Rats, research and the road to new therapies

Don Reed

Don Reed has been a champion of CIRM even before there was a CIRM. He’s a pioneer in pushing for funding for stem cell research and now he’s working hard to raise awareness about the difference that funding is making.

In a recent article on Daily Kos, Don highlighted one of the less celebrated partners in this research, the humble rat.

A BETTER RAT? Benefit #62 of the California Stem Cell Agency

By Don C. Reed

When I told my wife Gloria I was writing an article about rats, she had several comments, including: “Oo, ugh!” and also “That’s disgusting!”

Obviously, there are problems with rats, such as when they chew through electrical wires, which may cause a short circuit and burn down the house. Also, they are blamed for carrying diseased fleas in their ears and spreading the Black Plague, which in 1340 killed half of China and one-third of Europe—but this is not certain. The plague may in fact have been transmitted by human-carried parasites.

But there are positive aspects to rats as well. For instance: “…a rat paired with  another that has a disability…will be very kind to the other rat. Usually, help is offered with food, cleaning, and general care.”—GUIDE TO THE RAT, by Ginger Cardinal.

Above all, anyone who has ever been sick owes a debt to rats, specifically the Norway rat with that spectacular name, rattus norvegicus domesticus, found in labs around the world.

I first realized its importance on March 1, 2002, when I held in my hand a rat which had been paralyzed, but then recovered the use of its limbs.

The rat’s name was Fighter, and she had been given a derivative of embryonic stem cells, which restored function to her limbs. (This was the famous stem cell therapy begun by Hans Keirstead with a Roman Reed grant, developed by Geron, and later by CIRM and Asterias, which later benefited humans.)

As I felt the tiny muscles struggling to be free, it was like touching tomorrow— while my paralyzed son, Roman Reed, sat in his wheelchair just a few feet away.

Was it different working with rats instead of mice? I had heard that the far smaller lab mice were more “bitey” than rats.  

Wanting to know more about the possibilities of a “better rat”, I went to the CIRM website, (www.cirm.ca.gov) hunted up the “Tools and Technology III” section, and the following complicated sentence::

“Embryonic stem cell- based generation of rat models for assessing human cellular therapies.”

Hmm. With science writing, it always takes me a couple of readings to know what they were talking about. But I recognized some of the words, so that was a start.

“Stemcells… rat models… human therapies….”  

I called up Dr. Qilong Ying, Principle Investigator (PI) of the study.

As he began to talk, I felt a “click” of recognition, as if, like pieces of a puzzle, facts were fitting together.

It reminded me of Jacques Cousteau, the great underwater explorer, when he tried to invent a way to breathe underwater. He had the compressed air tank, and a mouthpiece that would release air—but it came in a rush, not normal breathing.

So he visited his friend, race car mechanic Emil Gagnan, and told him, “I need something that will give me air, but only when I inhale,”– and Gagnan said: “Like that?” and pointed to a metal contraption on a nearby table.

It was something invented for cars. But by adding it to what Cousteau already had, the Cousteau-Gagnan SCUBA (Self Contained Underwater Breathing Apparatus) gear was born—and the ocean could now be explored.

Qi-Long Ying’s contribution to science may also be a piece of the puzzle of cure…

A long-term collaboration with Dr. Austin Smith centered on an attempt to do with rats what had done with mice.

In 2007, the  Nobel Prize in Medicine had been won by Dr. Martin Evans, Mario Capecchi, and Oliver Smithies. Working independently, they developed “knock-out” and “knock-in” mice, meaning to take out a gene, or put one in.  

But could they do the same with rats?

 “We and others worked very, very hard, and got nowhere,” said Dr. Evans.

Why was this important?

Many human diseases cannot be mimicked in the mouse—but might be in the rat. This is for several reasons: the rat is about ten times larger; its internal workings are closer to those of a human; and the rat is considered several million years closer (in evolutionary terms) to humans than the mouse.

In 2008 (“in China, that is the year of the rat,” noted Dr. Ying in our conversation) he received the first of three grants from CIRM.

“We proposed to use the classical embryonic stem cell-based gene-targeting technology to generate rat models mimicking human heart failure, diabetes and neurodegenerative diseases…”

How did he do?

In 2010, Science Magazine honored him with inclusion in their “Top 10 Breakthroughs for using embryonic stem cell-based gene targeting to produce the world’s first knockout rats, modified to lack one or more genes…”

And in 2016, he and Dr. Smith received the McEwen Award for Innovation,  the highest honor bestowed by the International Society for Stem Cell Research (ISSCR).

Using knowledge learned from the new (and more relevant to humans) lab rat, it may be possible to develop methods for the expansion of stem cells directly inside the patient’s own bone marrow. Stem cells derived in this fashion would be far less likely to be rejected by the patient.  To paraphrase Abraham Lincoln, they would be “of the patient, by the patient and for the patient—and shall not perish from the patient”—sorry!

Several of the rats generated in Ying’s lab (to mimic human diseases) were so successful that they have been donated to the Rat Research Resource center so that other scientists can use them for their study.

“Maybe in the future we will develop a cure for some diseases because of knowledge from using rat models,” said Ying. “I think it’s very possible. So we want more researchers from USC and beyond to come and use this technology.”

And it all began with the humble rat…

Stem Cell Agency Invests in New Immunotherapy Approach to HIV, Plus Promising Projects Targeting Blindness and Leukemia

HIV AIDS

While we have made great progress in developing therapies that control the AIDS virus, HIV/AIDS remains a chronic condition and HIV medicines themselves can give rise to a new set of medical issues. That’s why the Board of the California Institute for Regenerative Medicine (CIRM) has awarded $3.8 million to a team from City of Hope to develop an HIV immunotherapy.

The City of Hope team, led by Xiuli Wang, is developing a chimeric antigen receptor T cell or CAR-T that will enable them to target and kill HIV Infection. These CAR-T cells are designed to respond to a vaccine to expand on demand to battle residual HIV as required.

Jeff Sheehy

CIRM Board member Jeff Sheehy

Jeff Sheehy, a CIRM Board member and patient advocate for HIV/AIDS, says there is a real need for a new approach.

“With 37 million people worldwide living with HIV, including one million Americans, a single treatment that cures is desperately needed.  An exciting feature of this approach is the way it is combined with the cytomegalovirus (CMV) vaccine. Making CAR T therapies safer and more efficient would not only help produce a new HIV treatment but would help with CAR T cancer therapies and could facilitate CAR T therapies for other diseases.”

This is a late stage pre-clinical program with a goal of developing the cell therapy and getting the data needed to apply to the Food and Drug Administration (FDA) for permission to start a clinical trial.

The Board also approved three projects under its Translation Research Program, this is promising research that is building on basic scientific studies to hopefully create new therapies.

  • $5.068 million to University of California at Los Angeles’ Steven Schwartz to use a patient’s own adult cells to develop a treatment for diseases of the retina that can lead to blindness
  • $4.17 million to Karin Gaensler at the University of California at San Francisco to use a leukemia patient’s own cells to develop a vaccine that will stimulate their immune system to attack and destroy leukemia stem cells
  • Almost $4.24 million to Stanford’s Ted Leng to develop an off-the-shelf treatment for age-related macular degeneration (AMD), the leading cause of vision loss in the elderly.

The Board also approved funding for seven projects in the Discovery Quest Program. The Quest program promotes the discovery of promising new stem cell-based technologies that will be ready to move to the next level, the translational category, within two years, with an ultimate goal of improving patient care.

Application Title Institution CIRM Committed Funding
DISC2-10979 Universal Pluripotent Liver Failure Therapy (UPLiFT)

 

Children’s Hospital of Los Angeles $1,297,512

 

DISC2-11105 Pluripotent stem cell-derived bladder epithelial progenitors for definitive cell replacement therapy of bladder cancer

 

Stanford $1,415,016
DISC2-10973 Small Molecule Proteostasis Regulators to Treat Photoreceptor Diseases

 

U.C. San Diego $1,160,648
DISC2-11070 Drug Development for Autism Spectrum Disorder Using Human Patient iPSCs

 

Scripps $1,827,576
DISC2-11183 A screen for drugs to protect against chemotherapy-induced hearing loss, using sensory hair cells derived by direct lineage reprogramming from hiPSCs

 

University of Southern California $833,971
DISC2-11199 Modulation of the Wnt pathway to restore inner ear function

 

Stanford $1,394,870
DISC2-11109 Regenerative Thymic Tissues as Curative Cell Therapy for Patients with 22q11 Deletion Syndrome

 

Stanford $1,415,016

Finally, the Board approved the Agency’s 2019 research budget. Given CIRM’s new partnership with the National Heart, Lung, Blood Institute (NHLBI) to accelerate promising therapies that could help people with Sickle Cell Disease (SCD) the Agency is proposing to set aside $30 million in funding for this program.

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Congresswoman Barbara Lee (D-CA 13th District)

“I am deeply grateful for organizations like CIRM and NHLBI that do vital work every day to help people struggling with Sickle Cell Disease,” said Congresswoman Barbara Lee (D-CA 13th District). “As a member of the House Appropriations Subcommittee on Labor, Health and Human Services, and Education, I know well the importance of this work. This innovative partnership between CIRM and NHLBI is an encouraging sign of progress, and I applaud both organizations for their tireless work to cure Sickle Cell Disease.”

Under the agreement CIRM and the NHLBI will coordinate efforts to identify and co-fund promising therapies targeting SCD.  Programs that are ready to start an IND-enabling or clinical trial project for sickle cell can apply to CIRM for funding from both agencies. CIRM will share application information with the NHLBI and CIRM’s Grants Working Group (GWG) – an independent panel of experts which reviews the scientific merits of applications – will review the applications and make recommendations. The NHLBI will then quickly decide if it wants to partner with CIRM on co-funding the project and if the CIRM governing Board approves the project for funding, the two organizations will agree on a cost-sharing partnership for the clinical trial. CIRM will then set the milestones and manage the single CIRM award and all monitoring of the project.

“This is an extraordinary opportunity to create a first-of-its-kind partnership with the NHLBI to accelerate the development of curative cell and gene treatments for patients suffering with Sickle Cell Disease” says Maria T. Millan, MD, President & CEO of CIRM. “This allows us to multiply the impact each dollar has to find relief for children and adults who battle with this life-threatening, disabling condition that results in a dramatically shortened lifespan.  We are pleased to be able to leverage CIRM’s acceleration model, expertise and infrastructure to partner with the NHLBI to find a cure for this condition that afflicts 100,000 Americans and millions around the globe.”

The budget for 2019 is:

Program type 2019
CLIN1 & 2

CLIN1& 2 Sickle Cell Disease

$93 million

$30 million

TRANSLATIONAL $20 million
DISCOVER $0
EDUCATION $600K

 

 

Hits and Myths as people celebrate Stem Cell Awareness Day

UC Davis #1

Stem Cell Awareness Day at UC Davis

Every year, the second Wednesday in October is set aside as Stem Cell Awareness Day, a time to celebrate the progress being made in the field and to remind us of the challenges that lie ahead.

While the event began here in California in 2008, with then-Governor Arnold Schwarzenegger highlighting the work of CIRM, saying: ”The discoveries being made today in our Golden State will have a great impact on many around the world for generations to come.” It has since grown to become a global event.

Here in California, for example, UC Davis and the University of Southern California (USC) both held events to mark the day.

At UC Davis Jan Nolta, PhD., the Director of the Stem Cell Program, introduced a series of speakers who highlighted the terrific work being done at the university. Peter Belafsky talked about using stem cells to repair damaged trachea and to help people who are experiencing voice or swallowing disorders. Mark Lee highlighted the progress being made in using stem cells to repair hard-to-heal broken bones. Aijun Wang focused on some really exciting work that could one day lead to a therapy for spina bifida (including some ridiculously cute video of English bulldogs who are able to walk again because of this therapy.)

USC hosted 100 local high school students for a panel presentation and discussion about careers in stem cell research. The panel featured four scientists talking about their experience, why the students should think about a career in science and how to go about planning one. USC put together a terrific video of the researchers talking about their experiences, something that can help any student around the US consider becoming part of the future of stem cell research.

Similar events were held in other institutions around California. But the celebration wasn’t limited to the Golden State. At the Texas Heart Institute in Houston, Texas, they held an event to talk to the public about the clinical trials they are supporting using stem cells to help people suffering from heart failure or other heart-related issues.

RegMedNet

Finally, the UK-based RegMedNet, a community site that unites the diverse regenerative medicine community, marked the day by exploring some of the myths and misconceptions still surrounding stem cells and stem cell research.

You can read those here.

Every group takes a different approach to celebrating Stem Cell Awareness Day, but each is united by a common desire, to help people understand the progress being made in finding new treatments and even cures for people with unmet medical needs.

Timing is a critical factor in kidney development

Through countless studies, it’s clear that genes and environmental factors are important for determining cellular identity. Now, a research team at the University of Southern California  (USC) have found that timing is another critical factor in determining cell fate during organ development.

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Developing human nephron, the filtering unit of the kidney. Image by Nils O. Lindstrom and Tracy Tran/McMahon Lab USC Stem Cell

In findings published in Development Cell, Dr. Andy McMahon’s group shows that development of the nephron, the filtering structure of the kidney, is acutely dependent on when cells arrive in that developmental region. Cells that arrive in the developing nephron early become part of the tubule, which is responsible for reabsorption of water and salt, whereas cells that arrive late become part of the glomerulus, the structure that is responsible for filtering blood.

The scientists verified that timing influenced cell identity with a combination of microscopy, which allowed them to follow particular cell types as they developed, and single-cell RNA sequencing, which allowed them to determine how gene expression changes in a population of cells.

In a press release, Dr. McMahon details the importance of these findings:

“By studying normal human nephron development, we’re gaining important information about how to replicate this intricate process in the laboratory. The hope is that laboratory-grown nephrons can be used to further study the process of development, screen potential therapies to treat disease, and eventually provide the building blocks to assemble functional kidneys for transplantation into patients.”

Understanding kidney development is crucial because approximately 30 million people suffer from chronic kidney disease and it is the ninth leading cause of death in the United States alone. Insights into the basics of kidney biology can provide important advances to develop novel therapeutics for this devastating condition.

Friday Stem Cell Round: Ask the Expert Facebook Live, Old Brain Cells Reveal Insights and Synthetic Development

Stem Cell Photo of the Week: We’re Live on Facebook Live!

Our stem cell photo of the week is a screenshot from yesterday’s Facebook Live event: “Ask the Expert: Stem Cells and Stroke”. It was our first foray into Facebook Live and, dare I say, it was a success with over 150 comments and 4,500 views during the live broadcast.

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Screen shot of yesterday’s Facebook Live event. Panelists included (from top left going clockwise): Sonia Coontz, Kevin McCormack, Gary Steinberg, MD, PhD and Lila Collins, PhD.

Our panel included Dr. Gary Steinberg, MD, PhD, the Chair of Neurosurgery at Stanford University, who talked about promising clinical trial results testing a stem cell-based treatment for stroke. Lila Collins, PhD, a Senior Science Officer here at CIRM, provided a big picture overview of the latest progress in stem cell therapies for stroke. Sonia Coontz, a patient of Dr. Steinberg’s, also joined the live broadcast. She suffered a devastating stroke several years ago and made a remarkable recovery after getting a stem cell therapy. She had an amazing story to tell. And Kevin McCormack, CIRM’s Senior Director of Public Communications, moderated the discussion.

Did you miss the Facebook Live event? Not to worry. You can watch it on-demand on our Facebook Page.

What other disease areas would you like us to discuss? We plan to have these Ask the Expert shows on a regular basis so let us know by commenting here or emailing us at info@cirm.ca.gov!

Brain cells’ energy “factories” may be to blame for age-related disease

Salk Institute researchers published results this week that shed new light on why the brains of older individuals may be more prone to neurodegenerative diseases like Parkinson’s and Alzheimer’s. To make this discovery, the team applied a technique they devised back in 2015 which directly converts skin cells into brain cells, aka neurons. The method skips the typical intermediate step of reprogramming the skin cells into induced pluripotent stem cells (iPSCs).

They collected skin samples from people ranging in age from 0 to 89 and generated neurons from each. With these cells in hand, the researchers then examined how increased age affects the neurons’ mitochondria, the structures responsible for producing a cell’s energy needs. Previous studies have shown a connection between faulty mitochondria and age-related disease.

While the age of the skin cells had no bearing on the health of the mitochondria, it was a different story once they were converted into neurons. The mitochondria in neurons derived from older individuals clearly showed signs of deterioration and produced less energy.

Aged-mitochondria-green-in-old-neurons-gray-appear-mostly-as-small-punctate-dots-rather-than-a-large-interconnected-network-300x301

Aged mitochondria (green) in old neurons (gray) appear mostly as small punctate dots rather than a large interconnected network. Credit: Salk Institute.

The researchers think this stark difference in the impact of age on skin cells vs. neurons may occur because neurons have higher energy needs. So, the effects of old age on mitochondria only become apparent in the neurons. In a press release, Salk scientist Jerome Mertens explained the result using a great analogy:

“If you have an old car with a bad engine that sits in your garage every day, it doesn’t matter. But if you’re commuting with that car, the engine becomes a big problem.”

The team is now eager to use this method to examine mitochondrial function in neurons derived from Alzheimer’s and Parkinson’s patient skin samples and compared them with skin-derived neurons from similarly-aged, healthy individuals.

The study, funded in part by CIRM, was published in Cell Reports.

“Synthetically” Programming embryo development

One of the most intriguing, most fundamental questions in biology is how an embryo, basically a non-descript ball of cells, turns into a complex animal with eyes, a brain, a heart, etc. A deep understanding of this process will help researchers who aim to rebuild damaged or diseased organs for patients in need.

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Researchers programmed cells to self-assemble into complex structures such as this one with three differently colored layers. Credit: Wendell Lim/UCSF

A fascinating report published this week describes a system that allows researchers to program cells to self-organize into three-dimensional structures that mimic those seen during early development. The study applied a customizable, synthetic signaling molecule called synNotch developed in the Wendell Lim’s UCSF lab by co-author Kole Roybal, PhD, now an assistant professor of microbiology and immunology at UCSF, and Leonardo Morsut, PhD, now an assistant professor of stem cell biology and regenerative medicine at the University of Southern California.

A UCSF press release by Nick Weiler describes how synNotch was used:

“The researchers engineered cells to respond to specific signals from neighboring cells by producing Velcro-like adhesion molecules called cadherins as well as fluorescent marker proteins. Remarkably, just a few simple forms of collective cell communication were sufficient to cause ensembles of cells to change color and self-organize into multi-layered structures akin to simple organisms or developing tissues.”

Senior author Wendell Lim also explained how this system could overcome the challenges facing those aiming to build organs via 3D bioprinting technologies:

“People talk about 3D-printing organs, but that is really quite different from how biology builds tissues. Imagine if you had to build a human by meticulously placing every cell just where it needs to be and gluing it in place. It’s equally hard to imagine how you would print a complete organ, then make sure it was hooked up properly to the bloodstream and the rest of the body. The beauty of self-organizing systems is that they are autonomous and compactly encoded. You put in one or a few cells, and they grow and organize, taking care of the microscopic details themselves.”

Study was published in Science.

Stem Cell Roundup: Protein shows promise in treating deadliest form of breast cancer: mosquito spit primes our body for disease

Triple negative breast cancerTriple negative breast cancer is more aggressive and difficult to treat than other forms of the disease and, as a result, is more likely to spread throughout the body and to recur after treatment. Now a team at the University of Southern California have identified a protein that could help change that.

The research, published in the journal Nature Communications, showed that a protein called TAK1 allows cancer cells from the tumor to migrate to the lungs and then form new tumors which can spread throughout the body. There is already an FDA-approved drug called OXO that has been shown to block TAK1, but this does not survive in the blood so it’s hard to deliver to the lungs.

The USC team found a way of using nanoparticles, essentially a tiny delivery system, to take OXO and carry it to the lungs to attack the cancer cells and stop them spreading.

triple_negative_breast_cancer_particle_graphic-768x651In a news release Min Yu, the principal investigator on the team, said that although this has only been tested in mice the results are encouraging:

“For patients with triple-negative breast cancer, systemic chemotherapies are largely ineffective and highly toxic. So, nanoparticles are a promising approach for delivering more targeted treatments, such as OXO, to stop the deadly process of metastasis.”

Mosquito spit and your immune system

Mosquito

Mosquito bite: Photo courtesy National Academy of Sciences

Anyone who has ever been bitten by a mosquito knows that it can be itchy and irritable for hours afterwards. But now scientists say the impact of that bite can last for much longer, days in fact, and even help prime your body for disease.

The scientists say that every time a mosquito bites you they inject saliva into the bite to keep the blood flowing freely. But that saliva also has an impact on your immune system, leaving it more vulnerable to diseases like malaria.

OK, so that’s fascinating, and really quite disgusting, but what does it have to do with stem cells? Well, researchers at the National Institute of Health’s (NIH) Malaria and Vector Research Laboratory in Phnom Penh, Cambodia engrafted human stem cells into mice to study the problem.

They found that mice with the human stem cells developed more severe symptoms of dengue fever if they were bitten by a mosquito than if they were just injected with dengue fever.

In an article in Popular Science Jessica Manning, an infectious disease expert at the NIH, said previously we had no idea that mosquito spit had such a big impact on us:

“The virus present in that mosquito’s saliva, it’s like a Trojan horse. Your body is distracted by the saliva [and] having an allergic reaction when really it should be having an antiviral reaction and fighting against the virus. Your body is unwittingly helping the virus establish infection because your immune system is sending in new waves of cells that this virus is able to infect.”

The good news is that if we can develop a vaccine against the saliva we may be able to protect people against malaria, dengue fever, Zika and other mosquito-borne diseases.

The moment of truth. A video about the stem cell therapy that could help millions of people going blind.

“No matter how much one prepares, the first patient is always something very special.” That’s how Dr. Mark Humayun describes his feelings as he prepared to deliver a CIRM-funded stem cell therapy to help someone going blind from dry age-related macular degeneration (AMD).

Humayun, an ophthalmologist and stem cell researcher at USC, spent years developing this therapy and so it’s understandable that he might be a little nervous finally getting a chance to see if it works in people.

It’s quite a complicated procedure, involving turning embryonic stem cells into the kind of cells that are destroyed by AMD, placing those cells onto a specially developed synthetic scaffold and then surgically implanting the cells and scaffold onto the back of the eye.

There’s a real need for a treatment for AMD, the leading cause of vision loss in the US. Right now, there is no effective therapy for AMD and some three million Americans are facing the prospect of losing their eyesight.

The first, preliminary, results of this trial were released last week and they were encouraging. You can read about them on our blog.

Thanks to USC you can also see the team that developed and executed this promising approach. They created a video capturing the moment the team were finally taking all that hard work and delivering it where it matters, to the patient.

Watching the video it’s hard not to think you are watching a piece of history, something that has the potential to do more than just offer hope to people losing their vision, it has the potential to stop and even reverse that process.

The video is a salute to the researchers who developed the therapy, and the doctors, nurses and Operating Room team who delivered it. It’s also a salute to the person lying down, the patient who volunteered to be the first to try this. Everyone in that room is a pioneer.

Encouraging news about CIRM-funded clinical trial targeting vision loss

dry AMD

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.

 

 

A shot in the arm for people with bad knees

knee

Almost every day I get an email or phone call from someone asking if we have a stem cell therapy for bad knees. The inquiries are from people who’ve been told they need surgery to replace joints damaged by age and arthritis. They’re not alone. Every year around 600,000 Americans get a knee replacement. That number is expected to rise to three million by 2030.

Up till now my answer to those calls and emails has been ‘I’m sorry, we don’t have anything’. But a new CIRM-funded study from USC stem cell scientist Denis Evseenko says that may not always be the case.

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The ability to regenerate joint cartilage cells instead of surgically replacing joints would be a big boon for future patients. (Photo/Nancy Liu, Denis Evseenko Lab, USC Stem Cell)

Evseenko and his team have discovered a molecule they have called Regulator of Cartilage Growth and Differentiation or RCGD 423. This cunning molecule works in two different ways. One is to reduce the inflammation that many people with arthritis have in their joints. The second is to help stimulate the regeneration of the cartilage destroyed by arthritis.

When they tested RCGD 423 in rats with damaged cartilage, the rats cartilage improved. The study is published in the Annals of Rheumatic Diseases.

In an article in USC News, Evseenko, says there is a lot of work to do but that this approach could ultimately help people with osteoarthritis or juvenile arthritis.

“The goal is to make an injectable therapy for an early to moderate level of arthritis. It’s not going to cure arthritis, but it will delay the progression of arthritis to the damaging stages when patients need joint replacements, which account for a million surgeries a year in the U.S.”

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.”