When a doctor gives you a medication you like to think that it’s safe, that it has been tested to make sure it will do you some good or, at the very least, won’t do you any harm. That’s particularly true when the patient is a pregnant woman. You hope the medication won’t harm her or her unborn child. Now scientists in Switzerland have found a new way to do that that is faster and easier than previous methods, and it uses cell cultures instead of animals.
Right now, drugs that are intended for use in pregnant women
have to undergo some pretty rigorous testing before they are approved. This
involves lots of tests in the lab, and then in animals such as rats and
rabbits. It’s time consuming, costly, and not always accurate because animals
never quite mimic what happens in people.
In the past researchers tested new
medications in the lab on so-called “embryoid bodies”. These are
three-dimensional clumps of cells developed from embryonic stem cells from mice.
The problem is that even when tested in this way the cells don’t always reflect
what happens to a medication as it passes through the body. For example, some
medications can seem fine on the surface but after they pass through the liver
can take on toxic qualities.
So, scientists at ETH Zurich in Basel,
Switzerland, developed a better way to test for toxicity.
They took a cell-culture chip and created several
compartments on it, in some they placed the embryoid bodies and in others they
put microtissue samples from human livers.
The different compartments were connected so that fluid flowed freely
from the embryoid bodies to the liver and vice versa.
In a news
release, Julia Boos, a lead author of the study, says this better reflects
what happens to a medication exposed to a human metabolism.
“We’re the first
to directly combine liver and embryonic cells in a body-on-a-chip approach. Metabolites
created by the liver cells – including metabolites that are stable for just a
few minutes – can thus act directly on the embryonic cells. In contrast to
tests on mice, in our test, the substances are metabolised by human liver cells
– in other words, just as they would be in the human body when the medication
To see if this
worked in practice the researchers tested their approach on the chemotherapy
drug cyclophosphamide, which is turned into a toxic substance after passing
through the liver.
results from testing cyclophosphamide with the new liver/embryoid body method
to the older method. They found the new approach was far more sensitive and
determined that a 400 percent lower concentration of cyclophosphamide was
enough to pose a toxic threat.
The team now hope to refine the test even further so it can
one day, hopefully, be applied to drug development on a large scale.
Understanding the basic biology of how a cell functions can be crucial to being able to better understand a disease and unlock a potential approach for a treatment. Stem cells are unique in that they give scientists the opportunity to create a controlled environment of cells that might be otherwise difficult to study. Dr. Eva Hedlund and a team of researchers at the Karolinska Institute in Sweden utilize a stem cell model approach to uncover findings related to Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s Disease.
ALS is a progressive neurodegenerative disease that destroys motor neurons, a type of nerve cell, that are important for voluntary muscle movement. When motor neurons can no longer send signals to the muscles, the muscles begin to deteriorate, a process formally known as atrophy. The progressive atrophy leads to muscle paralysis, including those in the legs and feet, arms and hands, and those that control swallowing and breathing. It affects about 30,000 people in the United States alone, with 5,000 new cases diagnosed each year. There is currently no cure.
In a previous study, researchers at the Karolinska Institute were able to successfully create oculomotor neurons from embryonic stem cells. For reasons not yet fully understood, oculomotor neurons are “ALS resilient” and can survive all stages of the disease.
In the current study, published in Stem Cell Reports, Dr. Hedlund and her team found that the oculomotor neurons they generated appeared more resilient to ALS-like degeneration when compared to spinal cord motor neurons, something commonly observed in humans. Furthermore, they discovered that their “ALS resilient” neurons generated from stem cells activate a survival-enhancing signal known as Akt, which is common in oculomotor neurons in humans and could explain their resilience. These results could potentially aid in identifying genetic targets for treatments protecting sensitive neurons from the disease.
The beginning of a clinical trial, particularly the first time a new therapy is being tested in people, is often a time of equal parts anticipation and nervousness. Anticipation, because you have been working to this point for many years. Nervousness, because you have never tested this in people before and even though you have done years of study to show it is probably safe, until you try it in people you never really know.
That’s why the latest results from the CIRM-funded SCiStar Study, a clinical trial for spinal cord injury, are so encouraging. The results show that, one year after being treated, all the patients are doing well, none have experienced any serious side effects, and most have experienced impressive gains in movement, mobility and strength.
In a news release Ed Wirth, BioTIme’s Chief Medical Officer, said they were encouraged by what they saw:
“We believe the primary goals of the SCiStar Study, which
were to observe the safety of OPC1 in cervical spinal cord injury patients as
well as other important metrics including related to the optimal timing of OPC1
injection, tolerability of the immunosuppression regimen, engraftment of OPC1
cells, and rates of motor recovery observed among different study
subpopulations, have all been successfully achieved.”
The study involved
transplanting what the researchers called AST-OPC1
cells into patients who have suffered recent injuries that have left them
paralyzed from the neck down. AST-OPC1 are oligodendrocyte progenitor
cells, which develop into cells that support and protect nerve cells in the
central nervous system, the area damaged in spinal cord injury. It’s hoped the
treatment will restore connections at the injury site, allowing patients to
regain some movement and feeling.
Altogether 25 patients were involved. Three, in Cohort 1, were given injections of just two million OPC1 cells. This was to ensure the approach was safe and wouldn’t endanger patients. The remaining 22, in Cohorts 2-5, were given between 10 and 20 million cells. One year after the last patient was treated the results show:
MRI scans show no evidence of adverse changes in any of the 25 SCiStar study subjects.
No SCiStar study subjects had worsening of neurological function post-injection
At 12 months, 95% (21/22) of patients in Cohorts 2-5 recovered at least one motor level on at least one side and 32% (7/22) of these subjects recovered two or more motor levels on at least one side.
No patient saw decreased motor function following administration of OPC1 and all either retained for 12 months the motor function recovery seen through 6 months or experienced further motor function recovery from 6 to 12 months.
All three subjects in Cohort 1 and 95% (21/22) of those in Cohorts 2 to 5 have MRI scans at 12 months consistent with the formation of a tissue matrix at the injury site. This is encouraging evidence the OPC1 cells have engrafted at the injury site and helped to prevent cavitation, a destructive process that occurs within the spinal cord following spinal cord injuries, and typically results in permanent loss of motor and sensory function.
“We appreciate the support of the California Institute for
Regenerative Medicine, the world’s largest institution dedicated to bringing
the future of cellular medicine closer to reality, whose generous grant funding
to date of $14.3 million has helped advance the clinical development of our
OPC1 program and generate these encouraging clinical results in patients with
traumatic spinal cord injuries.”
is now planning to meet with the Food and Drug Administration (FDA) later this
year to discuss next steps for the therapy. Soon as we know the outcome of
those talks, we’ll share them with you.
For patients battling cancer for the first time, it can be quite a draining and grueling process. Many treatments are successful and patients go into remission. However, there are instances where the cancer returns in a much more aggressive form. Unfortunately, this was the case for Derek Ruff.
After being in remission for ten years, Derek’s cancer returned as Stage IV colon cancer, meaning that the cancer has spread from the colon to distant organs and tissues. According to statistics from Fight Colorectal Cancer, colorectal cancer is the 2nd leading cause of cancer death among men and women combined in the United States. 1 in 20 people will be diagnosed with colorectal cancer in their lifetime and it is estimated that there will be 140,250 new cases in 2019 alone. Fortunately, Derek was able to enroll in a groundbreaking clinical trial to combat his cancer.
In February 2019, as part of a clinical trial at the Moores Cancer Center at UC San Diego Health in collaboration with Fate Therapeutics, Derek became the first patient in the world to be treated for cancer with human-induced pluripotent stem cells (hiPSCs). hiPSCs are human adult cells, such as those found on the skin, that are reprogrammed into stem cells with the ability to turn into virtually any kind of cell. In this trial, hiPSCs were reprogrammed into natural killer (NK) cells, which are specialized immune cells that are very effective at killing cancer cells, and are aimed at treating Derek’s colon cancer.
A video clip from ABC 10 News San Diego features an interview with Derek and the groundbreaking work being done.
In a public release, Dr. Dan Kaufman, one of the lead investigators of this trial at UC San Diego School of Medicine, was quoted as saying,
“This is a landmark accomplishment for the field of stem cell-based medicine and cancer immunotherapy. This clinical trial represents the first use of cells produced from human induced pluripotent stem cells to better treat and fight cancer.”
In the past, CIRM has given Dr. Kaufman funding related to the development of NK cells. One was a $1.9 million grant for developing a different type of NK cell from hiPSCs, which could also potentially treat patients with lethal cancers. The second grant was a $4.7 million grant for developing NK cells from human embryonic stem cells (hESCs) to potentially treat patients with acute myelogenous leukemia (AML).
In the public release, Dr. Kaufman is also quoted as saying,
“This is a culmination of 15 years of work. My lab was the first to produce natural killer cells from human pluripotent stem cells. Together with Fate Therapeutics, we’ve been able to show in preclinical research that this new strategy to produce pluripotent stem cell-derived natural killer cells can effectively kill cancer cells in cell culture and in mouse models.”
Don Reed has been a champion of CIRM even before there was a CIRM. He’s a pioneer in pushing for funding for stem cell research and now he’s working hard to raise awareness about the difference that funding is making.
In a recent article on Daily Kos, Don highlighted one of the less celebrated partners in this research, the humble rat.
A BETTER RAT? Benefit #62 of the California Stem Cell Agency
By Don C. Reed
When I told my wife Gloria I was writing an article about rats, she had several comments, including: “Oo, ugh!” and also “That’s disgusting!”
Obviously, there are problems with rats, such as
when they chew through electrical wires, which may cause a short circuit
and burn down the house. Also, they are blamed for carrying diseased
fleas in their ears and spreading the Black Plague, which in 1340 killed
half of China and one-third of Europe—but this is not certain. The
plague may in fact have been transmitted by human-carried parasites.
But there are positive aspects to rats as well. For
instance: “…a rat paired with another that has a disability…will be
very kind to the other rat. Usually, help is offered with food,
cleaning, and general care.”—GUIDE TO THE RAT, by Ginger Cardinal.
Above all, anyone who has ever been sick owes a
debt to rats, specifically the Norway rat with that spectacular name,
rattus norvegicus domesticus, found in labs around the world.
I first realized its importance on March 1, 2002,
when I held in my hand a rat which had been paralyzed, but then
recovered the use of its limbs.
The rat’s name was Fighter, and she had been given a derivative of embryonic stem cells, which restored function to her limbs. (This was the famous stem cell therapy begun by Hans Keirstead with a Roman Reed grant, developed by Geron, and later by CIRM and Asterias, which later benefited humans.)
As I felt the tiny muscles struggling to be free,
it was like touching tomorrow— while my paralyzed son, Roman Reed, sat
in his wheelchair just a few feet away.
Was it different working with rats instead of mice? I had heard that the far smaller lab mice were more “bitey” than rats.
Wanting to know more about the possibilities of a “better rat”, I went to the CIRM website, (www.cirm.ca.gov) hunted up the “Tools and Technology III” section, and the following complicated sentence::
“Embryonic stem cell- based generation of rat models for assessing human cellular therapies.”
Hmm. With science writing, it always takes me a
couple of readings to know what they were talking about. But I
recognized some of the words, so that was a start.
“Stemcells… rat models… human therapies….”
I called up Dr. Qilong Ying, Principle Investigator (PI) of the study.
As he began to talk, I felt a “click” of recognition, as if, like pieces of a puzzle, facts were fitting together.
It reminded me of Jacques Cousteau, the great
underwater explorer, when he tried to invent a way to breathe
underwater. He had the compressed air tank, and a mouthpiece that would
release air—but it came in a rush, not normal breathing.
So he visited his friend, race car mechanic Emil
Gagnan, and told him, “I need something that will give me air, but only
when I inhale,”– and Gagnan said: “Like that?” and pointed to a metal
contraption on a nearby table.
It was something invented for cars. But by adding
it to what Cousteau already had, the Cousteau-Gagnan SCUBA (Self
Contained Underwater Breathing Apparatus) gear was born—and the ocean
could now be explored.
Qi-Long Ying’s contribution to science may also be a piece of the puzzle of cure…
A long-term collaboration with Dr. Austin Smith centered on an attempt to do with rats what had done with mice.
In 2007, the Nobel Prize in Medicine had been won by Dr. Martin Evans, Mario Capecchi, and Oliver Smithies. Working independently, they developed “knock-out” and “knock-in” mice, meaning to take out a gene, or put one in.
But could they do the same with rats?
“We and others worked very, very hard, and got nowhere,” said Dr. Evans.
Why was this important?
Many human diseases cannot be mimicked in the
mouse—but might be in the rat. This is for several reasons: the rat is
about ten times larger; its internal workings are closer to those of a
human; and the rat is considered several million years closer (in
evolutionary terms) to humans than the mouse.
In 2008 (“in China, that is the year of the rat,” noted Dr. Ying in our conversation) he received the first of three grants from CIRM.
“We proposed to use the classical embryonic stem
cell-based gene-targeting technology to generate rat models mimicking
human heart failure, diabetes and neurodegenerative diseases…”
How did he do?
In 2010, Science Magazine honored him with
inclusion in their “Top 10 Breakthroughs for using embryonic stem
cell-based gene targeting to produce the world’s first knockout rats,
modified to lack one or more genes…”
And in 2016, he and Dr. Smith received the McEwen Award for Innovation, the highest honor bestowed by the International Society for Stem Cell Research (ISSCR).
Using knowledge learned from the new (and more
relevant to humans) lab rat, it may be possible to develop methods for
the expansion of stem cells directly inside the patient’s own bone
marrow. Stem cells derived in this fashion would be far less likely to
be rejected by the patient. To paraphrase Abraham Lincoln, they would
be “of the patient, by the patient and for the patient—and shall not
perish from the patient”—sorry!
Several of the rats generated in Ying’s lab (to mimic human diseases) were so successful that they have been donated to the Rat Research Resource center so that other scientists can use them for their study.
“Maybe in the future we will develop a cure for some diseases because of knowledge from using rat models,” said Ying. “I think it’s very possible. So we want more researchers from USC and beyond to come and use this technology.”
Last week’s news headlines were dominated by one big story, the use of a stem cell transplant to effectively cure a person of HIV. But there were other stories that, while not quite as striking, did also highlight how the field is advancing.
A new way to boost brain cells
It’s hard to fix
something if you don’t really know what’s wrong in the first place. It would be
like trying to determine why a car is not working just by looking at the hood
and not looking inside at the engine. The human brain is far more complex than
a car so trying to determine what’s going wrong is infinitely more challenging.
But a new study could help give us a new option.
Luxembourg and Germany have developed a new computer model for what’s happening
inside the brain, identifying what cells are not operating properly, and fixing
Antonio del Sol, one
of the lead authors of the study – published in the journal Cell
– says their new model allows them to identify which stem cells are active and
ready to divide, or dormant.
“Our results constitute an important
step towards the implementation of stem cell-based therapies, for instance for
neurodegenerative diseases. We were able to show that, with computational
models, it is possible to identify the essential features that are
characteristic of a specific state of stem cells.”
The work, done in
mice, identified a protein that helped keep brain stem cells inactive in older
animals. By blocking this protein they were able to help “wake up” those stem
cells so they could divide and proliferate and help regenerate the aging brain.
And if it works in
mice it must work in people right? Well, that’s what they hope to see next.
Deeper understanding of fetal development
According to the Mayo
Clinic between 10 and 20 percent of known pregnancies end in
miscarriage (though they admit the real number may be even higher) and our lack
of understanding of fetal development makes it hard to understand why. A new
study reveals a previously unknown step in this development that could help
provide some answers and, hopefully, lead to ways to prevent miscarriages.
Researchers at the
Karolinska Institute in Sweden used genetic sequencing to follow the
development stages of mice embryos. By sorting those different sequences into a
kind of blueprint for what’s happening at every stage of development they were
able to identify a previously unknown phase. It’s the time between when the
embryo attaches to the uterus and when it begins to turn these embryonic stem
cells into identifiable parts of the body.
Lead researcher Qiaolin Deng says this finding provides vital new evidence.
“Being able to follow the
differentiation process of every cell is the Holy Grail of developmental
biology. Knowledge of the events and factors that govern the development of the
early embryo is indispensable for understanding miscarriages and congenital
disease. Around three in every 100 babies are born with fetal malformation
caused by faulty cellular differentiation.”
Could a new drug discovery
reduce damage from a heart attack?
Every 40 seconds someone in the US has a heart attack. For many it is fatal but even for those who survive it can lead to long-term damage to the heart that ultimately leads to heart failure. Now British researchers think they may have found a way to reduce that likelihood.
Using stem cells to
create human heart muscle tissue in the lab, they identified a protein that is
activated after a heart attack or when exposed to stress chemicals. They then
identified a drug that can block that protein and, when tested in mice that had
experienced a heart attack, they found it could reduce damage to the heart
muscle by around 60 percent.
Prof Michael Schneider,
the lead researcher on the study, published in Cell
Stem Cell, said this could be a game changer.
“There are no
existing therapies that directly address the problem of muscle cell death and
this would be a revolution in the treatment of heart attacks. One reason why
many heart drugs have failed in clinical trials may be that they have not been
tested in human cells before the clinic. Using both human cells and animals
allows us to be more confident about the molecules we take forward.”
Can cell therapy beat the most difficult diseases?
the question posed in a headline in National
Geographic. The answer; maybe, but it is going to take time and
article focuses on the use of iPS cells, the man-made equivalent of embryonic
stem cells that can be turned into any kind of cell or tissue in the body. The
reporter interviews Kemal
Malik, the member of the Board of Management for pharmaceutical giant Bayer who
is responsible for innovation. When it comes to iPS cells, it’s clear Malik is
a true believer in their potential.
“Because every cell
in our bodies can be produced from a stem cell, the applicability of cell
therapy is vast. iPSC technology has the potential to tackle some of the most
challenging diseases on the planet.”
he also acknowledges that the field faces some daunting challenges, including:
How to manufacture
the cells on a large scale without sacrificing quality and purity
How do you create
products that have a stable shelf life and can be stored until needed?
How do you handle
immune reactions if you are giving these cells to patients?
Malik remains confident we can overcome those challenges and realize the full
potential of these cells.
“I believe human
beings are on the cusp of the next big wave of pharmaceutical innovation. The
use of living cells to make people better.”
if to prove Malik right there was also news this week that researchers at
Japan’s Keio University have been given permission to start a clinical trial
using iPS cells to treat people with spinal cord injuries. This would be the
first of its kind anywhere in the world.
Japan launches iPSC clinical trial for spinal cord injury
article in Biospace
says that the researchers plan to treat four patients who have suffered varying
degrees of paralysis due to a spinal cord injury. They will take cells from the patients and,
using the iPS method, turn them into the kind of nerve cells found in the
spinal cord, and then transplant two million of them back into the patient. The
hope is that this will create new connections that restore movement and feeling
in the individuals.
trial is expected to start sometime this summer.
has already funded a first-of-its-kind clinical trial for spinal cord injury
Biotherapeutics. That clinical trial used embryonic stem cells
turned into oligodendrocyte progenitor cells – which develop into cells that support
and protect nerve cells in the central nervous system. We blogged about the
encouraging results from that trial here.
High fat diet drives
Finally today, researchers at Salk have uncovered a possible cause to the rise in colorectal cancer deaths among people under the age of 55; eating too much high fat food.
digestive system works hard to break down the foods we eat and one way it does
that is by using bile acids. Those acids don’t just break down the food,
however, they also break down the lining of our intestines. Fortunately, our
gut has a steady supply of stem cells that can repair and replace that lining.
Unfortunately, at least according to the team from Salk, mutations in these
stem cells can lead to colorectal cancer.
study, published in the journal Cell,
shows that bile acids affect a protein called FXR that is responsible for
ensuring that gut stem cells produce a steady supply of new lining for the gut
wall. When someone eats a high fat diet it upsets the balance of bile acids,
starting a cascade of events that help cancer develop and grow.
release Annette Atkins, a co-author of the study, says there is a
strong connection between bile acid and cancer growth:
“We knew that
high-fat diets and bile acids were both risk factors for cancer, but we weren’t
expecting to find they were both affecting FXR in intestinal stem cells.”
next time you are thinking about having that double bacon cheese burger for
lunch, you might go for the salad instead. Your gut will thank you. And it
might just save your life.
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.”
ViaCyte, a company that CIRM has supported for many years, has announced international expansion of a clinical trial to test their therapeutic PEC-Direct product in patients with Type I Diabetes.
The first European patient in Brussels was implanted with the PEC-Direct product candidate that, in animal models, is able to form functional beta cells. Patients with Type I Diabetes are unable to control blood glucose levels because their immune system attacks insulin-producing beta cells, which are responsible for regulating blood sugar.
ViaCyte PEC-Direct product candidate
The hope is that PEC-Direct would eliminate the need for patients to take daily doses of insulin, the current treatment standard to prevent the side effects of high blood glucose levels, such as heart disease, kidney damage and nerve damage.
The PEC-Direct product is implanted under the skin. The progenitor cells inside it are designed to mature in to human pancreatic islet cells, including glucose-responsive insulin-secreting beta cells, following implant. These are the cells destroyed by Type 1 Diabetes
In this first phase of the clinical trial, patients are administered a subtherapeutic dose of the drug to ensure that that the implants are able to generate beta cells in the body. The next part of the trial will determine whether or not the formed beta cells are able to produce appropriate levels of insulin and modulate blood glucose levels. A sister trial is currently underway in North America as well. This work is a collaboration between ViaCyte and The Center for Beta Cell Therapy in Diabetes.
CIRM is proud to be a supporter of companies such as ViaCyte that are conducting groundbreaking research to make stem cell therapy an effective and realistic treatment option for many different diseases.
Currently, there is nothing that completely reverses SCI damage and most treatment is aimed at rehabilitation and empowering patients to lead as normal a life as possible under the circumstances. Improved treatment options are necessary both to improve patients’ overall quality of life, and to reduce associated healthcare costs.
Scientists at UC San Diego’s School of Medicine and Institute of Engineering in Medicine have made critical progress in providing SCI patients with hope towards a more comprehensive and longer lasting treatment option.
Prof. Shaochen Chen and his 3D printer
In a study partially funded by CIRM and published in Nature Medicine, Dr. Mark Tuszynski’s and Dr. Shaochen Chen’s groups used a novel 3D printing method to grow a spinal cord in the lab.
Previous studies have seen some success in lab grown neurons or nerve cells, improving SCI in animal models. This new study, however, is innovative both for the speed at which the neurons are printed, and the extent of the neuronal network that is produced.
To achieve this goal, the scientists used a biological scaffold that directs the growth of the neurons so they grow to the correct length and generate a complete neuronal network. Excitingly, their 3D printing technology was so efficient that they were able to grow implants for an animal model in 1.6 seconds, and a human-sized implant in just ten minutes, showing that their technology is scalable for injuries of different sizes.
When they tested the spinal cord implants in rats, they found that not only did the implant repair the damaged spinal cord tissue, but it also provided sustained improvement in motor function up to six months after implantation.
Just as importantly, they also observed that blood vessels had infiltrated the implanted tissue. The absence of vascularized tissue is one of the main reasons engineered implants do not last long in the host, because blood vessels are necessary to provide nutrients and support tissue growth. In this case, the animal’s body solved the problem on its own.
In a press release, one of the co-first authors of the paper, Dr. Kobi Koffler, states the importance and novelty of this work:
“This marks another key step toward conducting clinical trials to repair spinal cord injuries in people. The scaffolding provides a stable, physical structure that supports consistent engraftment and survival of neural stem cells. It seems to shield grafted stem cells from the often toxic, inflammatory environment of a spinal cord injury and helps guide axons through the lesion site completely.”
In order to make this technology viable for human clinical trials, the scientists are testing their technology in larger animal models before moving into humans, as well as investigating how to improve the longevity of the neuronal network by introducing proteins into the scaffolds.