The first ever in utero stem cell treatment for spina bifida is the culmination of decades of work from UC Davis surgeon-scientist Diana Farmer. This novel fetal surgery at UC Davis Children’s Hospital could change the life of a developing baby with spina bifida, who otherwise could be born paralyzed from the waist down. This original documentary from UC Davis Health explores the science behind the procedure and chronicles the journey of the first mother to participate in the groundbreaking CuRe Trial.
[NARRATOR] The surgery center at UC Davis Children’s Hospital sees about 5,000 surgeries per year, but never one quite like today’s. This procedure is the first of its kind in the world. You can’t tell at first glance, but there are two patients on this operating table – a pregnant woman and the developing baby inside of her. It’s the first ever in utero stem cell treatment for spinal bifida, a culmination of decades of work for UC Davis surgeon-scientist Diana Farmer. Farmer is leading the world’s first human clinical trial using stem cells to treat spina bifida before birth by surgically applying the cells to the spinal cord in a still developing fetus.
Spina bifida occurs when a fetus’s spinal tissue doesn’t close properly. It leaves the spinal cord dangerously exposed. The Spinal Bifida Association estimates there are more than 70,000 people with the condition in the U.S..
Surgeons can perform fetal surgery and close a fetus’s open spinal cord.
It can stop spina bifida from becoming more severe. But in many cases, the patient is still left with some abnormal functions, such as paralysis. Farmer wants to take the next step: to reverse spina bifida and even cure it. [FARMER] I had this idea that stem cells might improve this.
If we could somehow apply stem cells, give stem cells to the spinal cord, that not only would we protect future injury that we were doing with the closing the back in utero, but we could reverse the damage that had already occurred.
[NARRATOR] The name of the trial is [NARRATOR]Cellular Therapy for In Utero Repair of Myelomeningocele, which gets abbreviated to “CuRe.” The CuRe Trial team has FDA approval to begin enrolling human patients and the California Institute for Regenerative Medicine gave them a $9 million grant to do the work. [FARMER] I’ve been working toward this day when we’re treating patients with stem cells for spinal bifida for almost 25 years now. Stem cells have shown promise in treating many conditions before birth.
[NARRATOR] This leading pediatric and fetal surgeon began her spinal bifida work at UC San Francisco and brought it with her when she moved to UC Davis. She also brought along a bright, young postdoctoral researcher she met at Berkeley in 2009. [WANG] When I first started as an engineer, I was always thinking about how to apply new technologies into real life patient care, how to help patients with what we know about and what we develop in the lab.
This is what we’re doing right now. The CuRe Trial has been a massive team effort.
There are more than 40 people in this lab. Over the past decade, Wang estimates, more than 100 people have been involved, including lab supervisor Chris Pavetti. [PAVETTI] I really like the idea of helping kids, so the idea of working on something that could impact a child’s life was really appealing to me. [NARRATOR] The academic health system at UC Davis is uniquely suited for this trial, thanks to its stem cell research program, biomedical engineering expertise and world famous veterinary school and large animal lab. For the in utero stem cell treatment, researchers needed to determine what kind of animal model and what kind of cells to use.
[PAVETTI] We hadn’t even decided what stem cell we wanted to use yet, so it was trial and error really. [FARMER] We tried IPS cells, we tried nanofiber scaffolds. We tried all kinds of solutions, all kinds of things that didn’t work. So every story of success, if you peel back the onion, has several stories of failure. But we never gave up.
[NARRATOR] They found what was needed in what are called mesenchymal stem cells from the placenta.
Researchers believe these cells pose fewer complications than embryonic stem cells. [FARMER] I think of it as delivering their magic stem cell juice and then go away once they’ve done their job. [NARRATOR] The cells are placed on a material that mimics the spinal cord’s outer membrane called the dura. [FARMER] We seeded the cells on an already FDA approved dural patch used for brain tumors and things, so that made it easier from an FDA hurdle point of view and it turns out the cells loved it.
[NARRATOR] The next step, the sheep trial. In 2015, stem cells were applied to the spinal cords of lambs that would have been born unable to stand or walk. [PIVETTI] The lamb that was treated without stem cells cannot get up. It has complete hind limb paralysis, whereas the sibling to that limb is actually able to stand up and walk around pretty much like a normal lamb. [WANG] They were able to stand at birth and they were able to run around almost normally.
It was amazing. [PIVETTI] We were in shock. It gave us hope that, you know, maybe this could work as a therapy for these kids. [NARRATOR] As further proof that the idea might really work, researchers tried a similar treatment for these bulldog puppies. Darla and Spanky were born with naturally occurring spina bifida.
UC Davis medical and veterinary experts surgically applied stem cells to the puppy spines when they were ten weeks old. Within months, Darla and Spanky were running, jumping, playing. Wang says the result shows the power of these uniquely engineered stem cells. [WANG] Stem cells are very smart, actually.
When you culture stem cells in different environments, they’re going to do different things.
They’re going to respond to the culture media. You know, they’re going to be induced to do the things that they think they should do. [NARRATOR] With FDA approval of the cell safety profile in animal models, the search for the first human patients begins. The search for the first baby in the world to receive this groundbreaking, potentially life changing treatment. Austin, Texas.
Home to a young couple married for four years. Harry teaches English. Emily teaches ballet. They’re expecting their first baby. [EMILY] We had no prior indications that we’d be experiencing any sort of a complicated pregnancy whatsoever.
[NARRATOR] To learn that their baby had spina bifida was a shock. [EMILY] When we got those ultrasound results, It’s like everything took a 180. So we started planning a little bit differently. We read, we kind of educated, and we decided that fetal surgery was going to be our best bet. [NARRATOR] Emily has traveled to Sacramento to be the first patient in the CuRe trial.
[EMILY] As soon as we knew about it, we knew that it was probably the route we wanted to take.
[FARMER] She’s just turned out to be the perfect patient. I have so much respect all along for the women who have been willing to be the first. I mean, what an incredible gift they give to science. [NARRATOR] Now Emily and her developing baby have a surgery date at UC Davis at 26 weeks gestation.
The baby also has a name: Robbie. Robbie will receive stem cells grown at UC Davis. Another reason this campus is an ideal place for the CuRe trial: It’s home to a good manufacturing practice facility, also called GMP. GMP certification is given only to labs that meet the highest standards for safety and purity. At this stage of the trial, UC Davis had the only university GMP in Northern California that could manufacture these cells.
[PIVETTI] They have to be grown in a GMP facility if they’re going to be put inside a person. [NARRATOR] Scientist Priya Kumar leads the team that will be creating the stem cell patch. The patch will be applied to baby Robbie in a first-of-its-kind surgery.
[KUMAR] Excited. Elated.
Sometimes I’ve just got to pinch myself that I am in this team and I’m leading this work. [NARRATOR] It’s a process. The team suits up to practice over and over. [KUMAR] This is a time dependent process. Each day the time is very critical.
The time we pull out the cells, the time we seed on the scaffold, and the time we deliver the product. Everything should be like fresh and clean and no contamination. And it’s a bit stressful. [NARRATOR] There are failures during the dry runs, allowing the team to pinpoint and solve problems. [KUMAR] We did at least four test runs and that’s when we decided, okay, it’s a four day process.
[NARRATOR] The team also has to figure out how to safely transport the product from the lab to the hospital.
In the end, they draft a procedure manual. It’s 70 pages. They also decide to make backup patches in case something goes wrong. They’re leaving nothing to chance, especially Kumar.
[KUMAR] I decided, okay, let me sleep here. [NARRATOR] Who keeps a sleeping bag in her office ready to sleep there the night before the surgery. When it’s time, the stem cell patches will be driven in a specially designated stem cell mobile across campus from the lab to the hospital. One patch will be placed on the spinal cord of the fetus in the hopes of curing the damage from her spinal bifida and changing her life forever. [DRAMATIC MUSIC] It’s the morning of the fetal surgery.
Emily goes under anesthesia while the team monitors her fetus via ultrasound.
Pediatric and fetal surgeon Shin Hirosi oversees the team. They make the first cut. [HIROSI] We open mom’s abdomen, and we generally pull the uterus up and out of her belly. So we open the uterus and then we identify where the baby sitting.
And we don’t pull the baby all the way out. We just sort of float the baby up to that incision and we expose just the part that we need, which is the myelomeningoselse.
[NARRATOR] The myelomeningosele is the spinal bifida defect, an exposed sack containing the damaged spinal cord and nerves. Because the fetus is so tiny at 26 weeks gestation, the neurosurgeons use a microscope to perform their meticulous work on the spinal cord. With the surgery underway, it’s time for the stem cells to make their trip across campus.
Kumar and her team transport the patches that contain the stem cells to the hospital.
She slept in her office last night so she could keep a close watch over the cells. As the patches go on their journey, Kumar is thinking about her journey that brought her here. [KUMAR] Walking that corridor, carrying the bag was when my emotions started running through my mind about the whole process of being a scientist. [NARRATOR] The bags get handed off to the surgery team.
.. [FARMER] Nice job, ladies. [APPLAUSE] [NARRATOR] ..
.and the lab team can finally get some rest and will watch the procedure from another room in the hospital.
The patches are carefully brought to the operating room. [FARMER] Cells are arriving. [NARRATOR] One pack of patches is set aside as backup.
The other is opened. It contains two patches. Only one of them is needed, but both are prepared just in case. The surgeons have exposed the defect in the fetus’s tiny back. After years of research, the big moment for applying the stem cell patch has finally arrived.
[HIROSE] Cell side up. Right up. [NARRATOR] With great precision, Dr. Hirose brings the patch to its final destination. [HIROSE] Since the stem cells are on that patch, we need to place that directly on the exposed spinal cord, on the myelomeningocele and then so that to the dura or the covering of the spinal cord and then close the skin over that, creating a watertight closure and leaving those stem cells directly on the exposed spinal cord.
[NARRATOR] It’s the first time this has ever been done on a human fetus, a first in medical history. [HIROSE] I remember remarking just at the moment like, “Can you believe this is what we get to do? Can you believe that this is the kind of thing that we can do to help people? Can you believe that it’s taken so long to get here and we’ve been doing this for so many years? And finally, you know, we were able to put stem cells in a fetus.
” It’s just really an extraordinarily lucky feeling.
It really is. [NARRATOR] The surgical team stitches up Emily with great care and attention to detail. The procedure went exactly as planned. [HIROSE] It was wonderful that it was very boring.
Right? We want it to be boring. Excitement in the operating room, you know, is usually because something is going sideways. [FARMER] It was almost anticlimactic. It was perfect and perfectly smooth.
It was just fantastic. [NARRATOR] This first of its kind surgery is complete. [FARMER] Wow. So thanks, everybody. We’re done.
[APPLAUSE] [NARRATOR] Now the countdown to delivery begins. Emily undergoes regular ultrasounds, so the team can monitor the baby’s progress. [HEARTBEAT MONITOR] The team discovers a complication, one that’s unrelated to the stem cells, but known to happen with fetal surgery. [HIROSE] Her amniotic fluid levels remained low, and so we couldn’t send her home. [NARRATOR] Too little amniotic fluid, the fluid that cushions and protects the fetus and is essential for its growth and development.
Instead of living at the apartment she’s rented in downtown Sacramento, Emily’s new home for the foreseeable future is this hospital room.
[EMILY] It’s challenging, not impossible. So we’ve done what we can. My husband picked out this little quilt. So we have, like, our own bedding and that feels nice of course.
But I think it’s just bringing, like, your very simplest comforts and just like, items that may seem frivolous, but do make a pretty huge difference. [SEWING MACHINE] [NARRATOR] She passes the time by sewing costumes for her dance class back at home and visiting with family and the CuRe Trial team. [EMILY] They stop by multiple times a week. It feels like we’ve got kind of like a little home base kind of check in every week.
[HIROSE] A lot of those visits were really just to make sure that the fluid wasn’t getting worse or that she wasn’t have any bleeding or any problems with the fetus.
And we’re doing twice a day ultrasounds, looking at the baby, making sure that she was okay. [NARRATOR] Around 30 weeks gestation, Robbie provides some excitement. While fetuses with her degree of spina bifida typically have no leg movement, Robbie is kicking. [FARMER] The ultrasounds suggest that there is more leg movement in the fetus than they would have expected, given her level of lesion, which is pretty high. And Emily herself is describing what she says is lots of kicking.
Now, again, I try to manage her expectations too, but we are pretty excited.
[NARRATOR] Emily also is cautiously optimistic. [EMILY] I feel like it’s pretty easy to try and, like, rely on the facts and know that we’re doing very well overall. And that keeps me feeling pretty good, pretty optimistic. But of course, like, there are a ton of unknowns.
[NARRATOR] With each passing week, Emily and her family celebrate that Robbie is staying put and growing. They call it “happy not birthday,” a weekly celebration that Robbie has not arrived ahead of schedule. She makes it to the goal of 35 weeks. Robbie is ready to make her debut. By now, Emily has lived in the hospital for more than two months.
With just days to go, she’s feeling nervous, excited and just a little amazed to be making medical history. [EMILY] It’s larger than life. It’s enhancing quality of life for so many patients to come. It really blows my mind and it’s hard to understand just what it means and just how special it is that we got to be part of this. It’s delivery day for baby Robbie.
Harry is reunited with Emily for the birth of their first child.
[HARRY] It’s nice to be up here again since Friday and able to actually, like,be fully invested in this. [EMILY] Lots of kicking around. It’s like she knows that today is her birthday. [NARRATOR] Emily is scheduled for a cesarean section and she’s got some familiar faces from the trial team cheering her on.
[FARMER] Oh, look at that! [HIROSE] Hey, welcome back! [NARRATOR] What should be a typical C-section feels anything but routine. But the labor and delivery team is prepared, and the soon to be parents are ready to finally meet their little girl. [NURSE] We’ll see you in a little bit.
[NARRATOR] Emily is brought into the operating room.
She’ll be joined soon by Harry and Dr. Farmer, who leads the trial. Emily’s mother, Rhonda, spends the next 45 minutes outside the O.R.
doors waiting anxiously. [RHONDA] We hoped and prayed that her arrival wouldn’t come too soon. And now it’s finally time and it’s the most beautiful day ever [BABY CRYING] [NURSE] Ok, here we go. Say hello to the world! [NARRATOR] Baby Robbie, the first baby in the CuRe trial, the first baby in the world to receive stem cells for spinal bifida in utero, is here.
[BABY CRYING] She is the realization of decades of scientific work. The spot on her back where she had surgery appears completely healed with no abnormal growths, a proof point for the safety of the stem cell treatment. But what really captures the parents attention? This baby, who was expected to be born paralyzed if she hadn’t received treatment, is moving her legs, even wiggling her toes. [NURSE] Good girl!
[FARMER] Although we’re trying not to be too excited, there was early evidence that she actually had some leg movement. So, again, that’s way too early to tell.
But at the moment, things couldn’t be better and we’re really happy. [NARRATOR] Baby Robbie is brought up to the neonatal intensive care unit, or NICU. Across the campus, members of the trial team are nervously awaiting news from the hospital.
[PIVETTI] Knowing that something we worked on potentially had a life changing effect on this kid, it’s just, it’s really amazing. [WANG] Oh, my gosh. I was talking to Chris and I was texting him, like, several times, why is there no word? [NARRATOR] And then they receive a video clip of newborn Robbie. [WANG] That’s the moment that like, oh, my gosh.
Yes. The legs are so, like, choppy and so cute. Am I right? Yeah. [NARRATOR] Everyone is cautiously excited.
This is just the first case in the trial. There’s a long way to go before declaring success, but for today, they’ll enjoy the moment. [NARRATOR] The proof is in the pudding months from now.
But we’re, this is as good as we could have hoped for at the moment. We’re really excited.
[NARRATOR] At a rental apartment in downtown Sacramento, where the family from Texas has made its temporary home, Robbie turns two weeks old. Her family is captivated. [EMILY] Robbie is wonderful. She’s in very good health. She was born at five pounds, ten ounces.
She was about 19 inches long. [SNEEZE] Bless you. [SNEEZE] Bless you. It took a little bit before they could lift her high enough for me to see, but when they had her up, it was like, you recognize that baby.
Like, you’ve never seen her before, but you recognize her and you’re like, okay, yeah, that’s her.
It’s nice to see you for the first time. And then the second thought was like, how is she? Is she okay? [NARRATOR] Robbie is more than okay. She is vigorous.
Emily says she’s eating well, sleeping well and kicking. [EMILY] She shouldn’t be able to move anything below the hips. So to have hips and knees and ankles and toes and to have good strength in all of them too is pretty, pretty wild, pretty unreal.
[NARRATOR] Emily and her mother are preparing to head home with the new addition. They’ll return to UC Davis for Robbie’s checkups.
The trial team will keep a close eye on her growth, especially Dr. Farmer, who has a special role in the baby’s life. [EMILY] She’s kind of like her fairy stem cell godmother. [NARRATOR] For Emily, it’s been a difficult journey to get here. From the fetal surgery to living in the hospital for months to the eventual birth.
She did it for her daughter. [EMILY] It was never about me. From day one when we joined the trial, I was here and it was all about her. And that was a decision that was easy to make. [NARRATOR] Baby Robbie, the first patient in the groundbreaking CuRe Trial.
Her case is just the beginning. [FARMER] This could change lives forever. I don’t think I ever imagined when I started medical school that I might be able to have this big an impact on people’s lives.
[HIROSE] This job is is really a privilege. We get to be part of, you know, some of the most amazing moments for families and the downside is sometimes we have the biggest tragedies you can imagine.
But really, when things work, it’s just amazing. Our team at UC Davis is really exemplary, and I feel very lucky to be in a place where we have that many talented people that can make it happen like that. [NARRATOR] And UC Davis researchers are now exploring what else stem cells can do. [FARMER] Since we’ve seen such amazing results with congenital spinal cord injury, we are now looking at acquired spinal cord injury, other neurologic diseases that may involve inflammation. The ability to impact more than just one patient at a time is incredibly meaningful.
It is what is uniquely different about practicing medicine in an academic institution where part of the goal is the generation of new knowledge. Because that’s how medicine advances. [NARRATOR] Advancing medicine and improving lives. Robbie was the first baby in the trial.
Since then, a few more babies have become patients in this first phase.
The CuRe Trial team will continue to monitor all of them until they’re six years old with a key checkup happening at 30 months of age to see if they’re walking and potty training. For now, Robbie is crawling, kicking and delighting her parents. This tiny patient who made medical history, possibly helping to cure spina bifida in a trailblazing trial. [UPBEAT MUSIC].