built-in concierge service for the stem cell space. Our unique vantage-point both inside and outside of California – spanning discovery, translation, and clinical trials – allows us to effectively match CIRM-funded programs with the strategic objectives of our IAP partners.  We’re excited to work with partners such as BlueRock and Vivo who have a demonstrated commitment to advance stem cell-based therapies to the market.”

For more information about CIRM’s new IAP program, visit our website.

Encouraging news about CIRM-funded clinical trial targeting vision loss

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An eye affected by dry age-related macular degeneration

Dry age-related macular degeneration (AMD) is the leading cause of vision loss in the U.S. By 2020 it’s estimated that as many as three million Americans will be affected by the disease. Right now, there is no effective therapy. But that could change. A new CIRM-funded clinical trial is showing promise in helping people battling the disease not just in stabilizing their vision loss, but even reversing it.

In AMD, cells in the retina, the light-sensitive tissue at the back of the eye, are slowly destroyed affecting a person’s central vision. It can make it difficult to do everyday activities such as reading or watching TV and make it impossible for a person to drive.

Researchers at the University of Southern California (USC) Roski Eye Institute at the Keck School of Medicine, and Regenerative Patch Technologies, have developed a therapy using embryonic stem cells that they turned into retinal pigment epithelium (RPE) cells – the kind of cell destroyed by AMD. These cells were then placed on a synthetic scaffold which was surgically implanted in the back of the eye.

Imaging studies showed that the RPE cells appeared to integrate well into the eye and remained in place during follow-up tests 120 to 365 days after implantation.

Encouraging results

Of the five patients enrolled in the Phase 1/2a trial, four maintained their vision in the treated eye, two showed improvement in the stability of their vision, and one patient had a 17-letter improvement in their vision on a reading chart. In addition, there were no serious side effects or unanticipated problems.

There were other indications the implants were proving beneficial.  People with normal vision have the ability to focus their gaze on a single location. People with advanced AMD lose that ability. In this trial, two of the patients recovered stable fixation. These improvements were maintained in follow-up tests.

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Abla Creasey, Ph.D., CIRM’S Vice President of Therapeutics and Strategic Infrastructure says even these small benefits are important:

“Having a therapy with a favorable safety profile, that could slow down the progression, or even reverse the vision loss would benefit millions of Americans. That’s why these results, while still in an early stage are encouraging, because the people treated in the trial are ones most severely affected by the disease who have the least potential for visual recovery.”

This study reflects CIRM’s long-term commitment to supporting the most promising stem cell research. The Stem Cell Agency began supporting USC’s Dr. Mark Humayun, the lead inventor of the implant, in 2010 and has been a partner with him and his team since then.

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In a news release Dr. Humayun said they plan to recruit another 15 patients to see if these results hold up:

“Our study shows that this unique stem cell–based retinal implant thus far is well-tolerated, and preliminary results suggest it may help people with advanced dry age-related macular degeneration.”

While the results, published in the journal Science Translational Medicine, are encouraging the researchers caution that this was a very early stage clinical trial, with a small number of patients. They say the next step is to continue to follow the four patients treated in this trial to see if there are any further changes to their vision, and to conduct a larger trial.

 

 

UC Davis researchers make stem cell-derived mini-brains that contain blood vessels

Growing neurons on a flat petri dish is a great way to study the inner workings of nerve signals in the brain. But I think it’s safe to argue that a two-dimensional lawn of cells doesn’t capture all the complexity of our intricate, cauliflower-shaped brains. Then again, cracking open the skulls of living patients is also not a viable path for fully understanding the molecular basis of brain disorders.

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Brain organoids (two white balls) growing in petri dish.
Image: Pasca Lab, Stanford University.

The recent emergence of stem cell-derived mini-brains, or brain organoids, as a research tool is bridging this impasse. With induced pluripotent stem cells (iPSCs) derived from a readily-accessible skin sample from patients, it’s possible to generate three-dimensional balls of cells that mimic particular parts of the brain’s anatomy. These mini-brains have the expected type of neurons, as well as other cells that support neuron function. We’ve written many blogs, most recently in January, on the applications of this cutting-edge tool.

With any new technology, there is always room for improvement. One thing that most mini-brains lack is their own system of blood vessels, or vasculature. That’s where Dr. Ben Waldau, a vascular neurosurgeon at UC Davis Medical Center, and his lab come into the picture. Last week, their published work in NeuroReport showed that incorporating blood vessels into a brain organoid is possible.

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A stained cross-section of a brain organoid showing that blood vessels (in red) have penetrated both the outer, more organized layers and the inner core. Image: UC Davis Institute for Regenerative Cures

Using iPSCs from one patient, the Waldau team separately generated brain organoids and blood vessels cells, also called endothelial cells. After growing each for about a month, the organoids were embedded in a gelatin containing the endothelial cells. In an excellent Wired article, writer Megan Molteni explains what happened next:

“After incubating for three weeks, they took a single organoid and transplanted it into a tiny cavity carefully carved into a mouse’s brain. Two weeks later the organoid was alive, well—and, critically, had grown capillaries that penetrated all the way to its inner layers.”

Every tissue relies on nutrients and oxygen from the blood. As Molteni suggests, being able to incorporate blood vessels and brain organoids from the same patient’s cells may make it possible to grow and study even more complex brain structures without the need of a mouse using fluidic pumps.

As Waldau explains in the Wired article, this vascularized brain organoid system also adds promise to the ultimate goal of repairing damaged brain tissue:

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Ben Waldau

“The whole idea with these organoids is to one day be able to develop a brain structure the patient has lost made with the patient’s own cells. We see the injuries still there on the CT scans, but there’s nothing we can do. So many of them are left behind with permanent neural deficits—paralysis, numbness, weakness—even after surgery and physical therapy.”

 

 

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.

East Coast Company to Sell Research Products Derived from CIRM’s Stem Cell Bank

With patient-derived induced pluripotent stem cells (iPSCs) in hand, any lab scientist can follow recipes that convert these embryonic-like stem cells into specific cell types for studying human disease in a petri dish. iPSCs derived from a small skin sample from a Alzheimer’s patient, for instance, can be specialized into neurons – the kind of cell affected by the disease – to examine what goes wrong in an Alzheimer’s patient’s brain or screen drugs that may alleviate the problems.

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Neurons created from Alzheimer’s disease patient-derived iPSCs.
Image courtesy Elixirgen Scientific

But not every researcher has easy access to a bank of patient-derived iPSCs and it’s not trivial to coax iPSCs to become a particular cell type. The process is also a time sink and many scientists would rather spend that time doing what they’re good at: uncovering new insights into their disease of interest.

Since the discovery of iPSC technology over a decade ago, countless labs have worked out increasingly efficient variations on the original method. In fact, companies that deliver iPSC-derived products have emerged as an attractive option for the time-strapped stem cell researcher.

One of those companies is Elixirgen Scientific of Baltimore, Maryland. Pardon the pun but Elixirgen has turned the process of making various cell types from iPSCs into a science. Here’s how CEO Bumpei Noda described the company’s value to me:

Bumpei-Noda-200

Bumpei Noda

“Our technology directly changes stem cells into the cells that make up most of your body, such as muscle cells or neural cells, in about one week. Considering that existing technology takes multiple weeks or even months to do the same thing, imagine how much more research can get done than before.”

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With Elixirgen’s technology, different “cocktails” of ingredients can quickly and efficiently turn iPSCs into many different human cell types. Image courtesy Elixirgen Scientific

Their technology is set to become an even greater resource for researchers based on their announcement yesterday that they’ve signed a licensing agreement to sell human disease cells that were generated from CIRM’s iPSC Repository.

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Stephen Lin

“The CIRM Repository holds the largest publicly accessible collection of human iPSCs in the world and is the result of years of coordinated efforts of many groups to create a leading resource for disease modeling and drug discovery using stem cells,” said Stephen Lin, a CIRM Senior Science Officer who oversees the cell bank.

 

The repository currently contains a collection of 1,600 cell lines derived from patients with diseases that are a source of active research, including autism, epilepsy, cerebral palsy, Alzheimer’s disease, heart disease, lung disease, hepatitis C, fatty liver disease, and more (visit our iPSC Repository web page for the complete list).

While this wide variety of patient cells lines certainly played a major role in Elixirgen’s efforts to sign the agreement, Noda also noted that the CIRM Repository “has rich clinical and demographic data and age-matched control cell lines” which is key information to have when interpreting the results of experiments and drug screening.

Lin also points out another advantage to the CIRM cells:

“It’s one of the few collections with a streamlined route to commercialization (i.e. pre-negotiated licenses) that make activities like Elixirgen’s possible. iPSC technology is still under patent and technically cannot be used for drug discovery without those legal safeguards. That’s important because if you do discover a drug using iPSCs without taking care of these licensing agreements, your discovery could be owned by that original intellectual property holder.”

At CIRM, we’re laser-focused on accelerating stem cell treatments to patients with unmet medical needs. That’s why we’re excited that Elixirgen Scientific has licensed access to the our iPSC repository. We’re confident their service will help researchers work more efficiently and, in turn, accelerate the pace of new discoveries.

Say Hello to CIRM’s New Active Awards Portfolio Dashboard (Video Included!)

It takes a lot of time, money and effort to develop a promising stem cell research idea into an effective treatment that can help patients. Oftentimes, you don’t hear about the early-stage research that goes into developing a particular treatment until it reaches the clinic.

CIRM recognizes the importance of investing in all stages of stem cell research and has an impressive portfolio of over 160 active projects spanning discovery, translation, and clinical-stage research.

To help you understand the breadth of our funding efforts, and to highlight our expanding research pipeline, we’ve created the Active Awards Portfolio Dashboard on our website. This interactive tool makes it easy to search through the active research projects that we’re currently funding, and filter these projects by disease focus, technology type or stage of research.

Watch the short video below to learn more about our new Dashboard and how to use it.

The Active Awards Dashboard reflects our Agency’s commitment to investing in the full range of stem cell research and to helping the most promising research projects advance to the next level.

For those of you interested in learning more about the 45 active clinical trials we’re funding, be sure to check out the companion Clinical Trials Dashboard on our website, featured previously on the Stem Cellar blog.

Stem Cell Agency Heads to Inland Empire for Free Patient Advocate Event

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I am embarrassed to admit that I have never been to the Inland Empire in California, the area that extends from San Bernardino to Riverside counties.  That’s about to change. On Monday, April 16th CIRM is taking a road trip to UC Riverside, and we’re inviting you to join us.

We are holding a special, free, public event at UC Riverside to talk about the work that CIRM does and to highlight the progress being made in stem cell research. We have funded 45 clinical trials in a wide range of conditions from stroke and cancer, leukemia, lymphoma, vision loss, diabetes and sickle cell disease to name just a few. And will talk about how we plan on funding many more clinical trials in the years to come.

We’ll be joined by colleagues from both UC Riverside, and City of Hope, talking about the research they are doing from developing new imaging techniques to see what is happening inside the brain with diseases like Alzheimer’s, to using a patient’s own cells and immune system to attack deadly brain cancers.

It promises to be a fascinating event and of course we want to hear from you, our supporters, friends and patient advocates. We are leaving plenty of time for questions, so we can hear what’s on your mind.

So, join us at UC Riverside on Monday, April 16th from 12.30pm to 2pm. The doors open at 11am so you can enjoy a poster session (highlighting some of the research at UCR) and a light lunch before the event. Parking will be available on site.

Visit the Eventbrite page we have created for all the information you’ll need about the event, including a chance to RSVP and book your place.

The event is free so feel free to share this with anyone and everyone you think might be interested in joining us.

 

 

Tiny blood vessels in the brain can spur the growth of spinal motor neurons

Last week, researchers from Cedars-Sinai Medical Center added a new piece to the complex puzzle of what causes neurodegenerative disorders like amyotrophic lateral sclerosis (ALS). The team discovered that the tiny blood vessels in our brains do more than provide nutrients to and remove waste products from our brain tissue. It turns out that these blood vessels can stimulate the growth of new nerve cells called spinal motor neurons, which directly connect to the muscles in our body and control how they move. The study, which was funded in part by a CIRM Discovery research-stage Inception award, was published in the journal Stem Cell Reports.

The Cedars team used a combination of human induced pluripotent stem cells (iPSCs) and organ-on-a-chip technology to model the cellular microenvironment of the spinal cord. They matured the iPSCs into both spinal motor progenitor cells and brain endothelial cells (which line the insides of blood vessels). These cells were transferred to an organ-chip where they were able to make direct contact and interact with each other.

Layers of spinal motor neuron cells (top, in blue) and capillary cells (bottom, in red) converge inside an Organ-Chip. Neurons and capillary cells interact together along the length of the chip. (Cedars-Sinai Board of Governors Regenerative Medicine Institute).

The researchers discovered that exposing the spinal motor progenitor cells to the blood vessel endothelial cells in these organ-chips activated the expression of genes that directed these progenitor cells to mature into spinal cord motor neurons.

Hundreds of spinal motor neurons spontaneously communicate through electrical signals inside an Organ-Chip. Neurons fire individually (flashing dots) and in synchronized bursts (bright waves). (Cedars-Sinai)

First author on the study, Samuel Sances, explained their findings in a news release:

“Until now, people thought these blood vessels just delivered nutrients and oxygen, removed waste and adjusted blood flow. We showed that beyond plumbing, they are genetically communicating with the neurons.”

The team also showed the power of stem cell-based organ-chip platforms for modeling diseases like ALS and answering key questions about why these diseases occur.

“What may go wrong in the spinal neurons that causes the motor neurons to die?” Sances asked. “If we can model an individual ALS patient’s tissues, we may be able to answer that question and one day rescue ALS patients’ neurons through new therapies.”

Clive Svendsen, a CIRM grantee and the senior author on the study, said that his team will conduct additional studies using organ-chip technology to study the interactions between iPSC-derived neurons and blood vessels of healthy individuals and ALS patients. Differences in these cellular interactions in diseased patient cells could offer new targets for developing ALS therapies.

The current study is a collaboration between Cedars and a Boston company called Emulate, Inc. Emulate developed the organ-chip technology and is collaborating with Svendsen at Cedars to not only model neurodegenerative diseases, but also model other organ systems. Be sure to check out our recent blog about their efforts to create a stem cell-based gut-on-a-chip, which they hope will pave the way for personalized treatments for patients with gastrointestinal diseases like Chrohn’s and inflammatory bowel disease.

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:

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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!