cartilage

Researchers develop a stem cell-based implant for cartilage restoration and treating osteoarthritis

/ Esteban Cortez / 3 Comments
The Plurocart’s scaffold membrane seeded with stem cell-derived chondrocytes. Image courtesy of USC Photo/Denis Evseenko.

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Researchers at the Keck School of Medicine of USC have used a stem cell-based bio-implant to repair cartilage and delay joint degeneration in a large animal model. This paves the way to potentially treat humans with cartilage injuries and osteoarthritis, which occurs when the protective cartilage at the ends of the bones wears down over time. The disorder affects millions worldwide.

 The researchers are using this technology to manufacture the first 64 implants to be tested on humans with support from a $6 million grant from the California Institute for Regenerative Medicine (CIRM).

Researchers Dr. Denis Evseenko, and Dr. Frank Petrigliano led the development of the therapeutic bio-implant, called Plurocart. It’s composed of a scaffold membrane seeded with stem cell-derived chondrocytes, the cells responsible for producing and maintaining healthy articular cartilage tissue. 

In the study, the researchers implanted the Plurocart membrane into a pig model of osteoarthritis, resulting in the long-term repair of articular cartilage defects. Evseenko said the findings are significant because the implant fully integrated in the damaged articular cartilage tissue and survived for up to six months. “Previous studies have not been able to show survival of an implant for such a long time,” Evseenko added.

The researchers also found that the cartilage tissue generated was strong enough to withstand compression and elastic enough to accommodate movement without breaking.

Osteoarthritis, an often-painful disorder, can affect any joint, but most commonly affects those in our knees, hips, hands and spine. The USC researchers hope their implant will help prevent the development of arthritis and alleviate the need for invasive joint replacement surgeries.

“Many of the current options for cartilage injury are expensive, involve complex logistical planning, and often result in incomplete regeneration,” said Petrigliano. “Plurocart represents a practical, inexpensive, one-stage therapy that may be more effective in restoring damaged cartilage and improve the outcome of such procedures.”

Read the full study here and learn more about the CIRM grant here.

Some good news for people with dodgy knees

/ Kevin McCormack / 1 Comment

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Graphic contrasting a healthy knee with one that has osteoarthritis

About 10% of Americans suffer from knee osteoarthritis, a painful condition that can really impair mobility and quality of life. It’s often caused by an injury to cartilage, say when you were playing sports in high school or college, and over time it continues to degenerate and ultimately results in the  loss of both cartilage and bone in the joint.

Current treatments involve either medication to control the pain or surgery. Medication works up to a point, but as the condition worsens it loses effectiveness.  Knee replacement surgery can be effective, but is a serious, complicated procedure with a long recovery time.  That’s why the governing Board of the California Institute for Regenerative Medicine (CIRM) voted to invest almost $6 million in an innovative stem cell therapy approach to helping restore articular cartilage in the knee.

Dr. Frank Petrigliano, Chief of the Epstein Family Center for Sports Medicine at Keck Medicine of the University of Southern California (USC), is using pluripotent stem cells to create chondrocytes (the cells responsible for cartilage formation) and then seeding those onto a scaffold. The scaffold is then surgically implanted at the site of damage in the knee. Based on scientific data, the seeded scaffold has the potential to regenerate the damaged cartilage, thus decreasing the likelihood of progression to knee osteoarthritis.  In contrast to current methods, this new treatment could be an off-the-shelf approach that would be less costly, easier to administer, and might also reduce the likelihood of progression to osteoarthritis.

This is a late-stage pre-clinical program. The goals are to manufacture clinical grade product, carry out extensive studies to demonstrate safety of the approach, and then file an IND application with the FDA, requesting permission to test the product in a clinical trial in people.

“Damage to the cartilage in our knees can have a big impact on quality of life,” says Dr. Maria T. Millan, MD, President and CEO of CIRM. “It doesn’t just cause pain, it also creates problems carrying out simple, everyday activities such as walking, climbing stairs, bending, squatting and kneeling. Developing a way to repair or replace the damaged cartilage to prevent progression to knee osteoarthritis could make a major difference in the lives of millions of Americans. This program is a continuation of earlier stage work funded by CIRM at the Basic Biology and Translational stages, illustrating how CIRM supports scientific programs from early stages toward the clinic.”

Researchers discover how to steer stem cells to regenerate cartilage in joints

/ Yimy Villa / Leave a comment
Dr. Charles K.F. Chan (Left) and Dr. Michael Longaker (right), Stanford University

Cartilage is a flexible, connective tissue in our joints that is important for cushioning our bones against impacts. This cartilage deteriorates as we age due to normal wear and tear and in some instances excessive damage or a deteriorating disease. The deterioration of cartilage is also the primary cause of joint pain and arthritis, which affects more than 55 million Americans.

It was generally assumed that adult cartilage could not be regenerated after damage. Fortunately, a CIRM funded project by Dr. Charles K.F. Chan, Dr. Michael Longaker, and Dr. Matthew Murphy at Stanford University found a way to use chemical signals to steer skeletal stem cells, which are responsible for the production of bone and cartilage, to regrow cartilage in joints.

Damaged cartilage is currently treated with a technique known as microfracture. Tiny holes are drilled into the surface of a joint, which activates the body’s skeletal stem cells to create fibrocartilage in the joint. Unfortunately, this newly created tissue lacks the flexible properties and cushion of normal cartilage.

The team theorized that there might be a way to influence skeletal stem cells to produce normal cartilage after microfracture. In a mouse model, the researchers used a molecule called BMP2 to initiate bone formation after microfracture. Next, they stopped the bone formation process midway with another molecule called VEGF. The result of this process was the generation of cartilage that had the same important properties as natural cartilage.

In a Stanford press release, Dr. Chan elaborated on these findings.

“What we ended up with was cartilage that is made of the same sort of cells as natural cartilage with comparable mechanical properties, unlike the fibrocartilage that we usually get. It also restored mobility to osteoarthritic mice and significantly reduced their pain.”

To show that this process could work in humans, the team then transferred human tissue into special mice that wouldn’t reject the tissue. They showed that human skeletal stem cells could be steered toward bone development but stopped at the cartilage stage.

The next stage for this research is to conduct experiments in larger animals before eventually starting human clinical trials. The ultimate goal of this treatment would be to help prevent arthritis by rejuvenating cartilage in the joints before it is badly degraded.

In the same press release, Dr. Longaker discusses the advantages of using BMP2 and VEGF for this process.

“BMP2 has already been approved for helping bone heal, and VEGF inhibitors are already used as anti-cancer therapies. This would help speed the approval of any therapy we develop.”

The full results of this study were published in Nature.

The Most Important Gift of All

/ Kevin McCormack / Leave a comment
Photo courtesy American Hospital Association

There are many players who have a key role in helping make a stem cell therapy work. The scientists who develop the therapy, the medical team who deliver it and funders like CIRM who provide the money to make this all happen. But vital as they are, in some therapies there is another, even more important group; the people who donate life-saving organs and tissues for transplant and research.

Organ and tissue donation saves lives, increases knowledge of diseases, and allow for the development of novel medications to treat them. When individuals or their families authorize donation for transplant or medical research, they allow their loved ones to build a long-lasting legacy of hope that could not be accomplished in any other way.

Four of CIRM’s clinical trials involve organ donations – three kidney transplant programs (you can read about those here, here and here) and one targeting type 1 diabetes.

Dr. Nikole Neidlinger, the Chief Medical Officer with Donor Network West – the federally designated organ and tissue recovery organization for Northern California and Nevada – says it is important to recognize the critical contribution made in a time of grief and crisis by the families of deceased donors. 

“For many families who donate, a loved one has died, and they are in shock. Even so, they are willing to say yes to giving others a second chance at life and to help others to advance science. Without them, none of this would be possible. It’s the ultimate act of generosity and compassion.”

The latest CIRM-funded clinical trial involving donated tissue is with Dr. Peter Stock and his team at UCSF. They are working on a treatment for type 1 diabetes (T1D), where the body’s immune system destroys its own pancreatic beta cells. These cells are necessary to produce insulin, which regulates blood sugar levels in the body.

In the past people have tried transplanting beta cells, from donated pancreatic islets, into patients with type 1 diabetes to try and reverse the course of the disease. However, this requires islets from multiple donors and the shortage of organ and tissue donors makes this difficult to do.

Dr. Stock’s clinical trial at UCSF aims to address these limitations.  He is going to transplant both pancreatic islets and parathyroid glands, from the same donor, into T1 patients. It’s hoped this combination approach will increase beta cell survival, potentially boosting long-term insulin production and removing the need for multiple donors.  And because the transplant is placed in the patient’s forearm, it makes it easier to monitor the effectiveness and accessibility of the islet transplants. Of equal importance, the development of this site will facilitate the transplantation of stem cell derived beta cells, which are very close to clinical application.

“As a transplant surgeon, it is an absolute privilege to be able to witness the life-saving organ transplants made possible by the selfless generosity of the donor families. It is hard to imagine how families have the will to think about helping others at a time of their greatest grief. It is this willingness to help others that restores my faith in humanity”

Donor Network West plays a vital role in this process. In 2018 alone, the organization recovered 702 donor samples for research. Thanks to the generosity of the donors/donor families, the donor network has been able to provide parathyroid and pancreas tissue essential to make this clinical trial a success”

“One organ donor can save the lives of up to eight people and a tissue donor can heal more than 75 others,” says Dr. Neidlinger. “For families, the knowledge that they are transforming someone’s life, and possibly preventing another family from experiencing this same loss, can serve as a silver lining during their time of sorrow. .”

Organs that can be donated

Kidney (x2), Heart, Lungs (x2), Liver, Pancreas, Intestine

Tissue that can be donated

Corneas, Heart valves, Skin, Bone, Tendons, Cartilage, Veins

Currently, there are over 113,000 people in the U.S. waiting for an organ transplant, of which 84 % are in need of kidneys.  Sadly, 22 people die every day waiting for an organ transplant that does not come in time. The prospect of an effective treatment for type 1 diabetes means hope for thousands of people living with the chronic condition.

Stem cell clinics make big claims but offer little evidence they can treat osteoarthritic knees

/ Kevin McCormack / 3 Comments

osteoarthritis knee

If someone says they have a success rate of close to 100 percent in treating a major health problem but offer little evidence to back that up, you might be excused for being more than a tad skeptical. And a new study says you would be right.

The health problem in question is osteoarthritis (OA) of the knee, something that affects almost 10 million Americans. It’s caused by the wearing down of the protective cartilage in the knee. That cartilage acts as a kind of shock absorber, so when it’s gone you have bone rubbing against bone. That’s not just painful but also debilitating, making it hard to lead an active life.

There is a lot of research taking place – including a clinical trial that CIRM is funding – that focuses on using stem cells to create new cartilage, but so far nothing has been approved by the US Food and Drug Administration for wider use. The reason for that is simple. No approach has yet proven it is both safe and effective.

No evidence? No worries

But that doesn’t stop many clinics around the US, and around the world, from claiming they have treatments that work and charging patients a hefty sum to get them.

In a study presented at the Annual Meeting of the American Academy of Orthopaedic Surgeons, researchers contacted 317 clinics in the US that directly market stem cell therapies to consumers. They asked the clinics for information on the cost of the procedure and their success rate.

  • Only 65 clinics responded
  • Lowest price was $1,150
  • Highest price was $12,000,
  • Average price of $5,156.

Only 36 clinics responded with information about success rates.

  • 10 claimed between 90 and 100 percent success
  • 15 claimed 80 to 90 percent success
  • 10 claimed 70 to 80 percent
  • One said just 55 percent.

None offered any evidence based on a clinical trial that supported those claims, and there was no connection between how much they charged and how successful they claimed to be.

In a news release about the study – which appears in the Journal of Knee Surgery – George Muschler, one of the lead authors, said that orthopedic surgeons have a duty to give patients the best information available about all treatment options.

“Recent systematic reviews of cellular therapies for the treatment of knee OA (over 400 papers screened) have found poor levels of evidence for the efficacy of these treatments to date. Current evidence does not justify the rapid rate of growth for these therapies.”

Nicolas Piuzzi, the other lead author on the study, says if the evidence doesn’t justify the growth in the number of clinics offering these therapies, it certainly doesn’t justify the prices they charge.

“The claim of “stem cell” therapy carries a high level of expectations for the potential benefits, but research is still many years away from providing clear evidence of effective treatment to patients. As clinicians and researchers, we have ethical, scientific, legal and regulatory concerns. Patients need to be aware of the status of research within the field. If they receive information from anyone offering a treatment claim of an 80 to 100 percent successful recovery, they should be concerned in observance of published peer-reviewed evidence.”

A shot in the arm for people with bad knees

/ Kevin McCormack / 4 Comments

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.

JointCartilege_nancy_liu-824x549

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.”

CIRM Board invests in three new stem cell clinical trials targeting arthritis, cancer and deadly infections

/ Kevin McCormack / 8 Comments

knee

Arthritis of the knee

Every day at CIRM we get calls from people looking for a stem cell therapy to help them fight a life-threatening or life-altering disease or condition. One of the most common calls is about osteoarthritis, a painful condition where the cartilage that helps cushion our joints is worn away, leaving bone to rub on bone. People call asking if we have something, anything, that might be able to help them. Now we do.

At yesterday’s CIRM Board meeting the Independent Citizens’ Oversight Committee or ICOC (the formal title of the Board) awarded almost $8.5 million to the California Institute for Biomedical Research (CALIBR) to test a drug that appears to help the body regenerate cartilage. In preclinical tests the drug, KA34, stimulated mesenchymal stem cells to turn into chondrocytes, the kind of cell found in healthy cartilage. It’s hoped these new cells will replace those killed off by osteoarthritis and repair the damage.

This is a Phase 1 clinical trial where the goal is primarily to make sure this approach is safe in patients. If the treatment also shows hints it’s working – and of course we hope it will – that’s a bonus which will need to be confirmed in later stage, and larger, clinical trials.

From a purely selfish perspective, it will be nice for us to be able to tell callers that we do have a clinical trial underway and are hopeful it could lead to an effective treatment. Right now the only alternatives for many patients are powerful opioids and pain killers, surgery, or turning to clinics that offer unproven stem cell therapies.

Targeting immune system cancer

The CIRM Board also awarded Poseida Therapeutics $19.8 million to target multiple myeloma, using the patient’s own genetically re-engineered stem cells. Multiple myeloma is caused when plasma cells, which are a type of white blood cell found in the bone marrow and are a key part of our immune system, turn cancerous and grow out of control.

As Dr. Maria Millan, CIRM’s President & CEO, said in a news release:

“Multiple myeloma disproportionately affects people over the age of 65 and African Americans, and it leads to progressive bone destruction, severe anemia, infectious complications and kidney and heart damage from abnormal proteins produced by the malignant plasma cells.  Less than half of patients with multiple myeloma live beyond 5 years. Poseida’s technology is seeking to destroy these cancerous myeloma cells with an immunotherapy approach that uses the patient’s own engineered immune system T cells to seek and destroy the myeloma cells.”

In a news release from Poseida, CEO Dr. Eric Ostertag, said the therapy – called P-BCMA-101 – holds a lot of promise:

“P-BCMA-101 is elegantly designed with several key characteristics, including an exceptionally high concentration of stem cell memory T cells which has the potential to significantly improve durability of response to treatment.”

Deadly infections

The third clinical trial funded by the Board yesterday also uses T cells. Researchers at Children’s Hospital of Los Angeles were awarded $4.8 million for a Phase 1 clinical trial targeting potentially deadly infections in people who have a weakened immune system.

Viruses such as cytomegalovirus, Epstein-Barr, and adenovirus are commonly found in all of us, but our bodies are usually able to easily fight them off. However, patients with weakened immune systems resulting from chemotherapy, bone marrow or cord blood transplant often lack that ability to combat these viruses and it can prove fatal.

The researchers are taking T cells from healthy donors that have been genetically matched to the patient’s immune system and engineered to fight these viruses. The cells are then transplanted into the patient and will hopefully help boost their immune system’s ability to fight the virus and provide long-term protection.

Whenever you can tell someone who calls you, desperately looking for help, that you have something that might be able to help them, you can hear the relief on the other end of the line. Of course, we explain that these are only early-stage clinical trials and that we don’t know if they’ll work. But for someone who up until that point felt they had no options and, often, no hope, it’s welcome and encouraging news that progress is being made.

 

 

Translating great stem cell ideas into effective therapies

/ Kevin McCormack / Leave a comment

alzheimers

CIRM funds research trying to solve the Alzheimer’s puzzle

In science, there are a lot of terms that could easily mystify people without a research background; “translational” is not one of them. Translational research simply means to take findings from basic research and advance them into something that is ready to be tested in people in a clinical trial.

Yesterday our Governing Board approved $15 million in funding for four projects as part of our Translational Awards program, giving them the funding and support that we hope will ultimately result in them being tested in people.

Those projects use a variety of different approaches in tackling some very different diseases. For example, researchers at the Gladstone Institutes in San Francisco received $5.9 million to develop a new way to help the more than five million Americans battling Alzheimer’s disease. They want to generate brain cells to replace those damaged by Alzheimer’s, using induced pluripotent stem cells (iPSCs) – an adult cell that has been changed or reprogrammed so that it can then be changed into virtually any other cell in the body.

CIRM’s mission is to accelerate stem cell treatments to patients with unmet medical needs and Alzheimer’s – which has no cure and no effective long-term treatments – clearly represents an unmet medical need.

Another project approved by the Board is run by a team at Children’s Hospital Oakland Research Institute (CHORI). They got almost $4.5 million for their research helping people with sickle cell anemia, an inherited blood disorder that causes intense pain, and can result in strokes and organ damage. Sickle cell affects around 100,000 people in the US, mostly African Americans.

The CHORI team wants to use a new gene-editing tool called CRISPR-Cas9 to develop a method of editing the defective gene that causes Sickle Cell, creating a healthy, sickle-free blood supply for patients.

Right now, the only effective long-term treatment for sickle cell disease is a bone marrow transplant, but that requires a patient to have a matched donor – something that is hard to find. Even with a perfect donor the procedure can be risky, carrying with it potentially life-threatening complications. Using the patient’s own blood stem cells to create a therapy would remove those complications and even make it possible to talk about curing the disease.

While damaged cartilage isn’t life-threatening it does have huge quality of life implications for millions of people. Untreated cartilage damage can, over time lead to the degeneration of the joint, arthritis and chronic pain. Researchers at the University of Southern California (USC) were awarded $2.5 million to develop an off-the-shelf stem cell product that could be used to repair the damage.

The fourth and final award ($2.09 million) went to Ankasa Regenerative Therapeutics, which hopes to create a stem cell therapy for osteonecrosis. This is a painful, progressive disease caused by insufficient blood flow to the bones. Eventually the bones start to rot and die.

As Jonathan Thomas, Chair of the CIRM Board, said in a news release, we are hoping this is just the next step for these programs on their way to helping patients:

“These Translational Awards highlight our goal of creating a pipeline of projects, moving through different stages of research with an ultimate goal of a successful treatment. We are hopeful these projects will be able to use our newly created Stem Cell Center to speed up their progress and pave the way for approval by the FDA for a clinical trial in the next few years.”

Finally a possible use for your excess fat; using it to fix your arthritic knee

/ Kevin McCormack / Leave a comment

shutterstock_425039020

One of the most common questions we get asked at CIRM, almost every other day to be honest, is “are there any stem cell treatments for people with arthritis in their knees?” It’s not surprising. This is a problem that plagues millions of Americans and is one of the leading causes of disability in the US.

Sadly, we have to tell people that there are no stem cell treatments for osteoarthritis (OA) in the knee that have been approved by the Food and Drug Administration (FDA). There’s also a lack of solid evidence from clinical trials that the various approaches are effective.

But that could be changing. There’s a growing number of clinical trials underway looking at different approaches to treating OA in the knee using various forms of stem cells. Sixteen of those are listed at clinicaltrials.gov. And one new study suggests that just one injection of stem cells may be able to help reduce pain and inflammation in arthritic knees, at least for six months. The operative word here being may.

The study, published in the journal Stem Cells Translational Medicine,  used adipose-derived stromal cells, a kind of stem cell taken from the patient’s own fat. Previous studies have shown that these cells can have immune boosting and anti-scarring properties.

The cells were removed by liposuction, so not only did the patient’s get a boost for their knees they also got a little fat reduction. A nice bonus if desired.

The study was quite small. It involved 18 patients, between the ages of 50 and 75, all of whom had suffered from osteoarthritis (OA) in the knee for at least a year before the treatment. This condition is caused by the cartilage in the knee breaking down, allowing bones to rub against each other, leading to pain, stiffness and swelling.

One group of patients were given a low dose of the cells (23,000) injected directly into the knee, one a medium dose (103,000) and one a high dose (503,000).

Over the next six months, the patients were closely followed to see if there were any side effects and, of course, any improvement in their condition. In a news release, Christian Jorgensen, of University Hospital of Montpellier, the director of the study, said the results were encouraging:

“Although this phase I study included a limited number of patients without a placebo arm we were able to show that this innovative treatment was well tolerated in patients with knee OA and it provided encouraging preliminary evidence of efficacy. Interestingly, patients treated with low-dose ASCs significantly improved in pain and function compared with the baseline.”

The researchers caution that the treatment doesn’t halt the progression of OA and does not restore the damaged cartilage, instead it seems to help patients by reducing inflammation.

In a news article about the study Tony Atala, director of the Wake Forest Institute for Regenerative Medicine, in Winston-Salem, N.C. and the editor of Stem Cells Translational Medicine said the study offered the patients involved another benefit:

“In fact, most of the patients (in the study group) who had previously scheduled total knee replacement surgery decided to cancel the surgery. It will be interesting to see if these improvements are seen in larger groups of study participants.”

Interesting is an understatement.

But while this is encouraging it’s important to remember it was done in a small group of patients and needs to be replicated in a much larger group before we can draw any solid conclusions. It will also be important to see if the benefits last longer than six months.

We might not have to wait too long for some answers. The researchers are already running a 2-year trial involving 150 people in Europe.

We’ll let you know what they find.

 

These Are the Cells You’re Looking for: Scientists Devise New Way to Extract Bone-Making Stem Cells from Fat

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Buried within our fat tissue are stashes of stem cells—a hidden reservoir of cells that, if given the right cues, can transform into cells that make up bone, cartilage or fat. These cells therefore represent a much-needed store for regenerative therapies that rebuild bone or cartilage lost to disease or injury.

Finding cells that have bone-making potential is more efficiently done by looking at the genes they express (in this case, ALPL) than at proteins on their surface. The bone matrix being produced by cells is stained red in samples of cells that do not express ALPL (left), those that do express ALPL (right). [Credit: Darling lab/Brown University]

Finding cells that have bone-making potential is more efficiently done by looking at the genes they express (in this case, ALPL) than at proteins on their surface. The bone matrix being produced by cells is stained red in samples of cells that do not express ALPL (left), those that do express ALPL (right). The center image shows both types of cells prior to sorting [Credit: Darling lab/Brown University]

The only problem with these tucked-away cellular reservoirs, however, is identifying them and getting them out.

But now, researchers at Brown University have devised a unique method of identifying, extracting and then cultivating these bone-producing stem cells. Their results, published today in the journal Stem Cell Research & Therapy, seem to offer a much-needed alternative resource for growing bone.

Traditional methods attempting to locate and extract these stem cells focused on proteins that reside on the surface of the cells. Find the proteins, scientists reasoned, and you’ve found the cell.

Unfortunately, that method was not fool proof, and many argued that it wasn’t finding all the cells that reside in the fat tissue. So Brown scientists, led by Dr. Eric Darling found an alternative.

They knew that a gene called ALPL is an indicator of bone-making cells. If the gene is switched on, the cell has the potential to make bone. If it’s switched off, it does not. So Darling and his team devised a fluorescent marker, or tag, that stuck to the cells with activated ALPL. They then used a special machine to sort the cells: those that glowed went into one bucket, those that did not went into the other.

To prove that these ALPL-activated cells were indeed capable of becoming bone and cartilage, they then cultivated them for several weeks in a petri dish. Not only did they transform into the right cell types—they did so in greater numbers than cells extracted using traditional methods.

Hetal Marble, a graduate student in Darling’s lab and the paper’s first author, argues that tagging genes—rather than surface proteins—in order to distinguish and weed out cell types represents an important paradigm shift in the field. As he stated in a press release:

“Approaches like this allow us to isolate all the cells that are capable of doing what we want, whether they fit the archetype of what a stem cell is or is not. The paradigm shift is thinking about isolating populations that are able to achieve an end point rather than isolating populations that fit a strictly defined archetype.”

While their method is both precise and accurate, there is one drawback: it is slow.

Currently, it takes four days to tag, extract and cultivate the bone-making cells. In the future, the team hopes they can shorten this time frame so that they could perform the required steps within a single surgical session. As Darling stated:

“If you can take a patient into the OR, isolate a bunch of their cells, sort them and put them back in—that’s ideally where we’d like to go with this.”