(light music)
- Hi, I'm Susan Taylor with Scripps Health
in San Diego, California.
Stem cells, there's a lot of hype around them.
Do they work?
Are they safe?
And what about the role of 3D printing?
Can you imagine your surgeon
using a 3D printer right there in the operating room
to print cartilage, living tissue,
to then put into your arthritic knee,
to replace the bad tissue, to get rid of pain,
and to actually restore the function of your knee?
Here to talk about all kinds of advances
in orthopedic research is Dr. Darryl D'Lima
who is the Medical Director of what we call SCORE
here at Scripps,
the Shiley Center for Orthopaedic Research and Education.
Thanks so much for being with us, Dr. D'Lima.
- Thank you for inviting me.
- Sure, let's talk about SCORE.
When did it come into existence and what kind of wild things
are you folks doing there?
- So, SCORE was founded by Dr. Colwell, I believe in--
- Cliff Colwell.
- Cliff, right, Dr. Clifford Colwell,
I believe in the 1980s,
and it's been predominantly funded,
the major donor that founded SCORE
was the Darlene Shiley--
- [Susan] Who is a major philanthropist around San Diego.
- Right, right.
And originally, it was Dr. Colwell was doing work
on joint arthoplasty and you can imagine in the 1980s
not all joint arthoplasties were successful.
- Now, what's joint arthoplasty?
- Joint replacement. - Okay.
- So, replacing your arthritic joint with metal and plastic.
So, at that time, the technology was still evolving.
It wasn't as successful as it is now
and so, we were constantly chasing the new designs
not knowing in advance which was gonna be successful
and which one wasn't.
And Dr. Colwell did not want to rely on the manufacturers
advertising or marketing, so he started
by investigating his own patients.
That means he would have a database
in which every patient that got a joint replacement
would be followed up, for I think the longest followup
he had was 27 years to date.
So, he knew very quickly when an implant did not work.
And he was very meticulous in how he did the surgery.
He did them all exactly the same way,
so there was no other factor except for the change
in the implant design.
And I know of at least two cases
in which I was also involved where we found out
before the FDA and we found out before the manufacturer
made it public that the implant design was faulty.
And we then put it in thousands of patients
as the rest of the country did.
And so, that's how Scripps managed to help
their own patients because he was studying all these
implant designs very carefully.
- Talk about the e-Knee.
I know that SCORE was the only place in the entire US
that started testing what's called the environment-Knee.
- Right. - The electronic knee.
- So, the electronic knee also was the idea
came from Dr. Colwell because at that time
we didn't know what the forces were
inside someone's knee joint,
especially after joint arthoplasty.
- Joint replacement. - Joint replacement.
So, we were using computer models and engineering physics
to predict or calculate what the forces would be.
So, at Scripps we designed and we developed and implanted
an electronic knee, so it's functions exactly
like any other knee replacement implant.
But it has sensors, it has a computer chip,
it has a radio, it has remote power
and so it's sending data from the knee joint of the patient
outside to a computer that can track all the activities
that the patients were doing all the way
from walking, stair climbing, to sporting activities
and even skiing.
- So data from the e-Knee,
well, typical knees last,
joint replacements last what?
20 years?
25 years?
- Historically and statistically,
they last about 20 years with 80% success.
- So, data that you got from e-Knee showed
that your knee will last longer if you do what?
- So, at least from the standpoint of forces,
it seems like walking or running on a treadmill
generates less forces on your knee
than jogging outside, especially on uneven terrain.
- And biking? - Biking is safe.
We knew that tennis was not safe
because it's a high impact sport.
Surprisingly skiing, depending on the type of slopes
that you're skiing, for example,
greens and blues are okay, but when you get to--
- Stay away from the moguls. - Stay away from the moguls.
- And the double black diamonds.
(laughs)
And what about golf?
- So, that was a real surprise
because we didn't expect this,
but when you swing a golf club on your leading knee,
that means on the right-handed person,
his left knee would be the leading knee,
you can generate more than four times your body weight.
That means as you swing your club,
you're putting four times your body weight
which can be close to over 1,000 pounds on one knee.
- So, golf puts more stress on the knee.
- Golf puts more stress on the knee,
but unless you're a professional golfer
who hits the ball thousands of times,
the average golfer probably wouldn't have as much
of a problem.
- So, if you're lucky enough
to have a total knee replacement,
you probably want the knee to last longer,
you might have to cut back on your golf game
one or twice a week. - Right, that's right.
(laughs)
- So, let's talk about ostearthritis.
What it is?
- So, ostearthritis is caused by wear and tear of your joint
so there's this cartilage and it's articular cartilage
that lines the joint.
And that is exquisitely lubricated.
So, in normal people, the wear and tear is really low.
For some reason in some patients
because of trauma and some patients
because their bony anatomy is changed
or their knees are not lined correctly,
the surfaces start wearing out.
That now creates a reaction in the joint,
an inflammation in the joint.
And an inflammation begins to eat away
at the rest of the cartilage.
And so now you end up having a joint
that is swollen, that is painful
and as the cartilage wears away,
you expose the bone below the cartilage.
And so, when you have now bone loading on bone
you can get extreme pain.
- Can you repair a knee cartilage?
- At the moment, there's no clinically successful strategy
for repairing knee cartilage.
- So, what about introducing stem cells?
- So, the hope of stem cells is that in the body
the stem cells are the cells that actually produce
the tissues in your body.
And so, the scientific premise is
that if you take stem cells and put them in your body,
or put them in an arthritic joint,
they might now regenerate the lost tissue.
The tissue that you lost because of ostearthritis.
So that's the hope.
Unfortunately, that's not entirely true
because we are still trying to assess the efficacy
of why is it that some patients benefit from this treatment
and some patients don't and there's a whole line
of stem cell therapy that's in the preclinical stage
that hasn't even made it to patients yet.
- So, where are you in terms of the research now
being able to use stem cells to regrow cartilage?
- So, we are tackling this at multiple fronts.
For example, at the patients side of things,
what the FDA allows is to take stem cells
from your bone marrow and purify them
and then re-inject them back in our knee joint
or a disease tissue.
So, we are testing that in patients
trying to identify which patients actually respond favorably
to this treatment and which patients don't.
So, it's easy to imagine there are at least two factors.
So, there's the donor, that means my stem cells
might be better or worse than somebody else's stem cells.
And me as a patient, my tissues might heal or respond
differently to injected stem cells than somebody else.
So, our hope is that if we can identify the differences
between the patients that actually respond well
to the patients that don't respond well,
at a minimal, we should be able to preselect the patients
for whom this treatment is most indicated.
- Are stem cells less effective the older a person is?
What would be the ideal age
if I was gonna use my own stem cells?
- Right.
So, the answer is statistically, yes.
With aging, the cells don't proliferate,
that means they don't divide as readily
as stem cells from a young person.
With aging, they might produce less of the proteins
that are needed to regenerate tissue.
And then, with aging, you might also carry on
the diseases that that patient has accumulated
over the years, they might be reflected
in the stem cell population of that patient also.
- So then flip to the other end of the spectrum,
what about embryonic stem cells?
- Right.
So, that we are still in the laboratory
in preclinical stages of research.
So, embryonic stem cells now, as you correctly mentioned,
is the extreme other side of the spectrum.
These are cells that weren't even in a human body
or were only in an embryo, were extracted from an embryo
so they have no disease attached to them at all.
And they have this virtually unlimited capacity
for dividing, so from a few cells,
you can create thousands of doses,
so called doses of this cell.
The other advantage of embryonic stem cell treatment
is that you know what the potency of the cells is.
You know how well this cells can change
into a different cell type or can produce those proteins
or factors that we're interested in.
The downside of embryonic stem cells is twofold.
One is that, obviously, it came from a different human,
it came from an embryo, so there's a risk
of what's called the immune rejection
which happens with, say, organ transplants,
when they do organ transplants.
And the second downside is because the embryonic stem cell
can produce any tissue, and that's its natural function,
once we put it in the body, there's no guarantee
at the moment that it will only produce the tissue
we want it to produce.
What if it produces some other tissue?
And those are called teratomas.
- So, where are you,
I mean, if someone wants to sign up and they say
listen, you know, I want stem cells in my knee
'cause I've got terrible arthritis
and I don't wanna total knee replacement
and the great part about this is to think
that well, if we really could inject these stem cells
into the knee, then you wouldn't need
the total knee replacement.
It's faster healing, it's less expensive,
the person gets back to moving at the speed of their life.
If somebody wants to sign up,
I mean, how close are you to actually doing clinical trials
in people with this?
- So, with the autologous bone marrow derived stem cell,
that means stem cells from your own bone marrow,
we are already treating patients
with that type of stem cell treatment
because that's allowed by the FDA.
We are doing it under a clinic study
becuase we want to understand why it works
in only some patients some of the time.
We are also looking at other adult stem cells,
for example, there are stem cells in your fat
that have some promise.
That's not yet approved or allowed by the FDA,
and that we haven't started that study yet,
but we are getting IRB approval,
or approval from our human subjects research committee
to begin a study.
- [Susan] To see that it's safe enough to do.
- To see that it's safe and, right,
and that it actually benefits patients.
- Are you looking two years down the line
before you do the clinic trial?
Five years?
10 years?
- Yeah, it could be as soon as this year.
- [Susan] Oh really?
- Because the technology exists,
it's just the matter of making sure that we're doing it,
you know, we are following the regulations.
- So, technology,
we want you to just think about this for a second.
Technology is changing so fast when you look down the road,
when you peer into your crystal ball.
You know, what do you see five, 10 years down the line.
And we'll talk about that in just a couple of minutes,
but I wanna go back now and talk a little bit
about this 3D bioprinting which sounds like, you know,
science fiction, but you're talking about actually
taking a printer into the operating room
and printing live tissue out.
How does this whole thing work?
- Right.
So, most people have heard of 3D printing
and 3D printing is a different way of manufacturing objects
by from the ground up.
So, the traditional method of manufacturing an object
is taking a block of marble,
like Michelangelo did with David
and you take away the stuff that doesn't look like David.
The other way of approaching it is by printing David
drop by drop, you know, and building an entire structure
from scratch.
What we are doing is that we are doing it with cells.
So, we can now construct a three-dimensional model
of your tissue inside the laboratory.
And not only can we construct the shape
that matches the shape that's needed for the patient,
but we can also pick the cell type
and we can put the different materials in different layers
because we're constructing this droplet by droplet
and layer by layer.
We call it an ink because we are printing
and we call it bioink because we put cells in the ink.
So, after printing, you actually have now
a live tissue that has been artificially printed.
- It's so wild to think.
And most printers, though, today are like boxes.
You hope to have a printer with kind of a robotic arm
to actually print inside somebody's body.
- Yes.
So, it's a very ambitious project
and this was funded by the Schaeffer Family Foundation
that have been very generous.
And we've made progress with the box-like printers
to show proof of concept.
And now what we have is we've newly acquired a robotic arm
that acts like a surgeon's arm
and we put a print head at the end of the robotic arm
and now that robotic arm is technically capable of printing
inside a joint.
We haven't done that in live joints yet
and it's still maybe five, 10 years away from being tested
in patients.
- [Susan] So, if somebody wants to sign up for that,
it's a little premature for that right now.
- [Darryl] It's premature but, you know,
people sing up the infants for school.
- But you think about what's the benefit
to someone to have this 3D bioprinting.
I mean, you're gonna print like as a meniscus, right?
Explain that in terms of a meniscus.
- So, when you lose tissue from the body,
for example, you mentioned total joint replacement.
Now, even though the patient loses only a part of the knee,
if you have to do a total joint replacement,
you've got to remove the entire knee
and we have to now fit that plastic or metal implant
to the patient's bone.
So we're taking off a lot of tissue
some of which or most of it may even be normal
just because we've got to make the artificial implant fit.
Now, we don't have to do that.
We can only go in there and replace only
that part of the tissue rather than resurfing
new entire carpet, we only replace the part of the carpet
that is worn or stained
or the one that requires replacement.
- So, it's faster healing.
- It's faster healing--
- Less trauma to the body.
- Less expensive
- And less expensive. - to the patient.
- Maybe you should be writing implants.
(laughing)
- No, no, no.
Are there risks to this?
I mean, what are the risks?
- There are obvious risks, for example,
we've got to show that the robotic arm is safe,
but robotic arms are being used
in a lot of technology today,
for example, manufacturing especially cars.
So, that's a technical risk.
There's a risk that the ink could cause a reaction
to the patient and there are ways to test for them.
And then there's a risk that the cells
might create something that's unanticipated,
especially of the stem cells.
- So, how is SCORE tackling the challenges facing
this tissue engineering?
- So, we are moving stage wise.
So, we have a pipeline what we call a translational pipeline
when we take technology that's discovered in the lab
to the patients.
And so, we're lucky that under one roof, one umbrella,
one Scripps, we have capabilities to do laboratory studies,
where we do cell culture and tissue culture.
Then new have preclinical studies
where we have animal testing and big machines
that do mechanical testing of clinical sized product
and then finally we have
a very large clinical research services department
that runs dozens of clinical trials.
- [Susan] So, it's one stop shopping.
- It's, for us, at least it's a one stop shop.
- All right, so we talked about this a couple of minutes ago
so now, let's talk about the future discoveries
or therapies that SCORE is working on.
If you can, you know, peer into your crystal ball,
what are you most excited about looking five,
10 years down the line?
- So, I still think that some of the work
that we are doing now might take more than 10 years.
But if I had the time and the resources,
one of the excitement about stem cells,
they're like drug factories.
So, stem cells produce a lot of proteins and other compounds
that can heal diseases, can even slow down aging.
So, what we are doing now is we don't know
what the stem cells do, so we are putting in the factory
inside the patient.
But if we could tease out all the individual proteins
that the stem cells are producing,
maybe we wouldn't have to go back to a stem cell to do it,
we would just have to give that specific protein
or that specific disease-curing drug to the patient.
So, that's one of the...
One of the area that I'd like to explore.
- Well, we are so appreciative of all of the research
that you're doing and how you translate that
to actually helping patients live more longer,
more productive lives, so thank you
Dr. D'Lima very much. - Thank you.
- If you would like to learn more information
about the great research that Dr. D'Lima and his team
were doing at SCORE,
the Shiley Center for Orthopaedic Research and Education
at Scripps, please just click on the link.
If you'd like more critical information about your health,
we take care of you at Scripps from head to toe
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and also follow us on social media @ScrippsHealth.
I'm Susan Taylor.
Thanks so much for joining us.
It is our mission at Scripps to help you heal, enhance
even save your life. (light music)