Rare Disease Gets Big Boost from California’s Stem Cell Agency

UC Irvine’s Dr. Leslie Thompson and patient advocate Frances Saldana after the CIRM Board vote to approve funding for Huntington’s disease

If you were looking for a poster child for an unmet medical need Huntington’s disease (HD) would be high on the list. It’s a devastating disease that attacks the brain, steadily destroying the ability to control body movement and speech. It impairs thinking and often leads to dementia. It’s always fatal and there are no treatments that can stop or reverse the course of the disease. Today the Board of the California Institute for Regenerative Medicine (CIRM) voted to support a project that shows promise in changing that.

The Board voted to approve $6 million to enable Dr. Leslie Thompson and her team at the University of California, Irvine to do the late stage testing needed to apply to the US Food and Drug Administration for permission to start a clinical trial in people. The therapy involves transplanting stem cells that have been turned into neural stem cells which secrete a molecule called brain-derived neurotrophic factor (BDNF), which has been shown to promote the growth and improve the function of brain cells. The goal is to slow down the progression of this debilitating disease.

“Huntington’s disease affects around 30,000 people in the US and children born to parents with HD have a 50/50 chance of getting the disease themselves,” says Dr. Maria T. Millan, the President and CEO of CIRM. “We have supported Dr. Thompson’s work for a number of years, reflecting our commitment to helping the best science advance, and are hopeful today’s vote will take it a crucial step closer to a clinical trial.”

Another project supported by CIRM at an earlier stage of research was also given funding for a clinical trial.

The Board approved almost $12 million to support a clinical trial to help people undergoing a kidney transplant. Right now, there are around 100,000 people in the US waiting to get a kidney transplant. Even those fortunate enough to get one face a lifetime on immunosuppressive drugs to stop the body rejecting the new organ, drugs that increase the risk for infection, heart disease and diabetes.  

Dr. Everett Meyer, and his team at Stanford University, will use a combination of healthy donor stem cells and the patient’s own regulatory T cells (Tregs), to train the patient’s immune system to accept the transplanted kidney and eliminate the need for immunosuppressive drugs.

The initial group targeted in this clinical trial are people with what are called HLA-mismatched kidneys. This is where the donor and recipient do not share the same human leukocyte antigens (HLAs), proteins located on the surface of immune cells and other cells in the body. Around 50 percent of patients with HLA-mismatched transplants experience rejection of the organ.

In his application Dr. Meyer said they have a simple goal: “The goal is “one kidney for life” off drugs with safety for all patients. The overall health status of patients off immunosuppressive drugs will improve due to reduction in side effects associated with these drugs, and due to reduced graft loss afforded by tolerance induction that will prevent chronic rejection.”

The most popular Stem Cellar posts of 2018

The blog

You never know when you write something if people are going to read it. Sometimes you wonder if anyone is going to read it. So, it’s always fun, and educational, to look back at the end of the year and see which pieces got the most eyeballs.

It isn’t always the ones you think will draw the biggest audiences. Sometimes it is diseases that are considered “rare” (those affecting fewer than 200,000 people) that get the most attention.

Maybe it’s because those diseases have such a powerful online community which shares news, any news, about their condition of interest with everyone they know. Whatever the reason, we are always delighted to share encouraging news about research we are funding or encouraging research that someone else is funding.

That was certainly the case with the top two stories this year. Both were related to ALS or Lou Gehrig’s disease.  It’s a particularly nasty condition. People diagnosed with ALS have a life expectancy of just 2 to 5 years. So it’s probably not a big surprise that stories suggesting stem cells could expand that life span got a big reception.

Whatever the reason, we’re just happy to share hopeful news with everyone who comes to our blog.

And so, without further ado, here is the list of the most popular Stem Cellar Blog Posts for 2018.

All of us in the Communications team at CIRM consider it an honor and privilege to be able to work here and to meet many of the people behind these stories; the researchers and the patients and patient advocates. They are an extraordinary group of individuals who help remind us why we do this work and why it is important. We love our work and we hope you enjoy it too. We plan to be every bit as active and engaged in 2019.

CIRM-funded medical research and development company does $150M deal to improve care for dialysis patients

Fresenius & Humacyte

Nearly half a million Americans with kidney disease are on dialysis, so it’s not surprising the CIRM Board had no hesitation, back in July 2016, in funding a program to make it easier and safer to get that life-saving therapy.

That’s why it’s gratifying to now hear that Humacyte, the company behind this new dialysis device, has just signed a $150 million deal with Fresenius Medical Care, to make their product more widely available.

The CIRM Board gave Humacyte $10 million for a Phase 3 clinical trial to test a bioengineered vein needed by people undergoing hemodialysis, the most common form of dialysis.

Humacyte HAV

The vein – called a human acellular vessel or HAV – is implanted in the arm and used to carry the patient’s blood to and from an artificial kidney that removes waste from the blood. Current synthetic versions of this device have many problems, including clotting, infections and rejection. In tests, Humacyte’s HAV has fewer complications. In addition, over time the patient’s own stem cells start to populate the bioengineered vein, in effect making it part of the patient’s own body.

Fresenius Medical Care is investing $150 million in Humacyte, with a plan to use the device in its dialysis clinics worldwide. As an indication of how highly they value the device, the deal grants Fresenius a 19% ownership stake in the company.

In an interview with FierceBiotech, Jeff Lawson, Humacyte’s Chief Medical Officer, said if all goes well the company plans to file for Food and Drug Administration (FDA) approval in 2019 and hopes it will be widely available in 2020.

In addition to being used for kidney disease the device is also being tested for peripheral artery disease, vascular trauma and other cardiovascular indications. Lawson says testing the device first in kidney disease will provide a solid proving ground for it.

“It’s a very safe place to develop new vascular technologies under clinical study. From a regulatory safety standpoint, this is the first area we could enter safely and work with the FDA to get approval for a complete new technology.”

This is another example of what we call CIRM’s “value proposition”; the fact that we don’t just provide funding, we also provide support on many other levels and that has a whole range of benefits. When our Grants Working Group – the independent panel of experts who review our scientific applications – and the CIRM Board approves a project it’s like giving it the CIRM Good Housekeeping Seal of Approval. That doesn’t just help that particular project, it can help attract further investment in the company behind it, enabling it to expand operations and create jobs and ultimately, we hope, help advance the field as a whole.

Those benefits are substantial. To date we have been able to use our funding to leverage around $2 billion in additional dollars in terms of outside companies investing in companies like Humacyte, or researchers using data from research we funded to get additional funding from agencies like the National Institutes of Health.

So, when a company like Humacyte is the object of such a lucrative agreement it’s not just a compliment to the quality of the work they do, it’s also a reflection of our ability to pick great projects.

Stem cell study holds out promise for kidney disease

Kidney failure

Image via youtube.com

Kidney failure is the Rodney Dangerfield of diseases, it really doesn’t get the respect it deserves. An estimated 660,000 Americans suffer from kidney failure and around 47,000 people die from it every year. That’s more than die from breast or prostate cancer. But now a new study has identified a promising stem cell candidate that could help in finding a way to help repair damaged kidneys.

Kidneys are the body’s waste disposal system, filtering our blood and cleaning out all the waste products. Our kidneys have a limited ability to help repair themselves but if someone suffers from chronic kidney disease then their kidneys are slowly overwhelmed and that leads to end stage renal disease. At that point the patient’s options are limited to dialysis or an organ transplant.

Survivors hold out hope

Italian researchers had identified some cells in the kidneys that showed a regenerative ability. These cells, which were characterized by the expression of a molecule called CD133, were able to survive injury and create different types of kidney cells.

Researchers at the University of Torino in Italy decided to take these findings further and explore precisely how CD133 worked and if they could take advantage of that and use it to help repair damaged kidneys.

In their findings, published in the journal Stem Cells Translational Medicine, the researchers began by working with a chemotherapy drug called cisplatin, which is used against a broad range of cancers but is also known to cause damage to kidneys in around one third of all patients. The team found that CD133 was an important factor in helping those damaged kidneys recover. They also found that CD133 prevents aging of kidney progenitor cells, the kind of cell needed to help create new cells to repair the kidneys in future.

Hope for further research

The finding opens up a number of possible lines of research, including exploring whether infusions of CD133 could help patients whose kidneys are no longer able to produce enough of the molecule to help repair damage.

In an interview in DD News, Dr. Anthony Atala, Director of the Wake Forest Institute for Regenerative Medicine – praised the research:

“This is an interesting and novel finding. Because the work identifies mechanisms potentially involved in the repair of tissue after injury, it suggests the possibility of new therapies for tissue repair and regeneration.”

CIRM is funding several projects targeting kidney disease including four clinical trials for kidney failure. These are all late-stage kidney failure problems so if the CD133 research lives up to its promise it might be able to help people at an earlier stage of disease.

CIRM-Funded Clinical Trials Targeting the Heart, Pancreas, and Kidneys

This blog is part of our Month of CIRM series, which features our Agency’s progress towards achieving our mission to accelerate stem cell treatments to patients with unmet medical needs.

This week, we’re highlighting CIRM-funded clinical trials to address the growing interest in our rapidly expanding clinical portfolio. Today we are featuring trials in our organ systems portfolio, specifically focusing on diseases of the heart/vasculature system, the pancreas and the kidneys.

CIRM has funded a total of nine trials targeting these disease areas, and eight of these trials are currently active. Check out the infographic below for a list of our currently active trials.

For more details about all CIRM-funded clinical trials, visit our clinical trials page and read our clinical trials brochure which provides brief overviews of each trial.

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.


Related Links:

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!”


Related Links:

Stem Cells Profiles in Courage: Frank’s final gift

frank-st-clair

Not every story has a happy ending. But they do all have something to teach us. In the case of Frank St. Clair the lesson was simple: live life fully and freely, love those around you, and never give up.

We were fortunate enough to get to know Frank as one of the people we profiled in our 2016 Annual Report. Frank was a patient in a clinical trial we are funding to test a new kind of bioengineered vein needed by people undergoing hemodialysis, the most common form of dialysis.

It was an all too brief friendship. Frank passed away on December 17th due to complications from heart disease. But in that time he touched us with his warmth, his kindness, his sense of humor and his generosity. Frank never gave up. He kept fighting to the end. His courage, and compassion for others is a reminder to us that we need to work as hard as we can, to bring treatments to those who need them most.

This is Frank’s story, in his own words:

“I have kidney disease. Had it about four years. When I first started dialysis I had a shunt in my chest.  I had to be careful with the shunt, especially at night, in case I pulled it out. It kept clogging up on me and I’d have to go in and get it reopened and that was a terrible thing.

One time when they were opening up the shunt in my chest I ran into the doctor and I got talking to him. He knew how miserable I was and he asked if I wanted to take part in this clinical trial. I said I did and they arranged for me to get this, the device. I just lucked out and was in the right place at the right time. Best move I ever made. Didn’t know anything about stem cells then, sure didn’t, I just knew I was miserable and if there was any way to make life better I just wanted to do it or try it.

And then I did this and it was like day and night.

Since I’ve done this my life has improved 100%. I can do a lot now that I couldn’t do before. My wife and I are so grateful that we can have this. Now we can go out to dinner and do anything we want. We could go out before but we had to always be careful because of the thing in my chest. But now I don’t even think about it. It’s like getting my life back.

I don’t notice it all. I don’t feel it at all. I hate to say it, but I can’t believe I’m on dialysis. I would like to have a kidney but I’ll be honest with you this is the next best thing.

When I go to the clinic there’s a lot of old people there and I just try to make them laugh, tell them jokes, I just can’t believe how good I feel and I want to make others feel good too.

I take the time to talk to them, and give them gum and that cheers them up. My wife has to keep me supplied with gum.

I’ve been married 45 years. We met in high school chorus. I didn’t care too much about singing but I went to chorus because I wanted to meet girls. That’s where I met Paula. Best move I ever made.

I sure don’t feel old. My wife and I are two people that love each other very dearly, that’s my blessing, with her help I couldn’t get old.

I’m a workaholic but until I got the Humacyte device I couldn’t work. I had to sell my business.

I used to be a private detective. It had its moments. My wife used to get mad because I got up at 2 or 3 in the morning to get someone who was in hiding. I had one guy, he was about 6’ 7”, big guy. I knocked at the door and said the name of the guy I was looking for, and asked if he was there. He asked why, so I told him why I was there and he said “It’s me,” and ran right over me and knocked me on the ground and ran away. But I managed to talk him into coming back.

We served a lot of papers on foreclosures and I hated that, and I would always try and help those people if I could.

One time I ran into an old lady, she was a nice woman, and her husband handled all the bills but he died and they had stock in Bernie Madoff’s company and when he went under it left her broke.  They had $1.7 million in a company that went bankrupt. She lost it all. She didn’t know what to do. When I went to serve her papers she hadn’t eaten in two days,  so I went and bought her and brought some groceries and made sure the electric bill got paid and then called her son and made sure she was taken care of.

My wife said we were going broke helping so many people, but I felt that if you help people it comes back to you and it has.

I volunteer at the VA, help out there when I can. Just trying to give back. Always have. I think if you can help someone you need to do it.

I feel damn lucky, really lucky, more ways than one. You have to understand I have lived 50 years longer than I should have; I could have died in Vietnam, so I would just say do not give up. Don’t give up. My wife wouldn’t let me give up, and things happen. If they are meant to be, of course. Something will happen and I’m telling you. The key is making people around you feel like they want to be around you.”

We are forever grateful to Frank for being willing to be part of a clinical trial that will, hopefully, improve the quality of life for many others. That is his legacy. Our thoughts and wishes go out to his wife Paula

California’s stem cell agency rounds up the year with two more big hits

icoc_dec2016-17

CIRM Board meeting with  Jake Javier, CIRM Chair Jonathan Thomas, Vice Chair Sen. Art Torres (Ret.) and President/CEO Randy Mills

It’s traditional to end the year with a look back at what you hoped to accomplish and an assessment of what you did. By that standard 2016 has been a pretty good year for us at CIRM.

Yesterday our governing Board approved funding for two new clinical trials, one to help kidney transplant patients, the second to help people battling a disease that destroys vision. By itself that is a no small achievement. Anytime you can support potentially transformative research you are helping advance the field. But getting these two clinical trials over the start line means that CIRM has also met one of its big goals for the year; funding ten new clinical trials.

If you had asked us back in the summer, when we had funded only two clinical trials in 2016, we would have said that the chances of us reaching ten trials by the end of the year were about as good as a real estate developer winning the White House. And yet……..

Helping kidney transplant recipients

The Board awarded $6.65 million to researchers at Stanford University who are using a deceptively simple approach to help people who get a kidney transplant. Currently people who get a transplant have to take anti-rejection medications for the rest of their life to prevent their body rejecting the new organ. These powerful immunosuppressive medications are essential but also come with a cost; they increase the risk of cancer, infection and heart disease.

icoc_dec2016-3

CIRM President/CEO Randy Mills addresses the CIRM Board

The Stanford team will see if it can help transplant patients bypass the need for those drugs by injecting blood stem cells and T cells (which play an important role in the immune system) from the kidney donor into the kidney recipient. The hope is by using cells from the donor, you can help the recipient’s body more readily adjust to the new organ and reduce the likelihood the body’s immune system will attack it.

This would be no small feat. Every year around 17,000 kidney transplants take place in the US, and many people who get a donor kidney experience fevers, infections and other side effects as a result of taking the anti-rejection medications. This clinical trial is a potentially transformative approach that could help protect the integrity of the transplanted organ, and improve the quality of life for the kidney recipient.

Fighting blindness

The second trial approved for funding is one we are already very familiar with; Dr. Henry Klassen and jCyte’s work in treating retinitis pigmentosa (RP). This is a devastating disease that typically strikes before age 30 and slowly destroys a person’s vision. We’ve blogged about it here and here.

Dr. Klassen, a researcher at UC Irvine, has developed a method of injecting what are called retinal progenitor cells into the back of the eye. The hope is that these cells will repair and replace the cells damaged by RP. In a CIRM-funded Phase 1 clinical trial the method proved safe with no serious side effects, and some of the patients also reported improvements in their vision. This raised hopes that a Phase 2 clinical trial using a larger number of cells in a larger number of patients could really see if this therapy is as promising as we hope. The Board approved almost $8.3 million to support that work.

Seeing is believing

How promising? Well, I recently talked to Rosie Barrero, who took part in the first phase clinical trial. She told me that she was surprised how quickly she started to notice improvements in her vision:

“There’s more definition, more colors. I am seeing colors I haven’t seen in years. We have different cups in our house but I couldn’t really make out the different colors. One morning I woke up and realized ‘Oh my gosh, one of them is purple and one blue’. I was by myself, in tears, and it felt amazing, unbelievable.”

Amazing was a phrase that came up a lot yesterday when we introduced four people to our Board. Each of the four had taken part in a stem cell clinical trial that changed their lives, even saved their lives. It was a very emotional scene as they got a chance to thank the group that made those trials, those treatments possible.

We’ll have more on that in a future blog.

 

 

 

 

Bioengineered veins give hope to kidney disease patients on dialysis

As blood travels around your body, it helps your body get around. Blood is essential for delivering oxygen and nutrients to all the cells in your body and for removing waste products made by these cells. Your body contains approximately 1.5 gallons of blood, which translates to around 7% of your body weight. In order for all this blood to do its job, it needs to be constantly cleaned of waste and extra fluids.

Your kidneys are your blood’s best friend. They act as natural filters that remove those cellular waste products and extra fluid from the blood and pass them off to the bladder, where they are disposed of through urine. Kidneys have the important job of maintaining the proper balance of fluids, electrolytes and chemicals in the blood. They are also involved in other essential biological processes such as regulating blood pressure, making new blood cells, and maintaining healthy bones. It’s a big problem when your kidneys stop working. Without this built-in filtration system, toxic byproducts build up in your blood and cause a multitude of not fun symptoms.

Hemodialysis acts as an artificial kidney to filter the blood of kidney disease patients. (wikipedia)

Hemodialysis acts as an artificial kidney to filter the blood of kidney disease patients. (wikipedia)

More than half a million Americans suffering from kidney dysfunction or failure are being treated by hemodialysis. This process involves connecting a patient to a machine that acts as an artificial kidney. “Old blood” is pumped into the machine from a plastic tube, also known as a shunt, that’s inserted into the patient’s vein. The blood is then passed through a dialyzer which filters out the waste products and extra fluid and allows clean blood to pass through and be put back into the patient (see image).

While hemodialysis is successful at extending the lifespan of kidney disease patients, serious complications can arise from this treatment including uncontrolled changes in blood pressure, bone disease, and anemia. Another common problem occurs with the shunt that’s inserted into a patient’s vein. Shunts can cause infection, blood clots, and can also be rejected by a patient’s immune system. As a result, patients have to get new shunts implanted every year. This is not always feasible for older patients whose veins cannot hold up to this invasive procedure.

A tubular alternative for better hemodialysis

A North Carolina company called Humacyte is trying to improve current hemodialysis technology by engineering human acellular vessels (HAVs) (meaning that the vessels don’t have any cells) that can be transplanted into patients and develop into a human version of a shunt. Sounds complicated, but it’s not really!

First, scientists take muscle cells from human organ donors and coax these cells to grow into tube-like structures. During this process, the cells secrete a compound called cellulose – a component of the extracellular matrix – which forms a biological scaffold that maintains the structure of the cells.

Next, the scientists chemically wash away the muscle cells, leaving an intact scaffold with a hole the diameter of your pinky finger. These scaffolds are then placed under the skin of patients on dialysis. Once transplanted, a patient’s own stem cells migrate to the empty scaffold, set up shop and create a new vein with a wide enough hole that can be used for hemodialysis.

Humacyte’s Chief Medical Officer, Jeff Lawson, explained it an interview with KQED Science:

Jeff Lawson, Humacyte

Jeff Lawson, Humacyte

“This scaffold, once implanted, uniquely becomes repopulated with their own stem cells. That then turns back into something that looks like a vascular cell. And it now transitions over the period of a few months into something that’s indistinguishable from your own tissue. One of the holy grails in vascular surgery is to come up with a prosthetic artificial graft that has the same properties as the patient’s own blood vessels.”

The great news about this promising technology is that Humacyte is testing it in a Phase III clinical trial – the final stage before a drug or treatment is approved by the US Food and Drug Administration (FDA). In a Phase III trial, the treatment has already proven to be safe and shown some effectiveness (in a Phase II trial) and is now being tested in a larger group of patients to hopefully confirm these findings.

In July, CIRM invested $10 million in Humacyte’s Phase III trial in hopes that this technology will improve the lives and health of dialysis patients. Randy Mills, the President and CEO of CIRM, views kidney failure as an unmet medical need that could benefit from a stem cell related treatment:

“This approach has the potential to significantly improve our ability to care for people with kidney disease. Being able to reduce infections and clotting problems, and increase the consistency of care hemodialysis patients get, would meaningfully impact the quality of their lives.”

A patient’s story and CIRM’s efforts to fund clinical trials

Raymund Ramirez

Raymond Ramirez (KQED Science)

Yesterday, David Gorn from KQED Science published a nice piece about Humacyte’s stem cell derived technology and featured the story of a kidney failure patient, Raymond Ramirez. Raymond’s story is very emotional. He is a Vietnam war veteran that has experienced a gauntlet of maladies including bladder cancer and blindness in his right eye. On top of that, his kidneys aren’t functioning well and he is unable to continue his dialysis treatments because his veins aren’t holding up.

Raymond was the first patient to be treated in Humacyte’s Phase III trial. You can read more about his story here.

Gorn also highlighted CIRM’s recent efforts to fund promising stem cell projects that are further along in development and ready for clinical trials in patients. He ended with a quote from UC San Diego’s director of stem cell research, Larry Goldstein, on how important it is for our agency to continue funding stem cell clinical trials.

Larry Goldstein

Larry Goldstein

“Ten years ago I don’t think there were that many [stem cell] projects that were really ready for clinical trials. The field itself has developed projects that are at clinical stage. If the agency [CIRM] keeps pumping out these types of clinical results, California voters may soon see another ballot measure to keep it going.”