Stem Cell Roundup: Battle of the Biotech Bands, “Cells I See” Art Contest and Teaching Baseball Fans the Power of Stem Cells

This Friday’s stem cell roundup is dedicated to the playful side of stem cell science. Scientists are often stereotyped as lab recluses who honorably forgo social lives in the quest to make game-changing discoveries and advance cutting-edge research. But as a former bench scientist, I can attest that scientists are normal people too. They might have a nerdy, slightly neurotic side around their field of research, but they know how to enjoy life and have fun. So here are a few stories that caught our eye this week about scientists having a good time with science.

Rockin’ researchers battle for glory (Kevin McCormack)

Did you know that Bruce Springsteen got his big break after winning the Biotech Battle of the Bands (BBOB)? Probably not, I just made that up. But just because Bruce didn’t hit it big because of BBOB doesn’t mean you can’t.

BBOB is a fun chance for you and your labmates, or research partners, to cast off your lab coats, pick up a guitar, form a band, show off your musical chops, play before a live audience and raise money for charity.  This is the fourth year the event is being held. It’s part of Biotech Week Boston, on Wednesday, September 27th at the Royale Nightclub, Boston.

Biotech Week is a celebration of science and, duh, biotech; bringing together what the event organizers call “the most inventive scientific minds and business leaders in Boston and around the world.” And they wouldn’t lie would they, after all, they’re scientists.

If you want to check out the competition here’s some video from a previous year – see if you can spot the man with the cowbell!

“Cells I See” Stem Cell Art Contest

It’s that time again! The “Cells I See” art contest hosted by Canada’s Centre for Commercialization for Regenerative Medicine (CCRM) and The Stem Cell Network is now open for business. This is a super fun event that celebrates the beauty of stem cells and biomaterials that support regenerative medicine.

Not only is “Cells I See” a great way for scientists to share their research with the public, it’s also a way for them to tap into their artistic, creative side. Last year’s ­contestants submitted breathtaking microscope images, paintings and graphic designs of stem cells in action. The titles for these art submissions were playful. “Nucleic Shower” “The Quest for Innervation” and “Flat, Fluorescent & Fabulous” were some of my favorite title entries.

There are two prizes for this contest. The grand prize of $750 will be awarded to the submission with the highest number of votes from scientists attending the Till and McCulloch Stem Cell Meeting in November. There is also a “People’s Choice” prize of $500 given to the contestant who has the most numbers of likes on the CCRM Facebook page.

The deadline for “Cell I See” submissions is September 8th so you have plenty of time to get your creative juices flowing!

Iris

The 2016 Grand Prize and People’s Choice Winner, Sabiha Hacibekiroglu, won for her photo titled “Iris”.

Scientists Teach Baseball Fans the Power of Stem Cells

San Francisco Giants fans who attended Tuesday’s ball game were in for a special treat – a science treat that is. Researchers from the Gladstone Institutes partnered with the SF Giants to raise awareness about the power of stem cells for advancing research and developing cures for various diseases.

Gladstone PhD student Jessica Butts explains the Stem Cell Plinko game to a Giants fan.

The Gladstone team had a snazzy stem cell booth at the Giant’s Community Clubhouse with fun science swag and educational stem cell activities for fans of all ages. One of the activities was a game called “Stem Cell Plinko” where you drop a ball representing a pluripotent stem cell down a plinko board. The path the ball travels represents how that stem cell differentiates or matures into adult cells like those in the heart.

Gladstone also debuted their new animated stem cell video, which explains how “stem cell research has opened up promising avenues for personalized and regenerative medicine.”

Finally, Gladstone scientists challenged fans to participate in a social media contest about their newfound stem cell knowledge cells on Twitter. The winner of the contest, a woman named Nicole, will get an exclusive, behind-the-scenes lab tour at the Gladstone and “see firsthand how Gladstone is using stem cells to overcome disease.”

The Gladstone “Power of Stem Cells” event is a great example of how scientists are trying to make research and science more accessible to the public. It not only benefits people by educating them about the current state of stem cell research, but also is a fun way for scientists to engage with the local community.

“Participating in the SF Giants game was very fun,” said Megan McDevitt, vice president of communications at the Gladstone Institutes. “Our booth experienced heavy traffic all evening, giving us a wonderful opportunity to engage with the San Francisco community about science and, more specifically, stem cell research. We were delighted to see how interested fans were to learn more on the topic.”

And as if all that wasn’t enough, the Giants won, something that hasn’t been happening very much this season.

Go Giants. Go Gladstone.

Gladstone scientist dropping stem cell knowledge to Giants fans.

Stem cell agency funds Phase 3 clinical trial for Lou Gehrig’s disease

ALS

At CIRM we don’t have a disease hierarchy list that we use to guide where our funding goes. We don’t rank a disease by how many people suffer from it, if it affects children or adults, or how painful it is. But if we did have that kind of hierarchy you can be sure that Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, would be high on that list.

ALS is a truly nasty disease. It attacks the neurons, the cells in our brain and spinal cord that tell our muscles what to do. As those cells are destroyed we lose our ability to walk, to swallow, to talk, and ultimately to breathe.

As Dr. Maria Millan, CIRM’s interim President and CEO, said in a news release, it’s a fast-moving disease:

“ALS is a devastating disease with an average life expectancy of less than five years, and individuals afflicted with this condition suffer an extreme loss in quality of life. CIRM’s mission is to accelerate stem cell treatments to patients with unmet medical needs and, in keeping with this mission, our objective is to find a treatment for patients ravaged by this neurological condition for which there is currently no cure.”

Having given several talks to ALS support groups around the state, I have had the privilege of meeting many people with ALS and their families. I have seen how quickly the disease works and the devastation it brings. I’m always left in awe by the courage and dignity with which people bear it.

BrainStorm

I thought of those people, those families, today, when our governing Board voted to invest $15.9 million in a Phase 3 clinical trial for ALS run by BrainStorm Cell Therapeutics. BrainStorm is using mesenchymal stem cells (MSCs) that are taken from the patient’s own bone marrow. This reduces the risk of the patient’s immune system fighting the therapy.

After being removed, the MSCs are then modified in the laboratory to  boost their production of neurotrophic factors, proteins which are known to help support and protect the cells destroyed by ALS. The therapy, called NurOwn, is then re-infused back into the patient.

In an earlier Phase 2 clinical trial, NurOwn showed that it was safe and well tolerated by patients. It also showed evidence that it can help stop, or even reverse  the progression of the disease over a six month period, compared to a placebo.

CIRM is already funding one clinical trial program focused on treating ALS – that’s the work of Dr. Clive Svendsen and his team at Cedars Sinai, you can read about that here. Being able to add a second project, one that is in a Phase 3 clinical trial – the last stage before, hopefully, getting approval from the Food and Drug Administration (FDA) for wider use – means we are one step closer to being able to offer people with ALS a treatment that can help them.

Diane Winokur, the CIRM Board Patient Advocate member for ALS, says this is something that has been a long time coming:

CIRM Board member and ALS Patient Advocate Diane Winokur

“I lost two sons to ALS.  When my youngest son was diagnosed, he was confident that I would find something to save him.  There was very little research being done for ALS and most of that was very limited in scope.  There was one drug that had been developed.  It was being released for compassionate use and was scheduled to be reviewed by the FDA in the near future.  I was able to get the drug for Douglas.  It didn’t really help him and it was ultimately not approved by the FDA.

When my older son was diagnosed five years later, he too was convinced I would find a therapy.  Again, I talked to everyone in the field, searched every related study, but could find nothing promising.

I am tenacious by nature, and after Hugh’s death, though tempted to give up, I renewed my search.  There were more people, labs, companies looking at neurodegenerative diseases.

These two trials that CIRM is now funding represent breakthrough moments for me and for everyone touched by ALS.  I feel that they are a promising beginning.  I wish it had happened sooner.  In a way, though, they have validated Douglas and Hugh’s faith in me.”

These therapies are not a cure for ALS. At least not yet. But what they will do is hopefully help buy people time, and give them a sense of hope. For a disease that leaves people desperately short of both time and hope, that would be a precious gift. And for people like Diane Winokur, who have fought so hard to find something to help their loved ones, it’s a vindication that those efforts have not been in vain.

Bridging the divide: stem cell students helping families with rare diseases become partners in research

Bridges & Rare Science

CIRM’s Bridges students and Rare Science’s families with rare diseases

Sometimes it’s the simplest things that make the biggest impact. For example, introducing a scientist to a patient can help them drive stem cell research forward faster than either one could do on their own.

Want proof? This year, students in CIRM’s Bridges to Stem Cell Research and Therapy program at California State University (CSU) San Marcos teamed up with parents of children with rare diseases, and the partnerships had a profound impact on all of them, one we hope might produce some long-term benefits.

Christina Waters, who helped create the partnerships, calls it “science with love.”

“We wanted to change the conversation and have researchers and families communicate, making families equal stakeholders in the research. The students bonded with the families and I truly feel that we made a difference in the lives of future researchers, in knowing how much their work can make a life changing impact on the lives of patients’ families who now have hope.”

The CIRM Bridges program helps prepare California’s undergraduate and master’s graduate students for highly productive careers in stem cell research. Students get a paid internship where they get hands-on training and education in stem cell research. They also work with patients and take part in outreach activities so they get an understanding of research that extends beyond the lab.

That’s where Christina Waters comes in. Christina is the founder of Rare Science, a non-profit group focused on rare diseases in children – we blogged about her work here – and she teamed up with CSU San Marcos to partner their Bridges students with five patient families with different rare diseases.

Cutting edge science

One of those families was Aaron Harding’s. Aaron’s son Jaxon has SYNGAP, a genetic disorder that can cause seizures, mental retardation, speech problems and autistic-like behavior. Two of the Bridges students who were doing their internship at ThermoFisher Scientific, Uju Nwizu and Emily Asbury, were given the task of using the gene-editing tool CRISPR Cas9 to help develop a deeper understanding of SYNGAP.

The students say it was an amazing experience:

Uju: “It had a huge impact on me. Every time I thought about SYNGAP I saw Jaxon’s face. This motivated me a lot.”

Emily: “People who work in labs everyday are most often working out the minutiae of research. They don’t often get a chance to see how their research can change or save the lives of real people. Meeting patients is so motivating because afterwards you aren’t just studying a mechanism, you now have a friend with the disease, so you can’t help but be personally invested in the search for a treatment.”

Emily and Uju are working to create iPSCs (induced pluripotent stem cells) that have the SYNGAP mutation. They hope these can be used to study the disease in greater depth and, maybe one day, lead to treatments for some of the symptoms.

Aaron says for families like his, knowing there are scientists working on his child’s disorder is a source of comfort, and hope:

“Personalizing diseases by connecting scientists with those they seek to impact is so important. Emily and Uju took this opportunity and ran with it, and that says a lot about them, and the team at ThermoFisher, taking on an exploring the unknown. That attitude is the heart of a scientist.”

Hearing stories like this is very gratifying, not just for the students and families involved, but for everyone here at CIRM. When we created the Bridges program our goal was to help students get the skills and experience needed to pursue a career in science. Thanks to the people at CSU San Marcos and Rare Science these students got a whole lot more.

Christina Waters: “We learned, we shared hope, we celebrated the courage of our families and the commitment of the students. It takes a village, and it is all of us working together that will make great changes for kids with rare diseases.”

For Uju and Emily, their experience in the Bridges program has made them doubly certain they want to pursue a career in science.

Uju: “I love stem cells and the promise they hold. After this program I hope to be part of a team that is committed to accelerating new stem cell therapies for rare and chronic diseases.”

Emily: “I’ve learned that I love research. After I finish my bachelor’s degree at CSU San Marcos I plan to pursue a graduate degree in molecular or cellular biology.”

 

Humacyte Receives Prestigious Technology Pioneer Award for Kidney Failure Treatment

This month, a CIRM-funded company called Humacyte was named one of the World Economic Forum’s 30 Technology Pioneers for 2017. This prestigious award “recognizes early-stage companies from around the world that are involved in the design, development and deployment of new technologies and innovations, and are poised to have a significant impact on business and society.”

Humacyte is a North Carolina-based company that’s developing a promising human-tissue based treatment for kidney failure. They’ve developed a technology to manufacture a bioengineered human vein that they hope will improve kidney function in patients with end stage kidney disease and patients on hemodialysis. We’ve blogged about their exciting technology previously on the Stem Cellar (here).

The technology is fascinating. The first step involves stimulating human smooth muscle cells from donor tissue to develop into tubular vessels. After the vessels are made, the cells are removed, leaving a 3D extracellular matrix structure composed of molecules secreted by the cells. This decellularized tube-like structure is called a human acellular vessels or HAV.

Human acellular vessel (HAV) from Humacyte.

The HAV is then implanted under a patient’s skin, where it recruits the patient’s own stem cells to migrate into the HAV and develop into vascular smooth muscle cells that line the insides of actual blood vessels. For patients with kidney failure, HAVs provide vascular access for hemodialysis, the process of collecting and filtering a patient’s blood through an artificial kidney and then returning “clean” blood back to the body. It would provide an alternative to the current procedures that insert a plastic tube called a shunt into the patient’s vein. Shunts can cause infection, blood clots, and can also be rejected by a patient’s immune system.

In July of 2016, CIRM awarded Humacyte almost $10 million to launch a Phase 3 trial in California to test their bioengineered blood vessels in patients with kidney failure. Since launching the trial, Humacyte received Regenerative Medicine Advanced Therapy or RMAT designation from the US Food and Drug Administration in March of this year. This designation is a sign that the FDA sees promise in Humacyte’s stem cell-based therapy and “will help facilitate the efficient development and expedited review of the HAV for vascular access to patients in need of life-sustaining hemodialysis.”

Humacyte’s technology has wide-ranging applications beyond treating kidney disease, including peripheral arterial disease, “repairing or replacing damaged arteries, coronary artery bypass surgery, and vascular trauma.” Other key benefits of this technology are that HAVs can be designed on demand and can be stored for later use without fear of a rapidly degrading shelf-life.

In a recent Humacyte news release, Carrie Cox, Chair and CEO of Humacyte, commented on her company’s purpose and vision to help patients.

“Keeping patient care at its core, Humacyte’s scientific discoveries are designed to create ‘off-the-shelf,’ or ready to use, bioengineered blood vessels. Today these conduits are being investigated clinically for patients undergoing kidney dialysis who require vascular access and for patients with peripheral arterial disease. However, this technology may be extended into a range of vascular applications in the future, with the potential for better clinical outcomes and lower healthcare costs. Our vision is to make a meaningful impact in healthcare by advancing innovation in regenerative medicine to produce life-sustaining improvements for patients with vascular disease.”

The potential impact that Humacyte’s technology could have for patients with unmet medical needs was compelling enough to earn the company a coveted spot in the World Economic Forum’s Technology Pioneer community. This recognition will likely foster new partnerships and collaborations to further advance Humacyte’s technology down the clinical pipeline. Fulvia Montresor, Head of Technology Pioneers at the World Economic Forum, concluded in a news release.

“We welcome Humacyte in this group of extraordinary pioneers. We hope that thanks to this selection, the World Economic Forum can facilitate greater collaboration with business leaders, governments, civil society and other relevant individuals to accelerate the development of technological solutions to the world’s greatest challenges.”

According to coverage by North Carolina Biotechnology Center, Humacyte and the other Technology Pioneers will be honored at the “Summer Davos” World Economic Forum Annual Meeting of the New Champions later this month in China. You can learn more about this meeting here.


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Have scientists discovered a natural way to boost muscle regeneration?

Painkillers like ibuprofen and aspirin are often a part of an athlete’s post-exercise regimen after intense workouts. Sore muscles, aches and stiffness can be more manageable by taking these drugs – collectively called non-steroidal anti-inflammatory drugs, or NSAIDS – to reduce inflammation and pain. But research suggests that the anti-inflammatory effects of these painkillers might cause more harm than good by preventing muscle repair and regeneration after injury or exercise.

A new study out of Stanford Medicine supports these findings and proposes that a component of the inflammatory process is necessary to promote muscle regeneration. Their study was funded in part by a CIRM grant and was published this week in the Proceedings of the National Academy of Sciences.

Muscle stem cells are scattered throughout skeletal muscle tissue and remain inactive until they are stimulated to divide. When muscles are damaged or injured, an inflammatory response involving a cascade of immune cells, molecules and growth factors activates these stem cells, prompting them to regenerate muscle tissue.

Andrew Ho, Helen Blau and Adelaida Palla led a study that found drugs like aspirin and ibuprofen can inhibit the ability of muscle tissue to repair itself in mice. (Image credit: Scott Reiff)

The Stanford team discovered that a molecule called Prostaglandin E2 or PGE2 is released during the inflammatory response and stimulates muscle repair by directly targeting the EP4 receptor on the surface of muscle stem cells. The interaction between PGE2 and EP4 causes muscle stem cells to divide and robustly regenerate muscle tissue.

Senior author on the study, Dr. Helen Blau, explained her team’s interest in PGE2-mediated muscle repair in a news release,

“Traditionally, inflammation has been considered a natural, but sometimes harmful, response to injury. But we wondered whether there might be a component in the pro-inflammatory signaling cascade that also stimulated muscle repair. We found that a single exposure to prostaglandin E2 has a profound effect on the proliferation of muscle stem cells in living animals. We postulated that we could enhance muscle regeneration by simply augmenting this natural physiological process in existing stem cells already located along the muscle fiber.”

Further studies in mice revealed that injury increased PGE2 levels in muscle tissue and increased expression of the EP4 receptor on muscle stem cells. This gave the authors the idea that treating mice with a pulse of PGE2 could stimulate their muscle stem cells to regenerate muscle tissue.

Their hunch turned out to be right. Co-first author Dr. Adelaida Palla explained,

“When we gave mice a single shot of PGE2 directly to the muscle, it robustly affected muscle regeneration and even increased strength. Conversely, if we inhibited the ability of the muscle stem cells to respond to naturally produced PGE2 by blocking the expression of EP4 or by giving them a single dose of a nonsteroidal anti-inflammatory drug to suppress PGE2 production, the acquisition of strength was impeded.”

Their research not only adds more evidence against the using NSAID painkillers like ibuprofen and aspirin to treat sore muscles, but also suggests that PGE2 could be a natural therapeutic strategy to boost muscle regeneration.

This cross-section of regenerated muscle shows muscle stem cells (red) in their niche along the muscle fibers (green). (Photo courtesy of Blau lab)

PGE2 is already approved by the US Food and Drug Administration (FDA) to induce labor in pregnant women, and Dr. Blau hopes that further research in her lab will pave the way for repurposing PGE2 to treat muscle injury and other conditions.

“Our goal has always been to find regulators of human muscle stem cells that can be useful in regenerative medicine. It might be possible to repurpose this already FDA-approved drug for use in muscle. This could be a novel way to target existing stem cells in their native environment to help people with muscle injury or trauma, or even to combat natural aging.”

Throwback Thursday: Progress to a Cure for Diseases of Blindness

Welcome back to our “Throwback Thursday” series on the Stem Cellar. Over the years, we’ve accumulated an arsenal of exciting stem cell stories about advances towards stem cell-based cures for serious diseases. This month we’re featuring stories about CIRM-funded clinical trials for blindness.

2017 has been an exciting year for two CIRM-funded clinical trials that are testing stem cell-based therapies for diseases of blindness. A company called Regenerative Patch Technologies (RPT) is transplanting a sheet of embryonic stem cell-derived retinal support cells into patients with the dry form of age-related macular degeneration, a disease that degrades the eye’s macula, the center of the retina that controls central vision. The other trial, sponsored by a company called jCyte, is using human retinal progenitor cells to treat retinitis pigmentosa, a rare genetic disease that destroys the light-sensing cells in the retina, causing tunnel vision and eventually blindness.

 

Both trials are in the early stages, testing the safety of their respective stem cell therapies. But the teams are hopeful that these treatments will stop the progression of or even restore some form of vision in patients. In the past few months, both RPT and jCyte have shared exciting news about the progress of these trials which are detailed below.

Macular Degeneration Trial Gets a New Investor

In April, RPT announced that they have a new funding partner to further develop their stem cell therapy for age-related macular degeneration (AMD). They are partnering with Japan’s Santen Pharmaceutical Company, which specializes in developing ophthalmology or eye therapies.

AMD is the leading cause of blindness in elderly people and is projected to affect almost 200 million people worldwide by 2020. There is no cure or treatment that can restore vision in AMD patients, but stem cell transplants offer a potential therapeutic option.

RPT believes that their newfound partnership with Santen will accelerate the development of their stem cell therapy and ultimately fulfill an unmet medical need. RPT’s co-founder, Dr. Dennis Clegg, commented in a CIRM news release, “the ability to partner with a global leader in ophthalmology like Santen is very exciting. Such a strong partnership will greatly accelerate RPT’s ability to develop our product safely and effectively.”

This promising relationship highlights CIRM’s efforts to partner our clinical programs with outside investors to boost their chance of success. It also shows confidence in the future success of RPT’s stem cell-based therapy for AMD.

Retinitis Pigmentosa Trial Advances to Phase 2 and Receives RMAT Status

In May, the US Food and Drug Administration (FDA) approved jCyte’s RP trial for Regenerative Medicine Advanced Therapy (RMAT) status, which could pave the way for accelerated approval of this stem cell therapy for patients with RP.

RMAT is a new status established under the 21st Century Cures Act – a law enacted by Congress in December of 2016 to address the need for a more efficient regulatory approval process for stem cell therapies that can treat serious or life-threatening diseases. Trial sponsors of RMAT designated therapies can meet with the FDA earlier in the trial process and are eligible for priority review and accelerated approval.

jCyte’s RMAT status is well deserved. Their Phase 1 trial was successful, proving the treatment was safe and well-tolerated in patients. More importantly, some of the patients revealed that their sight has improved following their stem cell transplant. We’ve shared the inspiring stories of two patients, Rosie Barrero and Kristin Macdonald, previously on the Stem Cellar.

Rosie Barrero

Kristin MacDonald

Both Rosie and Kristin were enrolled in the Phase 1 trial and received an injection of retinal progenitor cells in a single eye. Rosie said that she went from complete darkness to being able to see shapes, colors, and the faces of her family and friends. Kristin was the first patient treated in jCyte’s trial, and she said she is now more sensitive to light and can see shapes well enough to put on her own makeup.

Encouraged by these positive results, jCyte launched its Phase 2 trial in April with funding from CIRM. They will test the same stem cell therapy in a larger group of 70 patients and monitor their progress over the next year.

Progress to a Cure for Blindness

We know very well that scientific progress takes time, and unfortunately we don’t know when there will be a cure for blindness. However, with the advances that these two CIRM-funded trials have made in the past year, our confidence that these stem cell treatments will one day benefit patients with RP and AMD is growing.

I’ll leave you with an inspiring video of Rosie Barrero about her experience with RP and how participating in jCytes trial has changed her life. Her story is an important reminder of why CIRM exists and why supporting stem cell research in particular, and research in general, is vital for the future health of patients.


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Latest space launch sends mice to test bone-building drug

Illustration of mice adapting to their custom-designed space habitat on board the International Space Station. Image courtesy of the Center for the Advancement of Science in Space

Astronauts on the International Space Station (ISS) received some furry guests this weekend with the launch of SpaceX’s Dragon supply capsule. On Saturday June 3rd, 40 mice were sent to the ISS along with other research experiments and medical equipment. Scientists will be treating the mice with a bone-building drug in search of a new therapy to combat osteoporosis, a disease that weakens bones and affects over 200 million people globally.

The bone-building therapy comes out of CIRM-funded research by UCLA scientists Dr. Chia Soo, Dr. Kang Ting and Dr. Ben Wu. Back in 2015, the UCLA team published that a protein called NELL-1 stimulates bone-forming stem cells, known as mesenchymal stem cells, to generate new bone tissue more efficiently in mice. They also found that NELL-1 blocked the function of osteoclasts – cellular recycling machines that break down and absorb bone – thus increasing bone density in mice.

Encouraged by their pre-clinical studies, the team decided to take their experiments into space. In collaboration with NASA and a grant from the Center for the Advancement of Science in Space (CASIS), they made plans to test NELL-1’s effects on bone density in an environment where bone loss is rapidly accelerated due to microgravity conditions.

Bone loss is a major concern for astronauts living in space for extended periods of time. The earth’s gravity puts pressure on our bones, stimulating bone-forming cells called osteoblasts to create new bone. Without gravity, osteoblasts stop functioning while the rate of bone resorption increases by approximately 1.5% per month. This translates to almost a 10% loss in bone density for every 6 months in space.

In a UCLA news release, Dr. Wu explained how they modified the NELL-1 treatment to stand up to the tests of space:

“To prepare for the space project and eventual clinical use, we chemically modified NELL-1 to stay active longer. We also engineered the NELL-1 protein with a special molecule that binds to bone, so the molecule directs NELL-1 to its correct target, similar to how a homing device directs a missile.”

The 40 mice will receive NELL-1 injections for four weeks on the ISS, at which point, half of the mice will be sent back to earth to receive another four weeks of NELL-1 treatment. The other half will stay in space and receive the same treatment so the scientists can compare the effects of NELL-1 in space and on land.

The Rodent Research Hardware System includes three modules: Habitat, Transporter, and Animal Access Unit.
Credits: NASA/Dominic Hart

The UCLA researchers hope that NELL-1 will prevent bone loss in the space mice and could lead to a new treatment for bone loss or bone injury in humans. Dr. Soo explained in an interview with SpaceFlight Now,

“We are hoping this study will give us some insights on how NELL-1 can work under these extreme conditions and if it can work for treating microgravity-related bone loss, which is a very accelerated, severe form of bone loss, then perhaps it can (be used) for patients one day on Earth who have bone loss due to trauma or due to aging or disease.”

If you want to learn more about this study, watch this short video below provided by UCLA. 

ViaCyte Advances Cell Replacement Therapy for High Risk Type 1 Diabetes

San Diego regenerative medicine company ViaCyte announced this week that the Food and Drug Administration (FDA) approved their Investigational New Drug (IND) Application for PEC-Direct, a cell-based therapy to treat patients at risk for severe complications caused by type 1 diabetes. In the US, IND approval is the final regulatory step required before a therapy can be tested in clinical trials.

PEC-Direct is a combination therapy consisting of cells encapsulated in a device that aims to replace the insulin-producing islet cells of the pancreas destroyed in patients with type 1 diabetes. The device contains human stem cell-derived pancreatic progenitor cells that develop into insulin-secreting cells when the device is placed under the patient’s skin. Ports on the surface of the device allow blood vessels from the host to directly contact the cells within, allowing for engraftment of the transplanted cells and for their maturation into islet cells.  These cells can sense and regulate blood glucose levels by secreting the hormones found in islets, including insulin.

ViaCyte’s PEC-Direct device allows a patient’s blood vessels to integrate and make contact with the transplanted cells.

Because PEC-Direct allows for “direct vascularization”, in effect connecting the device to the blood system, patients will need to take immunosuppressive drugs to prevent rejection of the donor cells. ViaCyte is therefore testing this therapy in patients who are at risk for serious complications associated with type 1 diabetes like severe hypoglycemia where a patient’s blood sugar is so low they need immediate medical assistance.

Severe hypoglycemia can occur because people with diabetes must inject insulin to control elevated blood sugar, but the injections can exceed the patients’ needs. The resulting low blood sugar can lead to dizziness, irregular heartbeat, and unconsciousness, even death. In some cases, sufferers are not aware of their hypoglycemia symptoms, putting them at increased risk of these life-threatening complications.

ViaCyte’s President and CEO, Dr. Paul Laikind, explained in a news release,

Paul Laikind

“While insulin therapy transformed type 1 diabetes from a death sentence to a chronic illness, it is far from a cure. Type 1 diabetes patients continue to deal with the daily impact of the disease and remain at risk for often severe long-term complications.  This is especially true for the patients with high-risk type 1 diabetes, who face challenges such as hypoglycemia unawareness and life-threatening severe hypoglycemic episodes.  These patients have a particularly urgent unmet medical need and could benefit greatly from cell replacement therapy.”

Approximately 140,000 people in the US and Canada suffer from this form of high-risk diabetes. These patients qualify for islet transplants from donated cadaver tissue. But because donor islets are in limited supply, ViaCyte Clinical Advisor, Dr. James Shapiro at the University of Alberta, believes PEC-Direct will address this issue by providing an unlimited supply of cells.

“Islet transplants from scarce organ donors have offered great promise for those with unstable, high-risk type 1 diabetes, but the procedure has many limitations.  With an unlimited supply of new islets that the stem cell-derived therapy promises, we have real potential to benefit far more patients with islet cell replacement.”

The company’s preclinical research on PEC-Direct, leading up to the FDA’s IND approval, was funded by a CIRM late stage preclinical grant. ViaCyte now plans to launch a clinical trial this year that will evaluate the safety and efficacy of PEC-Direct in the US and Canada. They will enroll approximately 40 patients at multiple clinical trial centers including the University of Alberta in Edmonton, the University of Minnesota, and UC San Diego. The trial will test whether the device is safe and whether the transplanted cells can produce enough insulin to relieve patients of insulin injections and hypoglycemic events.

ViaCyte has another product called PEC-Encap, a different implantable device that contains the same cells but protects these cells from the patient’s immune system. The device is being tested in a CIRM-funded Phase 1/2a trial, and ViaCyte is currently collaborating with W. L. Gore & Associates to improve the design of PEC-Encap to improve consistency of engraftment in patients.

Bridging the Gap: Regenerating Injured Bones with Stem Cells and Gene Therapy

Scientists from Cedars-Sinai Medical Center have developed a new stem cell-based technology in animals that mends broken bones that can’t regenerate on their own. Their research was published today in the journal Science Translational Medicine and was funded in part by a CIRM Early Translational Award.

Over two million bone grafts are conducted every year to treat bone fractures caused by accidents, trauma, cancer and disease. In cases where the fractures are small, bone can repair itself and heal the injury. In other cases, the fractures are too wide and grafts are required to replace the missing bone.

It sounds simple, but the bone grafting procedure is far from it and can cause serious problems including graft failure and infection. People that opt to use their own bone (usually from their pelvis) to repair a bone injury can experience intense pain, prolonged recovery time and are at risk for nerve injury and bone instability.

The Cedars-Sinai team is attempting to “bridge the gap” for people with severe bone injuries with an alternative technology that could replace the need for bone grafts. Their strategy combines “an engineering approach with a biological approach to advance regenerative engineering” explained co-senior author Dr. Dan Gazit in a news release.

Gazit’s team developed a biological scaffold composed of a protein called collagen, which is a major component of bone. They implanted these scaffolds into pigs with fractured leg bones by inserting the collagen into the gap created by the bone fracture. Over a two-week period, mesenchymal stem cells from the animal were recruited into the collagen scaffolds.

To ensure that these stem cells generated new bone, the team used a combination of ultrasound and gene therapy to stimulate the stem cells in the collagen scaffolds to repair the bone fractures. Ultrasound pulses, or high frequency sound waves undetectable by the human ear, temporarily created small holes in the cell membranes allowing the delivery of the gene therapy-containing microbubbles into the stem cells.

Image courtesy of Gazit Group/Cedars-Sinai.

Animals that received the collagen transplant and ultrasound gene therapy repaired their fractured leg bones within two months. The strength of the newly regenerated bone was comparable to successfully transplanted bone grafts.

Dr. Gadi Pelled, the other senior author on this study, explained the significance of their research findings for treating bone injuries in humans,

“This study is the first to demonstrate that ultrasound-mediated gene delivery to an animal’s own stem cells can effectively be used to treat non-healing bone fractures. It addresses a major orthopedic unmet need and offers new possibilities for clinical translation.”

You can learn more about this study by watching this research video provided by the Gazit Group at Cedars-Sinai.


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Kidney Disease: There’s an Organ-on-a-Chip for That

“There’s an app for that” is a well-known phrase trademarked by Apple to promote how users can do almost anything they do on a computer on their mobile phone. Apps are so deeply ingrained in everyday life that it’s hard for some people to imagine living without them. (I know I’d be lost without google maps or my Next Bus app!)

An estimated 2.2 million mobile apps exist for iPhones. Imagine if this multitude of apps were instead the number of stem cell models available for scientists to study human biology and disease. Scientists dream of the day when they can respond to questions about any disease and say, “there’s a model for that.” However, a future where every individual or disease has its own personalized stem cell line is still far away.

In the meantime, scientists are continuing to generate stem cell-based technologies that answer important questions about how our tissues and organs function and what happens when they are affected by disease. One strategy involves growing human stem cells on microchips and developing them into miniature organ systems that function like the organs in our bodies.

Kidney-on-a-chip

A group of scientists from Harvard’s Wyss Institute are using organ-on-a-chip technology to model a structure in the human kidney, called a glomerulus, that’s essential for filtering the body’s blood. It’s made up of a meshwork of blood vessels called capillaries that remove waste, toxic products, and excess fluid from the blood by depositing them into the urine.

The glomerulus also contains cells called podocytes that wrap around the capillaries and leave thin slits for blood to filter through. Diseases that affect podocytes or the glomerulus structure can cause kidney failure early or later in life, which is why the Harvard team was so interested to model this structure using their microchip technology.

They developed a method to mature human pluripotent stem cells into podocytes by engineering an environment similar to that of a real kidney on a microchip. Using a combination of kidney-specific factors and extracellular matrix molecules, which form a supportive environment for cells within tissues and organs, the team generated mature podocytes from human stem cells in three weeks. Their study was published in Nature Biomedical Engineering and was led by Dr. Donald Ingber, Founding Director of the Wyss Institute.

3D rendering of the glomerulus-on-a-chip derived from human stem cells. (Wyss Institute at Harvard University)

First author, Samaira Musah, explained how their glomerulus-on-a-chip works in a news release,

“Our method not only uses soluble factors that guide kidney development in the embryo, but, by growing and differentiating stem cells on extracellular matrix components that are also contained in the membrane separating the glomerular blood and urinary systems, we more closely mimic the natural environment in which podocytes are induced and mature. We even succeeded in inducing much of this differentiation process within a channel of the microfluidic chip, where by applying cyclical motions that mimic the rhythmic deformations living glomeruli experience due to pressure pulses generated by each heartbeat, we achieve even greater maturation efficiencies.”

Over 90% of stem cells successfully developed into functional podocytes that could properly filter blood by selectively filtering different blood proteins. The podocytes also were susceptible to a chemotherapy drug called doxorubicin, proving that they are suitable for modeling the effects of drug toxicity on kidneys.

Kidney podocyte derived from human stem cells. (Wyss Institute)

Ingber highlighted the potential applications of their glomerulus-on-a-chip technology,

Donald Ingber, Wyss Institute

“The development of a functional human kidney glomerulus chip opens up an entire new experimental path to investigate kidney biology, carry out highly personalized modeling of kidney diseases and drug toxicities, and the stem cell-derived kidney podocytes we developed could even offer a new injectable cell therapy approach for regenerative medicine in patients with life-threatening glomerulopathies in the future.”

There’s an organ-on-a-chip for that!

The Wyss Institute team has developed other organ-on-chips including lungs, intestine, skin and bone marrow. These miniature human systems are powerful tools that scientists hope will “revolutionize drug development, disease modeling and personalized medicine” by reducing the cost of research and the reliance on animal models according to the Wyss Institute technology website.

What started out as a microengineering experiment in Ingber’s lab a few years ago is now transforming into a technology “that is now poised to have a major impact on society” Ingber further explained. If organs-on-chips live up to these expectations, you might one day hear a scientist say, “Don’t worry, there’s an organ-on-a-chip for that!”


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