A Woman’s Journey Palm Beach 2018 Panel Discussion on Regenerative Medicine

A Woman’s Journey Palm Beach 2018 Panel Discussion on Regenerative Medicine


>>I get the opportunity
to say very briefly what regenerative medicine is, Deb. We have an amazing panel
here, so I’m gonna keep my introductory marks to the topic very brief so we can focus on the exciting work of my friends and
colleagues that we have here on the panel. You heard very quickly
but just to reiterate, we have Dr. Louis Garza from Dermatology, Dr. Jennifer Elisseeff from
Biomedical Engineering, Dr. Justin Sacks from Plastic Surgery and Dr. Patrick Byrne from Otolaryngology. So what you’ll appreciate
is that we have a multi-specialty panel. And regenerative medicine,
which seeks to replace tissue or organs that have been damaged by disease or trauma or congenital illness or growths of that kind, it seeks to replace those tissues. And the way it can do
so is three main ways. So the first is with tissue engineering and the second is with cell therapy and the third is with artificial organs or medical devices. And it’s a relatively new
but incredibly exciting field and you can imagine that it
requires a multi-disciplinary multi-specialty team to come
up with these incredibly innovative ideas in healthcare. Thus we have brought you
today an equally innovative and dynamic multi-disciplinary team and so they’re gonna share
with us some highlights of their work. And I think you’ll be truly amazed at what they’re doing with their
research up in Baltimore. And with no further ado, I
promised that my main job was to be the keeper of the time. So, Dr. Garza, please kick us off.>>Sure, thanks Dr. Ishii. So regenerative medicine
has a lot of promise in the way we think
the ultimate promise is to ask what if you could
grow a new liver or lung if your your first one failed. And the reason why that
should be possible is that every cell in your
body has the same DNA. And that DNA is kind of
like almost computer code you can imagine with a
bunch of applications in it. And those applications are really amazing. And when you were in your mother’s womb, one of those applications
was grow a heart, grow a liver, grow a lung. So every cell in your body
has these instructions, and the question is why
can’t you reactivate them as an adult. And there’s examples of
this already in nature. So if you look at the salamander,
we say that this model kind of is our lodestone
that points north for us. If you cut off its arm, it
will grow an entirely new arm even faster than it grew the first one. And so there’s already examples in nature where she’s shown us that this can work. So my lab is really excited
by that and interested in that and that’s what motivates us every day. And we try to use the
skin as a model system. Because in science when you
tackle these large questions, you have to kind of take
a reductionist approach and look at smaller ones. So we look at the skin
and we say can we induce organogenesis again in the skin. And we look at it in one
context in large wounds where when I was a medical
student and a resident I was told, well if you have
a wound that’s very deep, you can’t grow a new hair follicle ’cause it’s too complicated. It has too many stem cell compartments. There’s too many different cell types. It just doesn’t happen. But in the laboratory
that I did my post doc in, they noticed that if
you do enormous wounds in the back of a mouse at the very center, they act like they’re embryos again. They act like they’re
in their mother’s womb and they make a new hair
follicle out of nothing. And so we look at that
model to try to understand if we can promote
organogenesis again in adults. The second half of the lab
it say, okay if we can’t grow a new limb now, can
we at least help people who have already lost a limb. So people who have had amputations that are using prosthetics. So there’s been major
investments in prosthetics including at Hopkins like
with a Luke Skywalker arm that they made in the applied physics lab, which was an automated arm
that’s directly connected with neural inputs. When I visited Walter Reed for example, I saw that all the prosthetics
that weren’t being used were plugged into the wall. So there’s major
improvements in prosthetics but there hasn’t been
as much attention paid to the skin interface. And so what my lab is trying to do is, if we can’t grow a new
limb, can we at least regrow the same thick type of skin we have on our palms and soles at
the site of the amputee at the stump. And because you didn’t
think twice when you put your shoes on this morning, and that’s because your body has been evolved to bear weight and bear pressure
at your palms and soles. So why can’t we try to
re-form that same thick type of skin at the stump site of an amputee. And like all of our projects, we start from the molecule where we do stuff like mass spectrometry. We do cell culture where
we’re looking at cells. We look at my different mutant mice to see what they can teach us. And then we also try
to take it all the way to the clinics. So we’re even doing stem
cell trials currently on that last project for
example where we’re trying to change skin identity
on first normal subjects and then eventually on
amputees so we can ask how we can improve their lives. And so that’s the example
of what we’re doing in regenerative medicine.>>Wonderful. (applause) Right on time. Dr. Elisseeff, please.>>So I come from an
engineering background. And I think one of the great things about being at Hopkins is
that engineers can work together with clinicians to
provide new clinical solutions. Engineering can also
be considered a bridge between the basic science,
these new discoveries and how are we gonna actually
have this help a patient. Right, there’s a lot that
goes in to taking this basic science discovery and
build a product out of it that can be delivered. So I can go my surgical
colleagues and say, well, what is the problem
that you face the most today. What are your biggest challenges? And we go back to our sort
of engineering design, come up with a prototype,
and then can go back to our surgical colleagues and say, what do you think of this? And like well, this is
great but I don’t like that. So we go back and redesign. So that applies to the field
of tissue engineering too. So tissue engineers, are sort
of the evolution of devices. So you think of artificial
hearts, artificial knees and hips, those replacements
were able to perform the function of the knee and the hip. But they’re not yours. They’re not made of the
same thing in your body. So what tissue engineering
is trying to do is give you a tissue replacement that is
actually from your own body. So initially the field
developed such that we built biomaterials that served as a
temporary scaffold for cells. And that temporary scaffold
would give directions to those cells to grow
and make new tissue. Then the scaffold goes away
and what your left with is just your functional tissue. So we noticed when I
first started at Hopkins a few decades ago that
this was very exciting but it wasn’t reaching the clinic yet. So we went and looked
at building materials that we could use to induce your body to repair itself. So we have some repair
capacity, maybe not as good as the salamander, but
there’s still some there. And how can we put in
materials that will direct your body to be able to repair better. We first started in
cartilage in the knee joint, and now we’re moving to soft tissue. We’ve done a couple of clinical trials and the ability to not
just design products with our clinical
colleagues, but to actually translate those and run clinical trials had a huge impact in helping these things to reach the clinic, but also teaching us what we should be looking
at in the laboratory. And one example of that goes back to what we heard about this morning, the immune system. So in one of our clinical
trials we noticed that the immune system seemed to play a really important role in
the biomaterial response. And so I didn’t really know
anything about the immune system so that was a great opportunity to go away on sabbatical
and learn something about it and come back to Hopkins and work with immunology
colleagues at Hopkins to see how we could
leverage your immune system to promote tissue regeneration. We’re calling this
regenerative immunology. So we’re very excited about that. As a future, you know
we’re really not working with stem cells too much
anymore but how can we use immune cells to help
direct your body’s own stem cells and other
capabilities to regrow tissues. Now we had some collaborators come to us and talk about the challenges
of both regeneration and chronic disease associated with aging. And so why is it harder to repair things, repair your tissues when you’re older? Well there’s a cell type
that accumulates with age called a senescent cell. And initially we thought
well, this senescent cell is just tired, it’s pooped out. It’s not dividing anymore. But it’s not actually
just a quiet bystander. It’s secreting a lot
of things that promote inflammation, the negative
kind of inflammation that is affiliated with chronic disease and also impedes regeneration. So we’re looking at
ways that we can get rid of these cells so we don’t
have any more of these sort of senescent
bystanders that are impeding the local environment, and we can put in our materials. We can put in our technologies to induce your own repair capacity
or work with stem cells to try to rebuild new tissues. So it has been slow over
the past decade or two, these technologies reaching the clinic. But I really believe there’s
a real revolution happening now with new approaches and
real practical technologies that come from working with
our clinical colleagues understanding what is feasible to work in the doctor’s office
or at the surgical suite. What do we need to do to design something that will solve those problems in addition to the biology of rebuilding your tissues.>>Dr. Ishii: Amazing, and
that’s a perfect segue, Justin, to you and what you’ve been working on in your research.>>Thanks so much for
having me here with this incredible panel. So it’s lunchtime in
Florida, so I’ll tell you a little bit of a story about myself. So I’ve lived in two different countries and four different states
in the past 20 years. I’ve trained all over the place. And I’m a surgeon-scientist. And I came to Baltimore seven years ago because I wanted to be at the interface of an incredible academic medical center and the ability to help treat patients and do innovative things. So I do cancer, trauma,
cosmetic reconstruction head to toe. So I’m a plastic surgeon. And my mother always
wonders why I just didn’t open up the office on
Fifth Avenue in New York and practice, but I keep telling her that I’m trying to do things, I told her that could still happen, but until that time comes, I’m
gonna do some great things. I’m gonna work with some great people, like the people around me. And so we work in this very
collaborative environment. So when I got to Hopkins seven years ago, I’d come off a faculty
position at M.D. Anderson where I was treating cancer. I do cancer reconstruction all the time down in Houston, Texas. And all I do is cut people
to help make them better. So I do a lot of head
and neck reconstruction and breast cancer reconstruction,
extremity reconstruction. I do a lot of breast
cancer reconstruction. I do a lot of it even more so now because of genetic testing where women know ahead of time now, they know
their genetic destiny. So they’re coming to us at younger ages asking for mastectomies, asking
for breast reconstruction, asking to feel normal, to feel feminine. And so the challenge
that we have is how do we do this well. How do we do it without
hurting the patient. And every day I cut
somebody, it’s not easy ’cause you have to make somebody worse to make them better. So seven years ago I’m at Hopkins. I’m doing breast
reconstruction and I’m working in this amazing environment
with great scientists and collaborators, and one of my residents who had just started his
M.D. PhD, Shushawn Coretti from Harvard, and the two of
us were just in the office, how are we gonna do this
to make this better. How can we find ways so we don’t have to cut people anymore. And so we started talking
about tissue engineering and ways that we could
maybe make something, synthetically create
something that we could either place into a patient or inject into a patient. Off the shelf kind of stuff. So I would be busy in the operating room and Shushawn was looking
around, and I said search for the best biomedical
engineer that you can find that works with scaffolds. So we had Dr. Elisseeff on the floor, we had Dr. Hosh Wanmal. We bumped into Dr. Hosh
Wanmal, and Sushawn comes back to me and said I found this person. I said great, when are
we getting on the plane to travel. He said he’s across the
street in the Smith Building. I said great, let’s go meet him. So we went across the street,
it’s next to my clinic, next to the operating room,
and we said here’s the clinical problem. We want to reconstruct a
woman after a lumpectomy or a breast without using their own tissue or without placing an implant. You know at first, I can’t help you. It’s too difficult, all
these different things. And then eventually he said,
well I have this scaffold we’re tinkering with. We can make it out of
FDA-approved synthetic fibers, hyaluronic acid, women
and men get it injected in their face and it’s for
fillers, and he can mix it with polycaprolactone,
which is suture material, link it together. It’s like jelly with
fibers going through it. So we now have four patents pending. They’re being reviewed right now. We started a biotech
company at Johns Hopkins. Johns Hopkins has skin in the game. We have skin the game. It’s an innovative environment. We’re doing animal research now. We’re moving to fast forward
which is down the block. They’ve built a hotel,
they’ve built houses for companies. It’s at the interface
of industry and clinics and academia. And what we’re doing is
we’re looking so that when I do a breast
reconstruction in the future instead of taking tissue from the belly and transplanting it, which is what I do for eight, 10 hours. I have to do this tomorrow when I go back. I’m reconstructing a woman’s breast using her belly tissue tomorrow. I’m transplanting it. She gets a tummy tuck
and she gets a breast. But it’s still, I have to cut her belly. And for everybody that’s
not an easy thing. If it was my belly or an
older person maybe whose had a couple kids, that’s not a big deal. But for a younger woman
whose never had children and works at all time,
that’s not a great option. And breast implants, they’re
not the best option anymore. You hear about anaplastic
large cell lymphoma. There’s a T-cell lymphoma
that’s identified with breast implants now,
certain breast implants. There are things that
we have to worry about. So my job, and why I love
running to work every day is I get to run to work and meet patients and help them. I get to run to the laboratory and work with people who are thinking about ways to make better scaffolds
that we can inject into patients and let the
body do what it does best, which his heal itself. So our scaffold, the hopes is to be able to mix it with the patient’s own fat, allow the fat to integrate
and to grow more volume. We’re gonna start in the face. We’re gonna hopefully go to the breast. But this is why my job is so exciting. This is why I can tell my
parents, I’m okay in Baltimore. I’m okay at Johns Hopkins. I’m doing something that
you might not understand. It might not make sense
to you, but it’s gonna make sense to many, many, many people besides just one or
two patients at a time. And so it’s a really beautiful place, the academic environment, the hospital. There’s so many ways
that I’ve seen patients help with the clinical interventions. And really the scientists that we support and the surgeon-scientists we support, with the federal funding,
the research dollars, their philanthropy, it
really goes to good use. You know, we are really
using funds that we obtain in grants and given by other donors to do good science and to do good work. So, that’s my story and
thanks for listening. (applause)>>And what Justin just said,
I bet you can ask any of us, why on earth do you live in Baltimore, especially when we’re
down here in Palm Beach. And we would say, ’cause
that’s where Johns Hopkins is. That’s why we’re there. Thank you, Justin. Dr. Byrne, round us out.>>Yeah so my specialty
is facial plastic surgery, and I’ve been at Hopkins for 16 years now. And my interest is in
how regenerative medicine can be sort of merged
with surgery to improve our outcomes. And it’s driven by the patients we see. So I’ll tell you about two patients. We have one patient now
who is a wonderful guy who about 15 years ago
suffered a shotgun injury directly through his face. So he has no normal
structures in his face. He has undergone dozens of surgeries. He can’t open his mouth. And the only solution we have for him is through our face transplant team. So one of my roles is
helping lead that team. Dr. Sacks and I have
spent countless Saturdays for the past two years custom designing a surgical technique to repair and replace this wonderful man’s entire
face, nose, upper jaw, lower jaw, lips, eyelids,
everything, right. In an ideal world, you know
you hear about these stories, you’ve probably seen the
picture, I’m sure some of you have seen the picture of the mouse with the ear on its back. Have any of you seen that picture? Do you know what year
that picture showed up in the press? It was 1999. There’s still no tissue engineered ears in use clinically. But in an ideal world, a patient like him could be served by whipping
up or 3-D printing a face. But in reality, a lot
of times we have I think opportunities for meaningful improvements by merging surgery. He needs cartilage, he needs soft tissue. He needs so much it gets pretty complex. We have another patient though who, he’s undergone 42
operations for a congenital vascular malformation of his nose. Which means most of his
face is fairly normal but his nose is completely dysfunctional and doesn’t work at all. He’s interested in a nose transplant and we’re working on that. Now the question arises,
both of them are alive right, and functioning, working,
have good meaningful relationships but they’re
willing to undergo an unbelievably complex operation with lifelong risk of immunosuppression. And the question is, why? Well there was a survey
done a number of years ago and they tried to assess how
much risk are you willing to undergo for a transplant. ‘Cause you’re gonna be
on medicines for the rest of your life and that puts you at risk for greater problems in the future. If you compare liver transplant, people who have liver failure,
kidney transplant patients who are dependent on dialysis, or people with facial deformities, the
last group is more willing to die because of the treatment than any of the other groups. So people with terrible,
terrible facial deformities are very, very problematic. And they really suffer in life. So if you’re a surgeon
taking care of these folks you look across the hall
just like Justin described and you look for solutions. So a couple of the
solutions, there’s dozens in a place like Hopkins, but a couple that we’re working on,
one is, you can think of your nose as this three-dimensional, semi-rigid structure over
which the fabric is draped. And the structure is mostly cartilage. But the problem is cartilage
isn’t a great material to build beautiful things
with or functional things. If you take a chicken wing,
I would challenge you, take a chicken wing and
try to carve and bend it into something beautiful. And then, it has to be so good that you’re comfortable having it in
the middle of your face for the rest of your life. It’s just not a great
artistic material, cartilage. So we’ve learned that you
can, instead of carving individual pieces of
cartilage, you can chop it up into a million little
pieces and then use glues. So Dr. Elisseeff has
invented a type of glue specific for cartilage to
help them knit them together. And the promise it holds
is that it can take these little millions of little
pieces and create a perfectly formed structure that will
actually last in the body. Another invention that we’re working on, and we just finished
a phase one FDA trial, is taking human fat out of
donors, so from cadavers, processing it in a way
that cells are eliminated, and it can be reintroduced
into the human body to replace soft tissue. It clearly can replace
fat but it may be able to replace and stimulate the generation of other types of tissue
like muscle as well. So what some of us foresee as being able to take elements out of labs from geniuses like Dr. Garza and Dr.
Elisseeff and then help surgeons like us improve our outcomes. And that’s really drives a lot of us. (applause)>>Patrick, you mentioned
the human testing that you’ve gone through. Can you tell us about that process?>>Yeah from an idea,
something that starts with an idea, Justin and his buddies said, God, we got to find a
solution, the pathway to go from idea to clinical
use can be complicated. And a lot of it depends on what
type of a technology it is. In the case of the
material I just mentioned that Dr. Elisseeff actually invented, it’s considered what’s
called a biologic by the FDA. So it means that it’s more complicated than some other technologies to introduce in patient care. So in order to get it to
use in someone in this room or your mother or father, your children, it means we have to go
through animal testing and then it has to go
through human testing in a sequential ordered fashion. And in our example we did
what’s called a phase one trial. So the first step is, is it safe? And you use it after extensive review and a lot of approvals, you use it in a small number of patients. And we actually know that that’s the case in ours because it worked pretty well. The next is does it actually work? So our upcoming step would
be, we’re gonna find patients with soft tissue defects,
and we’re gonna inject this material and keep it fairly simple, and see if the material sticks around, if it regenerates normal fat. And then we would go
into a phase three trial and through that final phase three trial is where the hope is
that it can be actually introduced into clinical care. So it’s a sequential process.>>Thank you. So along those same lines
Justin, your scaffold, base case scenario, everything goes well, when can we anticipate that being a real reconstructive option for your patients?>>I think based upon, so
what Patrick and Jennifer have is a biologic. We have a synthetic scaffold. The products that are in
it are already FDA approved but it’s the combination
of how they come together. This still has to go
through regulatory review. But we will be within the next year, doing some clinical
trials where we actually inject the scaffold most
likely into the facial region to see how it fills. And then hopefully if we
have good safety testing, it will still go along
the lines of the same regulatory pathway. So best case scenario, probably
within one to two years of actually potentially
human use, which is still a very optimistic pathway
forward, but this is what we’re trying to do. We work with a facility
down here in Florida that’s making the
scaffold and developing it based on specifications which are created by the biomedical
engineers, and we’re testing in the laboratory, and the hope is to move it forward rather rapidly.>>Dr. Ishii: So we’ll have
you back down in three years with some actual patient results.>>Yes, I mean that’s
the best case scenario.>>Shifting gears a little
bit, Louis, so tell us about fractionated lasers and their role in regenerative medicine.>>Yeah, that’s a funny question. So I’ll tell you an interesting story of how again mother nature
has just really conserved ways that she approaches problems. And by looking at a lot
of different contexts, you can see the patterns
that she’s kind of showing us for her solutions. So we were looking at
regeneration in two very different contexts. So I already told you about one of them where we do these enormous
wounds in the back of a mouse and in the
very center they make these new hair follicles. And we can say, and there’s
different strains of mice, just like different types of
people say, oh I scar badly or some people will say I scar well. We have different strains of mice. And we had one strain that
didn’t regenerate well, and we had another strain
that did regenerate well. And we tested their genes on a gene chip. It’s like the size of my
fingernail, and it tests every single gene that exist, and we asked what were the genes that are associated with high regeneration? And we had been working
on that list for about, I don’t know, three or four years. And then somebody else, there was a great cosmetic dermatologist,
Mary Sheu who works closely with Dr. Byrne for example and in our department. And she was really curious about how laser can help people look younger. So a lot of folks have
for example, they use the fractional restore
laser, and people can get it on their faces and it can
kind of help with wrinkles. It can help sometimes with pigmentation. And so with some funding from a company, we were able to take biopsies
of some kind volunteers where we did before and
after laser, and we could say we know these patients had
rejuvenation of their skin, what were the genes that
changed in these patients. And the really fascinating
thing is, we found the exact same genes in both the mice and in the people. And it’s this pathway that’s called your innate immune system
for double-stranded RNA. So your body has all
these ways it recognizes infections, and it turns
out it’s your body’s co-opted some of those mechanisms to recognize infection to
instead kick off regeneration. And we’re seeing that
same process both in mice and in people. And it’s another good example I think of the collaborations we have at Hopkins and the way by working together we can try to find some of these really cool common underlying concepts in
regenerative medicine.>>Excellent, and that
Jennifer, you alluded to the immunoregeneration as well. Can you, the final question for you though is the senescent cells that you described and their role in aging and rejuvenation. So you talked about removing the cells. You talked about they were
expressing harmful products that led to aging. So two things. How do you envision that
ultimately playing some clinical role, and could you possibly rather than removing
the cells, could you do something to inhibit the products that were being secreted so that they couldn’t have the downstream effect?>>So we first started
this project looking at senescent cells with
arthritis of the knee. So if you damaged your knee,
if you have a meniscal injury or anterior cruciate ligament injury, it starts a process of degeneration. And we’re wondering why. We know there’s a lot
of inflammatory markers in these diseases, but
what was the source of it. So it was perceived that
senescent cells are there when you have an injury. So when you do cut your
skin, senescent cells are important for calling
in the immune system. But the problem comes when
they don’t get cleared away when the injury is repaired. So in the case of
cartilage, our body can’t get rid of those senescent cells. The immune system can’t
get into the cartilage and eat up those senescent cells like they would normally do in a
wound healing process. So we found that if we use
drugs to selectively kill those cells, we can really
target the foundation of the disease and inflammation. And while there are some
potential mechanisms to target what they’re secreting, you would have to keep
giving those over time. Whereas if you target the real source of those negative products,
you can do that once and be done with it.>>I think we heard from
this panel the promise of medicine. And I think what’s
incredibly exciting is that we have the potential to appreciate the clinical impact of your
research in the very near future. So thank you for your amazing work and thank you for sharing
it with all of us. (applause)

Leave a Reply

Your email address will not be published. Required fields are marked *