School’s Out! Stem cells are in! High school students start CIRM-funded summer research internships.

Robotic engineering, coding, video game design, filmmaking, soccer and swimming: these are just a few of the many activities that are vying for the attention of high school students once school lets out for the summer.

But a group of about 50 high schoolers in California have chosen a different path: they will be diving into the world of stem cell biology. Each student earned a spot in one of seven CIRM-funded SPARK Programs across California. That’s short for Summer Program to Accelerate Regenerative Medicine Knowledge (yes, technically it should be SPARMK but we like SPARK better).

The SPARK students will gain hands-on training in stem cell research at some of the leading research institutes in California by conducting a six-week research internship in a stem cell lab. Maybe I’m bias, as the Program Director at CIRM who oversees the SPARK programs, but I think they’ve made a great decision. Stem cell research is one of, if not the most exciting and cutting-edge fields of research science out there today.

The pace of progress is so rapid in the field that a large workforce over the next century is critical to sustain CIRM’s mission to accelerate stem cell treatments to patients with unmet medical needs. That’s why the Agency has invested over $4 million to support over 400 SPARK interns since 2012.

Yesterday, I had the pleasure to be in Sacramento to welcome the UC Davis SPARK interns on their first day of their program which is led by Gerhard Bauer, director of the Good Manufacturing Practice (GMP) laboratory at the UC Davis Institute for Regenerative Cures. The other programs, like the one at Cedars-Sinai in Los Angeles (see photo below), are also starting this week or next.

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Because everything we do at CIRM is focused on the patient, the SPARK programs are required to include patient engagement as part of the students’ internships. Here are some Instagram posts from last year that highlight those patient-centered activities.

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And speaking of Instagram, we have also included a social media component to the program. We believe it’s critical for scientists to connect with the public about the important work they do. During the UC Davis orientation, Jan Nolta, PhD, the director of the Stem Cell Program at UC Davis School of Medicine, pointed out to the students that making the science accessible and understandable to the public, makes stem cell research less scary and, as a result, it’s more likely to gain public support.

So, as part of their curriculum, the interns will share a few Instagrams per week that capture their summer in the lab. You can follow their posts at #CIRMSPARKLab. In addition to communicating through photos, the students will describe their internship experiences by writing a blog. We’ll post the most outstanding blogs later this summer. In the meantime, you can read last summer’s winning blogs.

At the end of their program, the students get to show off their hard work by presenting their research at the SPARK annual conference which will be held this year at UC Davis. It’s going to be an exciting summer!

A Cowboys Fan’s Take on The Catch and Dwight Clark’s Passing Due to ALS

I grew up in Dallas in the 80’s. Needless to say, I was a diehard fan of the Dallas Cowboys National Football League (NFL) team and January 10, 1982 will forever be seared into my memory. Late in the fourth quarter, the Cowboys were leading the San Francisco 49ers 27-21 in the conference championship with the winner moving on to the Super Bowl. But then, with less than a minute remaining, The Catch happened. Dwight Clark of the 49ers sailed over the Cowboys’ Everson Walls to catch Joe Montana’s game-winning pass in the end zone. I was crushed and had a dark cloud over my head for many days afterward.

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Dwight Clark sails over Everson Walls for The Catch

Though I’ve lived in the Bay Area for the past twenty years and become a 49ers fan, it’s still hard for me to watch video clips of The Catch which is arguably this region’s greatest moment in the history of professional sports. Over the years of listening to sports talk radio, I heard interviews with and about Dwight Clark and have come to realize what a terrific person he was. So, I may hate that play, but I certainly can’t hate the man. That’s why I was as heartbroken as everyone else around here with yesterday’s news that Clark had succumbed, at only 61 years of age, to his battle with amyotrophic lateral sclerosis (ALS) also known as Lou Gehrig’s disease, an incurable neurodegenerative disorder that is usually fatal within 2 to 5 years after diagnosis.

Not surprisingly, the ALS Association’s Golden West Chapter, which covers the entire West Coast, was contacted by every Bay Area TV station about Clark’s death. In her KTVU news segment, TV reporter Deborah Villalon explained what Clark meant to ALS patient advocates who often feel invisible:

“To the ALS community he is a hero for raising awareness in the very public way he faced the disease. Clark faced the terminal illness head-on, speaking publicly of his challenges, even appearing on the big screen at Levi’s Stadium last fall, to thank fans for their support.”

At CIRM, we are funding two clinical trials run by Cedars-Sinai and BrainStorm Cell Therapeutics testing stem cell-based treatments for ALS. In Clark’s memory and for everyone in the ALS community, we hope these trials one day lead to new treatment options for the 5,000 thousand newly diagnosed cases each year in the U.S.

Boosting immune system cells could offer a new approach to treating Lou Gehrig’s disease

ALS

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is one of those conditions that a lot of people know about but don’t know a lot about. If they are fortunate it will stay that way. ALS is a nasty neurodegenerative disease that attacks motor neurons, the cells in the brain and spinal cord that control muscle movement. As the disease progresses the individual loses their ability to walk, talk, eat, move and eventually to breathe. There are no effective treatments and no cure. But now research out of Texas is offering at least a glimmer of hope.

Dr. Stanley Appel, a neurologist at the Houston Methodist Neurological Institute noticed that many of the ALS patients he was treating had low levels of regulatory T cells, also known as Tregs. Tregs play a key role in our immune system, suppressing the action of molecules that cause inflammation and also helping prevent autoimmune disease.

In an article on Health News Digest Appel said:

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Dr. Stanley Appel: Photo courtesy Australasian MND Symposium

“We found that many of our ALS patients not only had low levels of Tregs, but also that their Tregs were not functioning properly. We believed that improving the number and function of Tregs in these patients would affect how their disease progressed.”

And so that’s what he and his team did. They worked with M.D. Anderson Cancer Center’s Stem Cell Transplantation and Cellular Therapy program on a first-in-human clinical trial. They took blood from three people with different stages of ALS, separated the red and white blood cells, and returned the red blood cells to the patient. They then separated the Tregs from the white blood cells, increased their number in the lab, and then reinfused them into the patients, in a series of eight injections over the course of several months.

Their study, which appears in the journal Neurology,® Neuroimmunology & Neuroinflammation, found that the therapy appears to be safe without any serious side effects.

Jason Thonhoff, the lead author of the study, says the therapy also appeared to help slow the progression of the disease a little.

“A person has approximately 150 million Tregs circulating in their blood at any given time. Each dose of Tregs given to the patients in this study resulted in about a 30 to 40 percent increase over normal levels. Slowing of disease progression was observed during each round of four Treg infusions.”

Once the infusions stopped the disease progression resumed so clearly this is not a cure, but it does at least suggest that keeping Tregs at a healthy, high-functioning level may help slow down ALS.

CIRM is funding two clinical trials targeting ALS. One is a Phase 1 clinical trial with Clive Svendsen’s team at Cedars-Sinai Medical Center, the other is a Phase 3 project with Brainstorm Cell Therapeutics.

Meet the high school student who moonlights as a neuroscientist

As part of our CIRM scholar blog series, we’re featuring the research and career accomplishments of CIRM funded students. Today, you’ll read about one of our former SPARK high school students.


Emma Friedenberg and former CIRM SPARK Director Karen Ring at the 2017 SPARK Conference.

Emma Friedenberg is a high school senior at Campbell Hall in North Hollywood, California. She’s also an up-and-coming neuroscientist who has her sights set on unraveling the complexities of the brain and discovering cures for degenerative brain diseases. Emma spent the summer of 2017 studying Huntington’s disease in the lab of Dr. Virginia Mattis at the Cedars-Sinai Medical Center. Her internship was possible because of the CIRM SPARK high school educational program which gives California students the opportunity to do stem cell research for a summer.

Below is an interview with Emma about her SPARK experience and how the program is helping her pursue her passions for research and medicine.

Q: How did you learn about the CIRM SPARK program and why did you want to apply?

I’ve been a clinical volunteer at Cedars-Sinai Medical Center for two years in the Intensive Care Unit and the Neurology and Spine Unit. I was submitting my application to return as a volunteer when I explored Cedars-Sinai’s Outreach website page and found the CIRM SPARK program. I knew immediately it was a perfect fit. I plan on studying neuroscience in college with an intention of obtaining my medical degree and becoming a surgeon. The CIRM SPARK program at Cedars within the Board of Governor’s Regenerative Medicine Institute had an option to be involved specifically in the Brain Program. In Dr. Virginia Mattis’ lab, I studied translational stem cell therapies for neurodegenerative diseases, in particular Huntington’s Disease. As Cedars-Sinai calls it, a “bench to bedside” approach is an unparalleled and invaluable experience and huge advantage in science.

Q: What was your SPARK research project?

At Cedars-Sinai, I was mentored by Dr. Virginia Mattis in her stem cell lab. The Mattis Lab researches stem cell therapies for Huntington’s disease (HD), a neurodegenerative brain disease. HD is caused by a loss of neurons, specifically medium spiny neurons in the striatum of Huntington’s patients. We used induced pluripotent stem cells to model HD in a petri dish to study the development of the disease and to create medium spiny neurons that could one day be transplanted into Huntington’s patients to replace lost and damaged cells.

Medium spiny neurons made from Huntington’s disease patient induced pluripotent stem cells. (Image credit: Mattis Lab, Cedars Sinai)

My primary research in the Mattis Lab was experimenting on our cell line to find the most time and cost-effective procedure to produce large populations of medium spiny neurons, because current methods are expensive and largely inefficient. However, my internship was not limited to the laboratory. I spent a significant amount of time shadowing doctors in the ALS Clinic.

Q: What was your experience in the CIRM SPARK program like?

In one word, the CIRM SPARK program was incredible –a one of a kind opportunity. The sciences are my personal passion and the cornerstone of my academic pursuits. The CIRM SPARK program has bolstered my scientific knowledge and provided practical experience in a real-world laboratory environment. A career in medicine is a significant commitment, and I’m confident the CIRM SPARK program was a beneficial start to obtaining my goals.

Cedars-Sinai SPARK students celebrating the completion of their 2017 internships.

Q: What do you value most about your SPARK experience?

It was wonderful to be part of a program which understood collaboration and offered a plethora of learning opportunities outside of the wet lab. What I will keep with me is not only techniques of immunocytochemistry and microscopy, but also the advice and encouragement from accomplished scientists like Clive Svendsen and my mentor Virginia Mattis.

Q: What are your future goals?

I plan on studying neuroscience in college with an intention of obtaining my medical degree and becoming a surgeon.

Q: Who is your scientific idol and why?

I recently read Dr. Eric Kandel’s book, The Age of Insight: The Quest to Understand the Unconscious in Art, Mind, and Brain, from Vienna 1900 to the Present. Dr. Kandel is a neuroscientist and a Professor at Columbia University. He received the Nobel Prize for his work in memory storage using Aplysia, a type of sea slug. His book examines how the human brain responds to art. What I find so inspiring about his book is his interdisciplinary approach to science, a combination of neuroscience, psychoanalysis, biology, and art. The human brain is so complicated that it can be studied from numerous perspectives, from biology to chemistry to electrophysiology. It is not until we can begin to merge these understandings that we will begin to unlock the secrets of the brain. Dr. Kandel is not only a scientist, but an intellectual.

Q: What is your favorite thing about being a scientist?

For centuries, the human brain was an anomaly, unexplainable by science. With 100 billion neurons and 100 trillion connections, the brain is the most complex network in the universe. How the brain functions as an information-processing organ and regulates emotion, behavior, and cognition as well as basic body functions like breathing remains a mystery. In recent years, there has been significant progress in brain research. Scientists are on the brink of major breakthroughs, but there is significant work to do particularly on neurological brain disorders. Being a scientist means living on the cutting-edge of human innovation. I enjoy being able to both ask and answer questions that will benefit humankind.


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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.

Straight to brain: A better approach to ALS cell therapies?

Getting the go ahead to begin a clinical trial by no means marks an end to a research team’s laboratory studies. A clinical trial is merely one experiment and is designed to answer a specific set of questions about a specific course of treatment. There will inevitably be more questions to pursue back in the lab in parallel with an ongoing clinical trial to potentially enhance the treatment.

That’s the scenario for Cedar-Sinai’s current CIRM-funded clinical trial testing a cell therapy for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. Animal studies published this week in Stem Cells suggests that an additional route of therapy delivery may have potential and should also be considered.

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Microscopy image showing transplanted neural progenitor cells (green), the protein GDNF (red) and motor neurons (blue) together in brain tissue. Credit: Cedars-Sinai Board of Governors Regenerative Medicine Institute

ALS is an incurable disease that destroys motor neurons responsible for communicating muscle movement between the brain and the rest of the body via the spinal cord. ALS sufferers lose the use of their limbs and eventually the muscles that control breathing. They rarely live more than 3 to 5 years after diagnosis.

The CIRM-funded trial uses neural progenitor cells – which are similar to stem cells but can only specialize into different types of brain cells – that are genetically engineered to release a protein called GDNF that helps protect the motor neurons from destruction. These cells are being transplanted into the spinal cords of the clinical trial participants.

While earlier animal studies showed that the GDNF-producing progenitor cells can protect motor neurons in the spinal cord, the researchers also recognized that motor neurons within the brain are also involved in ALS. So, for the current study, the team tested the effects of implanting the GDNF-producing cells into the brains of rats with symptoms mimicking an inherited form of ALS.

The team first confirmed that the cells survived, specialized into the right type of brain cells and released GDNF into the brain. More importantly, they went on to show that the transplanted cells not only protected the motor neurons in the brain but also delayed the onset of the disease and extended the survival of the ALS rats.

These results suggest that future clinical trials should test transplantation of the cells into the brain in addition to the spinal cord. The team will first need to carry out more animal studies to determine the cell doses that would be most safe and effective. As first author Gretchen Thomsen, PhD, mentions in a press release, the eventual benefit to patients could be enormous:

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Gretchen Thomsen

“If we are able in the future to reproduce our research results in humans, we could improve both the quality and length of life for patients diagnosed with this devastating disease.”

 

 

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.

Inspiring Video: UC Irvine Stem Cell Trial Gives Orange County Woman Hope in Her Fight Against ALS

Stephen Hawking

Last week, we lost one of our greatest, most influential scientific minds. Stephen Hawking, a famous British theoretical physicist and author of “A Brief History of Time: From the Big Bang to Black Holes”, passed away at the age of 76.

Hawking lived most of his adult life in a wheelchair because he suffered from amyotrophic lateral sclerosis (ALS). Also known as Lou Gehrig’s disease, ALS causes the degeneration of the nerve cells that control muscle movement.

When Hawking was diagnosed with ALS at the age of 21, he was told he only had three years to live. But Hawking defied the odds and went on to live a life that not only revolutionized our understanding of the cosmos, but also gave hope to other patients suffering from this devastating degenerative disease.

A Story of Hope

Speaking of hope, I’d like to share another story of an Orange County woman name Lisa Wittenberg who was recently diagnosed with ALS. Her story was featured this week on KTLA5 news and is also available on the UC Irvine Health website.

VIDEO: UCI Health stem cell trial helps Orange County woman fight neurodegenerative disease ALS. Click on image to view video in new window.

In this video, Lisa describes how quickly ALS changed her life. She was with her family sledding in the snow last winter, and only a year later, she is in a wheelchair unable to walk. Lisa got emotional when she talked about how painful it is for her to see her 13-year-old son watch her battle with this disease.

But there is hope for Lisa in the form of a stem cell clinical trial at the UC Irvine CIRM Alpha Stem Cell Clinic. Lisa enrolled in the Brainstorm study, a CIRM-funded phase 3 trial that’s testing a mesenchymal stem cell therapy called NurOwn. BrainStorm Cell Therapeutics, the company sponsoring this trial, is isolating mesenchymal stem cells from the patient’s own bone marrow. The stem cells are then cultured in the lab under conditions that convert them into biological factories secreting a variety of neurotrophic factors that help protect the nerve cells damaged by ALS. The modified stem cells are then transplanted back into the patient where they will hopefully slow the progression of the disease.

Dr. Namita Goyal, a neurologist at UC Irvine Health involved in the trial, explained in the KTLA5 video that they are hopeful this treatment will give patients more time, and optimistic that in some cases, it could improve some of their symptoms.

Don’t Give Up the Fight

The most powerful part of Lisa’s story to me was the end when she says,

“I think it’s amazing that I get to fight, but I want everybody to get to fight. Everybody with ALS should get to fight and should have hope.”

Not only is Lisa fighting by being in this ground-breaking trial, she is also participated in the Los Angeles marathon this past weekend, raising money for ALS research.

More patients like Lisa will get the chance to fight as more potential stem cell treatments and drugs enter clinical trials. Videos like the one in this blog are important for raising awareness about available clinical trials like the Brainstorm study, which, by the way, is still looking for more patients to enroll (contact information for this trial can be found on the clinicaltrials.gov website here). CIRM is also funding another stem cell trial for ALS at the Cedars-Sinai Medical Center. You can read more about this trial on our website.

Lisa’s powerful message of fighting ALS and having hope reminds me of one of Stephen Hawking’s most famous quotes, which I’ll leave you with:

“Remember to look up at the stars and not down at your feet. Try to make sense of what you see and wonder about what makes the Universe exist. Be curious. And however difficult life may seem, there is always something you can do and succeed at. It matters that you don’t just give up.”


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Stem Cell Roundup: Improving muscle function in muscular dystrophy; Building a better brain; Boosting efficiency in making iPSC’s

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

Photos of the week

TGIF! We’re so excited that the weekend is here that we are sharing not one but TWO amazing stem cell photos of the week.

RMI IntestinalChip

Image caption: Cells of a human intestinal lining, after being placed in an Intestine-Chip, form intestinal folds as they do in the human body. (Photo credit: Cedars-Sinai Board of Governors Regenerative Medicine Institute)

Photo #1 is borrowed from a blog we wrote earlier this week about a new stem cell-based path to personalized medicine. Scientists at Cedars-Sinai are collaborating with a company called Emulate to create intestines-on-a-chip using human stem cells. Their goal is to create 3D-organoids that represent the human gut, grow them on chips, and use these gut-chips to screen for precision medicines that could help patients with intestinal diseases. You can read more about this gut-tastic research here.

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Image caption: UCLA scientists used four different fluorescent-colored proteins to determine the origin of cardiomyocytes in mice. (Image credit: UCLA Broad Stem Cell Research Center/Nature Communications)

Photo #2 is another beautiful fluorescent image, this time of a cross-section of a mouse heart. CIRM-funded scientists from UCLA Broad Stem Cell Research Center are tracking the fate of stem cells in the developing mouse heart in hopes of finding new insights that could lead to stem cell-based therapies for heart attack victims. Their research was published this week in the journal Nature Communications and you can read more about it in a UCLA news release.

Stem cell injection improves muscle function in muscular dystrophy mice

Another study by CIRM-funded Cedars-Sinai scientists came out this week in Stem Cell Reports. They discovered that they could improve muscle function in mice with muscular dystrophy by injecting cardiac progenitor cells into their hearts. The injected cells not only improved heart function in these mice, but also improved muscle function throughout their bodies. The effects were due to the release of microscopic vesicles called exosomes by the injected cells. These cells are currently being used in a CIRM-funded clinical trial by Capricor therapeutics for patients with Duchenne muscular dystrophy.

How to build a better brain (blob)

For years stem cell researchers have been looking for ways to create “mini brains”, to better understand how our own brains work and develop new ways to repair damage. So far, the best they have done is to create blobs, clusters of cells that resemble some parts of the brain. But now researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have come up with a new method they think can advance the field.

Their approach is explained in a fascinating article in the journal Science News, where lead researcher Bennet Novitch says finding the right method is like being a chef:

“It’s like making a cake: You have many different ways in which you can do it. There are all sorts of little tricks that people have come up with to overcome some of the common challenges.”

Brain cake. Yum.

A more efficient way to make iPS cells

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Shinya Yamanaka. (Image source: Ko Sasaki, New York Times)

In 2006 Shinya Yamanaka discovered a way to take ordinary adult cells and reprogram them into embryonic-like stem cells that have the ability to turn into any other cell in the body. He called these cells induced pluripotent stem cells or iPSC’s. Since then researchers have been using these iPSC’s to try and develop new treatments for deadly diseases.

There’s been a big problem, however. Making these cells is really tricky and current methods are really inefficient. Out of a batch of, say, 1,000 cells sometimes only one or two are turned into iPSCs. Obviously, this slows down the pace of research.

Now researchers in Colorado have found a way they say dramatically improves on that. The team says it has to do with controlling the precise levels of reprogramming factors and microRNA and…. Well, you can read how they did it in a news release on Eurekalert.

 

 

 

Stem cell-based gut-on-a-chip: a new path to personalized medicine

“Personalized medicine” is a trendy phrase these days, frequently used in TV ads for hospitals, newspaper articles about medicine’s future and even here in the Stem Cellar. The basic gist is that by analyzing a patient’s unique biology, a physician can use disease treatments that are most likely to work in that individual.

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Emulate’s Organ-on-a-Chip device.
Image: Emulate, Inc.

This concept is pretty straight-forward but it’s not always clear to me how it would play out as a routine clinical service for patients. A recent publication in Cellular and Molecular Gastroenterology and Hepatology by scientists at Cedars-Sinai and Emulate, Inc. paints a clearer picture. The report describes a device, Emulate’s Intestine-Chip, that aims to personalize drug treatments for people suffering from gastrointestinal diseases like inflammatory bowel disease and Chrohn’s disease.

Intestine-Chip combines the cutting-edge technologies of induced pluripotent stem cells (iPSCs) and microfluidic engineering. For the iPSC part of the equation, skin or blood samples are collected from a patient and reprogrammed into stem cells that can mature into almost any cell type in the body. Grown under the right conditions in a lab dish, the iPSCs self-organize into 3D intestinal organoids, structures made up of a few thousand cells with many of the hallmarks of a bona fide intestine.

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Miniature versions of a human intestinal lining, known as organoids, derived from induced pluripotent stem cells (iPSCs).
Image: Cedars-Sinai Board of Governors Regenerative Medicine Institute

These iPSC-derived organoids have been described in previous studies and represent a breakthrough for studying human intestinal diseases. Yet, they vary a lot in shape and size, making it difficult to capture consistent results. And because the intestinal organoids form into hollow tubes, it’s a challenge to get drugs inside the organoid, a necessary step to systematically test the effects of various drugs on the intestine.

The Intestine-Chip remedies these drawbacks. About the size of a double A battery, the Chip is made up of specialized plastic engineered with tiny tunnels, or micro-channels. The research team placed the iPSC-derived intestinal organoid cells into the micro-channels and showed that passing fluids with a defined set of ingredients through the device can prod the cells to mimic the human intestine.

RMI IntestinalChip

Cells of a human intestinal lining, after being placed in an Intestine-Chip, form intestinal folds as they do in the human body. Image: Cedars-Sinai Board of Governors Regenerative Medicine Institute

The Intestine-Chip not only looks like a human intestine but acts like one too. A protein known to be at high levels in inflammatory bowel disease was passed through the microchannel and the impact on the intestinal cells matched what is seen in patients. Clive Svendsen, Ph.D., a co-author on the study and director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute, explained the exciting applications that the Intestine-Chip opens up for patients:

Svendsen

Clive Svendsen

“This pairing of biology and engineering allows us to re-create an intestinal lining that matches that of a patient with a specific intestinal disease—without performing invasive surgery to obtain a tissue sample,” he said in a press release. “We can produce an unlimited number of copies of this tissue and use them to evaluate potential therapies. This is an important advance in personalized medicine.”

Emulate’s sights are not just set on the human intestine but for the many other organs affected by disease. And because disease rarely impacts only one organ, a series of Organs-on-Chips for a particular patient could be examined together. Geraldine A. Hamilton, Ph.D., president and chief scientific officer of Emulate, Inc. summed up this point in a companion press release:

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Geraldine Hamilton

“By creating a personalized Patient-on-a-Chip, we can really begin to understand how diseases, medicines, chemicals and foods affect an individual’s health.”