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I think medicine isn't such an interesting state right now.
A lot of people are railing against different elements of medicine and healthcare system
stuff like that and then we see this field of regenerative medicine sort of emerging almost
like out of the ether like in the mode of a savior.
And I feel like there's there's a lot of hope and there's a lot of hype and I want to
go into a bit of that with you and then I'd love to dive into some of the specific modalities
that are getting a lot of attention and really talk about them and what the future holds.
But when we use the phrase regenerative medicine these days just more broadly.
What are we actually talking about here?
Yeah, at a very basic level the best way to understand it is we're just trying to repair
or fix tissue back to the way it was.
So instead of cutting things out.
So for example, if you have a bad knee right now they may take it out and they'll put
in a new knee artificial one.
But imagine if we can grow you a new knee sort of speak or grow you some new cartilage.
So that's the idea or promise of regenerative medicine.
Obviously this concept has been around for decades but we're finally as Arnold Kaplan
put it who's a kind of pioneer scientist in regenerative medicine that we're at the
beginning of the end sort of speak.
So meaning the end of just like the scientific discovery area and now we're actually beginning
the actual clinical translation of everything that the last 30 years of science has taught
us.
So is it possible that things like knee replacements or like a lot of what's orthopedic
surgery today in 10, 20, 30, 40 years will kind of look back at that and say how unorthodox
we ever allow that to happen.
Oh, there's so many.
I think in 30 years I think we'll look back and we'll be like wow I can't believe this
is how medicine used to be.
From all chronic diseases not just orthopedic but all cardiovascular disease, COPD, psoriasis
inflammatory conditions, even cancer is going to look very archaic in 30 years from now
because right now it's just a nuclear approach which is just kill all your cells in the body
including the good ones with chemotherapy and eventually it's going to be designer cells
that I believe will be the solution to a lot of these.
As we've already seen and this is stuff that's already happening now and it's only getting
more sophisticated as time goes on.
So it's not something that's 50 years down the road.
It's already happening in practice and I'm obviously treating patients already with
a lot of these technologies and the results are only getting better every year because
the technology keeps getting better.
Yeah, I'm curious just on a personal level.
When you decide I'm going to enter the field of medicine, did you know from those early
days, oh this is the particular branch that I want to go into or did you enter it and
then something happened?
No, we're trying to medicine is not even a thing in medical school.
We were taught anything about, I mean we're taught embryology and obviously stem cell biology
but there's no like regener and medicine curriculum or anything like that.
And so it was more almost out of frustration of not being able to help people the way
I wanted to help them especially because I started out as a sports doctor and family
doctor and in primary care medicine and sports medicine.
It's traditional medicines quite not only mundane but a lot of patients don't get better
and the options are basically just cortisone injection if you have pain, physiotherapy, acupuncture,
shockwave, you know some stuff like that and if that doesn't work then they send you
off to surgery and a lot of times patients don't want surgery and sometimes surgery is
risky or dangerous or they can't even do surgery.
So then you have patients with chronic pain who are living with it and suffering and there's
no one to help them and that's really got me into it because chronic pain is not an
easy field in general but it's also one of those things that affects more than just
quality of life because as we probably all know now longevity is highly correlated with
movement and exercise and putting on muscle but if you're in chronic pain you can't really
exercise, you can't move properly, you can't load the muscles the way you want so your
health deteriorates and then chronic pain is also associated with mental health issues
depression, a lot of times chronic pain patients have history of trauma and so there's all
these other factors that interplay into it as well and that was my big driving force,
just helping these people that no one else seemed to want to help and then I just started
helping them at which period of medicine and it just went from there.
Yeah, I'm curious also because when you make this left turn, you're doing this thing,
you're using all the traditional modalities, you're following standard of care that has
been standard of care for generations at this point.
And you're doing the thing and you're like okay so sometimes it's working but oftentimes
it's not and then you advance to the next level and that thing sometimes it works.
I mean I think we've probably all heard countless stories that maybe folks listening in have
proceeded all the way through surgery and then gotten through that and gone through the
rehab and then they're still actually not better and I can't imagine the futility that
sets in when you figure like okay I've done all the things, I've checked all the boxes,
I paid all the money, I've endured all this suffering and the added pain and the recovery
and I'm still not feeling better. On an individual level that can be brutalizing and I imagine
for a physician that's also got to be like psychologically kind of brutalizing.
It is and that's actually why most physicians are burned out. It's not because job satisfaction
is highly correlated with your ability to help your patients because that's why we become
doctors. So we want to help people at a very fundamental level, most doctors and so if
you can't see your patients get better it becomes very frustrating and you start getting
burned out and a lot of doctors are burnt out because they're working in a broken system
and they're not able to provide meaningful solutions to their patients. It's just a revolving
door or it's just kind of a band-aid solutions and there are obviously traumas and stuff
like that where surgeries needed and you have to get surgery but there's by far the vast
majority of the reason our healthcare system is breaking down is exasperation of chronic
conditions and increase in chronic diseases and we know these things are majority preventable
with lifestyle. Over 80% has been the statistic that's already published so why don't people
change and then there's so many other issues on that. So I think we're kind of almost past
that point where I'm kind of like okay people are going to be people are it's also because
our environment is set up for failure. It's so hard to live a healthy lifestyle when
we have an obesogetic environment with toxins, foods, everything that that shouldn't be
approved and the food chain is approved and and so it's just all these other factors that
make living healthy lifestyle really challenging but Regina and medicine has the ability to increase
your physiology and your resiliency so you can deal with the modern environment and you
can live a healthy lifestyle easier and that's to me is the most impactful thing about what
we can do for a lot of people. Yeah I mean that sounds very cool so when you make this
decision and you're like all right this isn't the path for me I want to take this other
path and like you described you didn't get any training in this in med school I'm curious
how do you actually go about saying I need to actually understand what this is and get
trained and copied out on a level where like I feel like I can turn around and offer
this to patients. Yeah I guess this is like that quote where it's like everyone goes
left and then you go right and then you kind of left on your own trail and trying to figure
it out so that's that's what I did and I was fortunate because of doctor and Canada doctor
Anthony Gallia who is kind of a pioneer in platelet rich plasma injections which is older
technology now but something that was used quite a bit in regenerative medicine for muscle
tears and tendon tears so a lot of athletes were doing it and so I got fortunate to work
with him on that regard and I learned a lot but then I traveled traveling into Asia traveling
into Europe middle east and all these other places where hey guess what they've been using
regenerative medicine a long time and especially in Japan which is probably the birthplace
of cellular reprogramming and all this genetic modification to cells and kind of the holy
grail of regenerative medicine really which is making an old cell young again the Yamanocha
factors that was birthed in Japan and so that alone made me very curious about Japanese
culture and everything and so when I worked there I learned a ton and then just kind of
shadowing different doctors and learning and then putting it all together because instead
of looking at the body in a siloed approach which is still what most doctors do with chronic
disease there's more similarities than there are differences between chronic illness there's
something called 12 hallmarks of aging and if you look at them they tend to repeat themselves
with not just aging but with heart disease with neurodegenerative conditions with cancer
with osteoarthritis is all the same root cellular dysfunctional patterns that drive the illness
and so once you start seeing themes and patterns and repetition then you put the pieces together
and I guess I was I managed to put the pieces together I think before a lot of other people
did maybe then that's why I've been able to be very fortunate in helping some patients
that no one else has been able to help and then you get a reputation for helping these
patients that no one else can help and word spreads pretty quickly especially amongst the
communities that I'm working with you know slide reads and high networks people and stuff
like that.
Yeah I wanted to dive into some of the different modalities and get even a little bit
into the weeds with you because I think each one there are a lot of questions people have
probably heard about them like are they real are they not where they for the way not for
so you just brought up one that I think it's probably the one that a lot of people hear
about and talk about commonly short handed off in this PRP platelet rich plasma what are
we actually talking about what is that?
Yeah I like what you said at the beginning of the talk which was hope or hype and that's
really the biggest problem with regenerative medicine still is the lack of standardization
and the amount of unfortunately charlatans and predatory doctors who are claiming the
regenerative medicine experts and don't really know much and are just trying to make a
quick buck off a patient.
With that said and that's a big problem with PRP so platelet rich plasma is where we take
your blood we centrifuge it and when you spin it real fast it separates into different
layers and the plasma kind of sits on top and you can isolate that because when you centrifuge
it concentrates the platelets hence the name platelet rich because it's rich in platelets
and those platelets actually release growth factors and signals to reduce inflammation and
promote regeneration so they send signals to repair tissue but those signals are relatively
weak so they don't work for many conditions they work for really only muscle tears or
tendon tears and usually not chronic degenerative stuff but more acute is really rare shines and
even then the problem is again is lack of standardization there's different types of PRP if you
don't get the right type then it may not work even for a tear so you have to be careful
you really have to go to someone who kind of understands there's a nuance even with
PRP and that's because if you use the wrong type of PRP it can actually make things worse
and the same thing with any of these technologies so you have to understand the science and not
just be a clinician and that's the tricky part about this field and Regina medicine is very dense
in that way it's not just being a doctor in a sense you're just injecting people or being a surgeon
with your hands or mechanics you also have to understand the science and basic science and a lot
of that is traumatizing to doctors because they have to memorize all these pathways in medical school
and they just want to forget about them and they don't want to review that stuff at all so
I enjoy that stuff for whatever reason so I find it fascinating and I am an interventional doctor
now and so I obviously inject people and treat them all the time with my hands but I'm also reading
all the time because I have to understand the science. Yeah and it sounds like it's the type of field
also where the science is just changing and emerging and they're new things being discovered
you know like almost on a daily basis but it's interesting that one of the knocks that I've heard
on PRP is that I'll talk to 10 different people who've gone to 10 different doctors and had PRP
treatments for you know like let's say a similar condition in knee injury or a tendon injury and
some will say it literally changed my life it stopped me from having surgery it healed everything
I'm pain free and others will walk around and basically say like I nothing like there's literally
it had zero effect is that more about some things just aren't aren't responsive or some people
aren't responsive or is it more about not properly matching the modality that's exactly what it is
that in most doctors unfortunately we're trying to medicine because it is a relatively nascent field
unless you've gone through the progression and you have a lot of experience because a lot of people
dabble in it especially surgeons they're good surgeons are great at cutting people but they're not
very good at injection and they're not very good at the basic science that's for sure and so it's
a lot of times they're trying to do something but they don't fully understand all the nuances behind it
and that's why you get all these mixed results because PRP probably shouldn't have been offered to
that patient in the first place if it was not the right indication in the right patient and there's
a lot of factors of course there's going to be cases where you think it should have worked but it
didn't and then you should have other tools hopefully in your toolbox to help that patient but
a lot of times doctors don't because they don't understand that there's a progression and how you can
kind of approach patients and use different modalities and basically I think it's more just
matching the right modality with the right patient I think that's really what it comes down to and
that's where I feel fortunate just because I've had patients from all over the world and some of
the most complex cases I've been able to obviously it's not like I got here overnight I had to
so kind of experiment a little bit and try different things on different patients and
and figure out what works what doesn't what are patterns and it was a lot of that and now we're
trying to do in a more formal settings where we're doing you know various clinical trials and
to really show the efficacy of what we're doing in real life.
Yeah are you doing clinical trials with PRP right now or focusing more on
more on stem cells so we're doing clinical trial with stem cells and all sorts of
right now and then gene therapy as well. Very cool. You know one of the curiosities that you're
talking also is and I've seen this I've had like some experience with regenerative medicine
myself and one of the things that surprised me right away is you know you'll often walk into
an office with you know either x-rays or you know like an MRI or typical scans and then you
you're sat down and somebody says well that's nice but I'm going to actually do a completely
different type of diagnostic on you and very often like the default is some sort of super high
power ultrasound which I had always sort of like looked at as well that's the quote lesser way
like that's the lesser tool to do diagnostic but it seems like ultrasound is a really essential
tool in a lot of the diagnostic side of regenerative was that just my experience or is that pretty common?
No it's it's completely true for especially for musculoskeletal like joint muscle tendon
nerves that type of stuff ultrasound dynamic ultrasound especially is often more accurate than MRIs
but it depends on the user and that's the biggest issue because MRI you can just go to machine
and anyone can do it but ultrasound so dependent on the probe and how you hold it and all these
other little finicky things so that finesse of ultrasound skills is very rare actually so you
must have gone to a good physician if they knew how to use it properly yeah what's the difference
between dynamic and sort of the way they get you to do actual movements or to like move your
shoulder do different positions because an MRI is static right you can only be in one position
really right and that's why standing MRIs are becoming more popular too because then you can
see stuff that you can't always see in the laying position and that makes a lot of sense so on the
hype side of PRP well I guess what you're saying is when people talk about PRP you're really looking
at soft tissue injuries probably around joints is certainly the prime reason yeah it's not good for
chronic degenerative stuff and I find it sad when I see patients spend money and get told that it
may help with this but in reality it wouldn't have helped and then the doctor's just like yeah it's
50-50 it may work it may not and patients just like yeah I'll try it then and but they should just
they just don't have the understanding to say like no this is very unlikely to work we should
try something else yeah and I'm very honest with my patients and I rather I rather than not do
anything at all then do something that I don't that doesn't have a high chance of success that's my
personal take on patients but not everyone's like that but PRP is not great for degenerative processes
and a lot of patients are living with degenerative conditions and looking for support in those
regards yeah and we'll be right back after word from our sponsors
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so one of the other things I've seen PRP and this feels like it falls on the hype side based on
what you're saying is um for hair growth or hair stimulation um yeah I am like definitely in the
camp where I don't have a lot of hair left but I haven't gone down that road myself at all not
interested but I've seen it promoted that way in a lot of different ways real or hype yeah no
it's definitely more hype than real so it can help in select cases if you it's it's very I would
say hit or miss and I've tried it myself personally and I mean I have good hair now and not because of
PRP but but because I've seen many other patients do it too and it tends to be so hit or miss and
I just don't recommend it anymore personally because I just don't know if it'll actually work and
most of the time it doesn't it feels like because it's just not strong enough the signal for
regeneration and for what you're trying to do and achieve is not going to be there and there's
just better technology now so I personally wouldn't recommend it for that got it okay if somebody
is exploring PRP what are a couple of good questions that they might ask or ask a physician to
sort of like see is is this person right for me and this is modality right for me yeah I think if
you should ask what type of PRP is it and do you have different types of PRP because most physicians
don't but those sophisticated ones which are are are handful in the US do have different types
of PRP and understand the nuance behind the different types so that right away will give you insight
that this physician really knows what they're doing and then the other big thing is as you said
was ultrasound guidance because there are many doctors especially surgeons who think they can
inject into a joint or attend in without ultrasound but they can't there there's been studies
showing this and or an experienced orthopedic surgeon still injects into the wrong spot in the
need joint injection 20% of the time it goes into the fat pad instead of going into the joint so it
does not matter who you are you can't just palpate it's not this isn't you know this is modern era
you need to use image guidance and the problem is it's a steep learning curve it's not an easy
thing to use ultrasound so a lot of doctors just don't want to learn. That's PRP I want to talk
about one other modality before we dive into what I think will be a rich or conversation around
stem cells and potentially even gene editing but there's one other modality that I'm familiar with
is prolotherapy which which seems like maybe that's actually the oldest modality of all of these.
It is yeah so around like since the 60s yeah. Yeah so so what is that what like what do we use it for
or what do we not use it for? Yeah the principle of that was basically using well it's really just
dextrose and saline which is just sugar water essentially and the reason they use sugar water was
they just they were I think they were just experimented different things and they found that
at when they looked at how it affected deligaments it caused proliferation which means
it's stimulating inflammation and helping things to become stronger so you don't want to promote
inflammation in certain areas for example in the joint you definitely you wouldn't want to be doing
prolotherapy just from a scientific level although there are still people doing it but again they
don't think they understand the principles of what you're just trying to achieve. If you're trying
to achieve a pro inflammatory response you want to do that generally for a muscle tear or you want
to do that for ligament instability so if the ligaments aren't stable for example we have patients
with L.A.R.S.D.D.L.R.D.L.L.R.S. Dambos syndrome who have severe ligament instability and
asthma we do prolotherapy and we use we may use a mixture dextrose and saline is a very old
technology it still works but you may have to do like six seven eight sessions what we use personally
is we use something called bone marrow aspirate and then we use something called copper peptide and
these help to stimulate collagen production proliferation and they're much stronger and much more
potent and I find people only need one procedure with it. That's so interesting yeah because I've
always heard about it in the context of anywhere from like three to ten like in a series or something
like that but it sounds like it's that's because it's using an older technology basically. Exactly
yeah and it makes sense that that wouldn't be because if that's actually encouraging inflammation
I guess because that then becomes a signal for the body to send blood and nutrients to an area to
try and like actually heal what wasn't healing yeah then you wouldn't want to do that in an area
that was already inflamed. Exactly which is why PRP if you use something called leukocyte rich PRP or
there's PRP can come in two colors and it could be golden or it can be red so the red PRP is generally
not that advantageous for most things unless it's just a chronic muscle tear but a lot of doctors
understand the difference and they'll put red PRP into a joint but that's pro inflammatory so you're
actually potentially making the patient worse which I've seen. Got it. Let's talk about the area
that I think is getting just so much attention. I would imagine you're spending a lot of time what
sounds like you're already running trials in which is stem cells because I think this is this is a
bigger more complex topic so let's start with the basic question when we're talking about stem
cells what are we actually talking about. I think the best way to explain stem cells is an analogy and so
imagine your body is like a city you have the central library where all the information is to
tell your body on the instructions on what to do and that central library think of it as your
nucleus where the DNA is those are the instructions and then you have the mitochondria which is like a
nuclear power plant and then you have all these different districts and cities in your body which
is like the organ systems and then over time what happens is the library starts becoming
damaged like the books and the instructions start becoming wrong as they replicate because
yourselves are always undergoing replication but then you have these little repair guys who come in
there and fix things those are the stem cells they their job is to come and repair DNA damage to
repair damage tissue and they're kind of these cool little architects but also construction workers
at the same time and they're able to figure out how to fix things when they go wrong but unfortunately
over time the library starts getting too much damage and the books start getting more and more
damage and the repair guys can keep up and then this is what's called genotoxicity or DNA damage
and this is what leads to aging when your DNA repair isn't the way it was when you were younger
and to put that in context when you're a child or a baby you have 200 stem cells per one cell
and then by the time you're 80 you have one stem cell per cell so it's gone down by an order of
yeah 200 basically right it's order of magnitude so it's quite a bit different so that means
that stem cell decrease in function and number it's called stem cell exhaustion is one of the most
important hallmarks of aging and that's why stem cells are such a hot area of research not just because
of their applicability to chronic pain and all this stuff but aging and longevity is one of the
hottest topics right now and so we're going to learn how can they live longer and healthier
and better lives and that's this potential is obviously in stem cells because once you understand
why we age you can understand why stem cells have so much potential. Got it so if these are so
powerful when we talk about using stem cells in regenerative medicine context then take me deeper
into that. Yeah the biggest issue with stem cells and similar to PRP is lack of standardization
so there's so many different types of stem cells and the word itself is almost meaningless because
are we talking about a mesenchymal stem cell or hematopetic or induced play potent stem cell there's
all these different types but the most important thing to understand is how do we control the stem cell
to do what we want meaning how do we almost program it in a way so that it sends the signals that
we want it to send and that's called cellular engineering and that's kind of the era we're living in
now whereas before we were kind of just taking stem cells from your body or from a chemical cord and
then we were just injecting them back in and the results have been very mixed for that and they
continue to be because there's no standardization and so although we still use the chemical core
stem cells in practice we have now engineered stem cells and engineered products that we're using
because we know better how they're going to function once you put them in the body and it lasts
for better standardization this is kind of where we're headed now and when I mentioned earlier
about that Japanese fellow Yamannaka pressing the reset button on an old cell making it young
again that's called induced play potent stem cell or IPSC and those IPSCs are kind of the holy
grill of stem cells because they can turn into any type of tissue in your body and they have the
ability to actually engraft which means they can actually regrow new tissue and this has been shown
in clinical trials with Parkinson's disease with diabetes and now there's so much research happening
for so many different organs and the sky's the limit right if you can grow any type of cell
and repair the body then you can theoretically eventually fix any degenerative condition in the body
and even aging eventually I think maybe not cured but definitely at least severely slow down
because if you can make all your cells in your body young again theoretically you could live forever
and that's a mortal jellyfish is at least for at least for 5,000 years or something ridiculous
because it can de-differentiate a cells it can make its old cells young again at will which is
kind of crazy yeah I mean as you mentioned Yamannaka and I know he was known as discovering these
as you described induced pluripotent stem cells yeah I think induced me he sort of like you
know figured out a way to create them pluripotent meaning these are some I guess then they often
start with like stem cells are just really basic cells and then yeah skin exactly right and then
find a way to literally turn them into stem cells that could then turn into whatever type of other
cell that you wanted to but that research if I remember correctly it's probably about you just
got to be about 15 years old at this point when you're almost 20 years 2006 yeah so my question is
like because you're not seeing a lot of those IPSCs in clinical we're out there and like so what's
we are now because the problem was up until now the risk with these IPSCs is because when you
coax them you're coaxing a cell basically to become young again but that has some risk with it
and the biggest risk with it is that they're essentially embryonic in nature so they can
grow into tumors or cancer and sometimes a DNA can be damaged and sometimes maybe it might turn
into something you don't want to turn it into a few point of body so learning how to differentiate
these cells into the right cell lineages and making sure the local environment you put them into
do what you want that took some time to figure out but for the most part it has been figured out
for the meaning they have figured out how to differentiate these cells into neural progenitor cells
into beta-iely cells for the pancreas into cardiomyocytes for the heart so now we have all these
different processes to differentiate these cells and there's a company that we're working with
specifically that has a technology it's their proprietary tech that prevents these IPSCs from
growing tumors or cancer it's called failsafe and it's basically a gene edit inside of the IPSCs
so if they start replicating uncontrollably if you have uncontrolled proliferation it will act
as a kill switch so meaning it'll stop the cell from dividing so you have that safety mechanism built
into it and that's the company we're using and that's the reason we partner with them is because
of that technology so we can feel comfortable putting these IPSCs into patients because we know
they have that failsafe built into it. How far are we now with actually seeing patient outcomes
with these IPSCs? Well Blue Rock therapeutic is the one that did a clinical trial for Parkinson's
and they took IPSCs but these don't have the failsafe mechanism so they there's obviously some risk
of having cancer potentially but it's probably 1% or so but obviously patients were okay to do it
and so there was 12 patients or so and they took these IPSCs and they turned them into dopamine
producing neurons and then they transplanted them via surgery into the area of the brain where they
lose the dopamine producing neurons called the basal ganglia and they actually engrafted
meaning patients were actually producing new neurons that were able to produce dopamine so
this is the holy grail right you're actually creating new tissue that's fixing the problem
instead of just masking it and these patients go into remission which is unbelievable and the dose
there's two dosing groups and the dosing group that had higher seem to have better results so
it's just amazing to see the potential though of what this technology can do and I think this is
just the beginning of the era of the IPSC era there's 40 IPSC companies now I think and they're
just exploding and it's definitely going to be a you know there's not going to be 40 companies
in 20 years from now there probably just be a few that end up having the technology and owning it
and really getting the best results but this is the field regenerative medicine that's headed towards
now yeah I mean that's amazing especially when you talk about the results in the brain like that
because I was always taught that you know you hit a certain point in life like you have X number
brain cells and yes there's neuroplasticity but that's largely about you know synapses rewiring it's
not you're not generating new neurons not generating new brain cells but sounds like what you're describing
is actually like generating new neurons exactly that's why I'm very excited about the neuro
progenitor cells that we're gonna create we're gonna create them from IPSCs and we're gonna explore
that for dementia Alzheimer's and I mean even MS there's so many different conditions you can use
this stuff for so I guess make your curiosity around that is like if we take MS or Parkinson's as an
example if there's some sort of genetic signal or maybe I'm making an assumption here if something's
happening which is basically stopping in Parkinson's case you know like dopamine generating neurons
from actually like generating dopamine anymore and then you do an IPSC intervention and all the
sudden you start generating neurons that are generating dopamine and that's which is the counter
to Parkinson's are you changing the genetics of the existing neurons or they just dying and
getting replaced by ones that actually are fixed what's actually happening there yeah no they're
actually so the old neurons are dying off essentially because they're dead you know they're not
doing what they're supposed to or they're dysfunctional they're or they're senescent meaning they
become these zombie cells right and they're not doing what they're supposed to so they're essentially
just you know and they're not being cleared up the way they should so when you put in these new cells
it changes the signaling and the local environment as well which means it helps to reduce neuro
inflammation it helps with oxidative stress and it helps with other kind of cellular hallmarks as we
talked about earlier that are associated with Parkinson's because we know that a lot of these chronic
diseases you know have all these different hallmarks so for example in Parkinson's they found that
there was a trial last year that showed that even certain gut bacteria are is linked to Parkinson's
so they got dysbiosis or having the wrong bacteria can increase your risk of Parkinson's even Alzheimer's
so there's all these other things that are contributing factors which I think ultimately are the
ones that alter gene expression so even if you have a genetic predisposition I don't think genetics
played that big of a role as compared to obviously epigenetics which we understand way more about now
and how gene expression is altered and turned on and turned off based off the environment
now that makes a lot of sense so we're really kind of talking about this one cutting edge type
of stem cell the the ender splitter potent stem cells and that's where like that's where the edge is
that's where people like you were just starting to actually do the work and the science behind it
and using it clinically but when the vast majority of people talk about having some sort of stem cell
procedure these days they're not talking about that they're often talking about you you just
cried earlier mizankamol or like fat derived stem cells what are those and what are certainly the
common use cases for those like where does that make sense yeah so mizankamol stromo cells is a
technical right nomenclature but we just call them stem cells because everyone now says that but
stromo because they have a little bit of scaffolding effect and mizankamol is just kind of an
embryological term but essentially these are multipotent cells they're not pluripotent so that's
important to remember to what they do isn't there yeah exactly so pluripotent means they can
differentiate into all three cell lineages called ectoderm endoderm and mesoderm but multipotent
just means they have what's called a trilingual differentia's capacity which means they can only
turn into cartilage fat muscle and bone really so it can't go into all the different it can't
grow new neurons or other things like that so there's much more limitations with multipotent
mizankamol stem cells as compared to induced pluripotent stem cells so the question is can we
engineer mizankamol stem cells so they have more pluripotency and that's kind of where the research
is going now if you just go to your typical doctor I guess this is where there's problems in this
field is if you go in the US they're gonna tell you you're getting a stem cell procedure but stem
cell procedures are still illegal in the US and if not FDA approved obviously that's not stopping
people from doing it which I get if I mean I understand people don't agree with them but same time
they're you know there's a big black market now for stem cells and exos and all this stuff and
it's creating some problems because it ruins the reputation of people who are trying to do follow
the rules and trying to do the good work and if you go to a doctor in Florida where they're doing
stem cells they're more than likely either offering you your own stem cells which aren't true stem
cells so you're taking your bone marrow or your fat and then they're just processing it and they're
injecting it back in those are technically committed progenitor cells which means they they've already
committed to a cell lineage and they can't actually turn into different types of tissue they're just
more reducing inflammation they're more signaling molecules than anything else and then let's just
say if they're in Florida or Florida is the most commonplace that's why music Florida is an example
where there's so many clinics that are offering this and say say you get IV stem cells or exos or
something like that and they get from a billboard cord they're usually going to be derived from
a billboard cord tissue but they're not often going to be culture expanded because culture in the
expansion is very illegal in the US and so FDA can get you can get quite a bit of trouble for that
if you're not doing it under a clinical trial it's typically that's what most people are getting
I would say for the most part are getting a billboard cord tissue or exosomes which are kind of the
soup that the stem cells grow in personally where I do most of my work is in Las Cabos, Mexico and
Dubai and Europe and Tokyo and working in the summer these are all places where stem cells are
regulated and approved and you know we can debate all day about why they're not approved but the
point is they're just not approved yet by FDA, primord so do politics and safety or efficacy
but the problem as we were saying with with these mesenchymal stem cells is that they're multi-potent
so meaning they don't really have that much pluripotencies a lot patients are thinking they're
getting these in hopes they're going to regenerate new tissue but they're not really doing that
they're just kind of reducing inflammation which just will be very helpful for chronic pain
longevity too because inflammation and chronic inflammation is a big drier of aging so they're
still they're still useful but just being very clear and transparent about what they can do and what
they can't do and to that extent we are now working with a company that has something called
MU cells, MU cells are very fascinating and this is getting a little bit into the weeds but I think
people will find this interesting because it's another Japanese technology it's called multi-linear
lineage differentiating stress enduring cells so MU's MU and MU SE MU cells are usually only 1 to
5% of the population of mesenchymal stem cells but they're responsible for most of the pluripotency
their are a new cells are pluripotent basically and they're they're stressed enduring meaning they
can survive harsh environments whereas regular stem cells to a lot of them die once you inject them
into the body and so MU cells if one of the goals of the last kind of decade of research has been
how do we increase the MU cell concentration because then we can increase the efficacy of mesenchymal
stem cells so there's there's a group that uses Japanese technology and instead of being 1 to
5% of mesenchymal stem cells they're like 70% so you have potentially like a 30X increase in the
MU cells it's going to be significantly better in terms of effect and I'm seeing this clinically
now I'm starting to use these MU cells and there was also just been incredible for chronic
inflammation and a variety of conditions got it I mean so what I'm hearing in part is like if you
live in the US yeah be careful yeah like really be super careful and ask a lot of questions
and not necessarily that any people who are who are providing services like regenerative mesenchymal
services are malintended but it sounds like just the learning curve here and the speed at which
things are developing is so fast that it takes a huge amount of effort just to like stay on top
of what's going on I'd always been sort of like before I heard about the Yamannaka cells at the
IPSC's I heard about mesenchymal stem cells and I think that's probably if anyone's talked about
or thought about it been that's what comes up and then the only options were well it's either
bone marrow drive meaning like you take a little bit of bone marrow and basically spin it out or
it's fat drive you know you take a little bit of fat from your body and drive it from that and
those cells then have the ability to differentiate into damaged tissue and in doing so heal it but
it sounds like you're saying that's not really what happens no doctor Arnold Kaplan wrote a paper
on this in 2017 I believe it was published in nature and it was basically we need to rename these
cells call them medicinal signaling cells don't call them mesenchymal stem cells because they're not
stem cells they're signaling they're essentially just doing signals that reduce inflammation they're
not really differentiating and turning into different types of tissue and in fact even if you were
to let's say isolate the mesenchymal stem cell from the fat or bone marrow and then culture and
expand them the problem is after age 40 your stem cells just like your body age and so they
undergo exhaustion which means they don't work that well and so do you really want to use your own
cells after a certain age probably not and wouldn't you rather have babies or engineered cells that are
embryonic in nature so just intuitively I think most people understand that their cells are
going to be great as what's off the pro allogeneic cells which are from donors and people sometimes
obviously are concerned about don't you have to match but with mesenchymal stem cells you don't
they have what's called low HLA antigen expression so they don't express much of the antigen
so there's no risk of graft versus host disease it's not like hematopoeedic stem cells which are
bone marrow stem cell transplants that you have in the hospital those you have to have match
but not for MSCs got it so if you do have that procedure especially in the US and you feel some
relieve it's very likely not because the tissue has regenerator been healed it's because
inflammation that the area has been reduced at least temporarily and that's probably what you're
feeling so interesting and I guess as you noted the potential ethical issues well you know I think
there've been wide debates about the use of umbilical stem cells and like people feel one way or
the other bad but it sounds like the IPSCs are kind of like they're the next generation work
around around this because you can just take anybody's skin cell and effectively turn it into
something close enough to an umbilical one right yeah no it's in fact it's probably even better than
an umbilical because it's more like embryonic I think the ethical issues often were from embryonic
stem cells because you have to take them from aborted fetuses or growing fetuses and labs and
obviously there's so many ethical issues around that plus they can cost cancer and there's but there's
that doesn't stop people from offering them there's clinics in Mexico I've seen them they offer
embryonic stem cells it's scary number one and it's dangerous and so you gotta be very careful
where you go and that's why unfortunately I think the stem cell landscape outside of the US too
is riddled riddled with people who are just taking advantage of patients and we're trying to
really educate people and just trying to do things the right way while understanding that
this is still a very new field and we have to do a lot more research to really push it forward
yeah and we'll be right back after a word from our sponsors
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and reach visit stripe.com slash tap iPhone so you mentioned the use of these the the ideas
ideas induced polar potent stem cells in things like neurodegenerative conditions more broadly what
about things like heart disease diabetes or other sort of like a chronic systemic illnesses
yeah well it turns out that all disease starts in the cell there was a good Nobel prize
laureate who said that and i think that rains true for any chronic illness so where does
cardiovascular disease start it starts in the blood vessels called the endothelial cells and
the endothelial cells become dysfunctional why do they become dysfunctional because there's all
these toxins there's poor lifestyle there's all these things that lead to the cells in the lining
of your blood vessels to start getting damaged and they can't repair themselves like we talked
about earlier as a city and that can't repair the library the way it wants and then eventually and
we think there's something called the unitary theory of aging and it's called unitary theory because
we think that the most foundational cause of cellular dysfunction and chronic disease progression has
to do with the mitochondria so mitochondria are much more than just powerhouses as we were taught
in high school biology they do a lot more than that they help to maintain tissue homeostasis
which is very important because that's entropy over time and changes in the epigenetics is what
really leesu aging and so the mitochondria become dysfunctional and that signal meaning they can't
deal with oxidative there's too much oxidative stress they can't the free radicals build up and then
that leads to inflammation, senescence and all these other kind of hallmarks of aging so for cardiovascular
disease or diabetes at a very fundamental level there still have the same kind of dysfunctional
cellular problems and if you can restore those cellular dysfunctions then you can help to treat those
conditions and that's why stem cells are almost magical sometimes because if they're done the right
way with the right dosing and especially with these engineered stem cells now they can treat a
variety of conditions and that's why it's confusing for traditional physicians and it almost looks
like sharp and I thought the Charlotte's in thing too when I got into it was like how can they
how can stem cells treat like 20 different conditions that doesn't make any sense and but then once
you understand it you're like oh it's because it's treating the underlying cellular dysfunction and
restoring the cellular signaling and the processes that are going wrong in the first place so for
example in diabetes they've done clinical trials just with bone marrow stem cells or embalequic or
stem cells so not even engineered IPSE ones and they culture expanded though and they inject them
into the pancreas and patients can get off insulin and it's in for type 2 diabetes so how is it
doing that mechanistically it's not re-growing new pancreas cells it's just because it's reducing
inflammation helping with oxidative stress helping with the talamiers helping with all these
different things that are the hallmarks of aging it's almost like you're talking about like the
magic bullet yeah well that's it kind of you know I think it's about figuring out what cell
is going to be the magic bullet but I think one day we will engineer a cell that will be the
magic bullet yeah so here's one of my brain is going awesome so curious about this if this can
literally go into your body and help with so many different things from acute things to chronic
things let's say the typical person in their you know like 40s 50s 60s or later they're going to
have a lot of different things that need remedying in their body like all at the same time how does
the stem cell like you put it into the body and the stem cells like oh I could fix that I could fix
that I could fix that but hasn't nowhere to go yeah yeah no especially so the new cells specifically
which are the subpopulation of mesenchymal stem cells so they're inside of them they seem to be
responsible for most of the homing ability so there there is a known homing ability of MSCs of
mesenchymal stem cells but the new cells are even more much more so so we think there's something
called chemokines which are released when tissues damage chemokines are signals essay to your body help
come help me and so your body mobilizes it's immune response to do that but then oftentimes that
immune response leads to chronic inflammation and that chronic inflammation is what kind of leaves
to so much degenerative processes because you get stuck it's kind of stuck in this loop and so
what the stem cells can do is go in there and they change what's called the microenvironment
and they change the cellular signaling this is called macrophage polarization which is just a fancy
word for saying we're retraining your immune system so instead of being a pathogenic phenotype
where you're sending pro-inflammatory signals you're now going to have a much nicer phenotype
where you're sending anti-inflammatory signals and so that's basically what's happening with these
stem cells when you put them intravenously throughout the body so basically as you just got like
you couldn't pick an organ and and and go directly into it but if there's like multi-system
thing you're talking about it's almost like they have these built-in homing devices to figure out
like where's the most important place to go exactly yeah yeah that's kind of in this wild I know
I read a paper a couple weeks ago and they described they had a visual of how these stem cells
go into the blood vessels and how do they home it's almost like these cells are smart and I think
that's and I think that's the conclusion I'm coming to personally based off also Michael Levine's
work who's a bioelectricity scientist and he talks a lot about that with bioelectricity but I agree
with him in the sense that they're almost like these little you know smart little things that kind
of know what to do when you put them in the right place but it's just it's all about the environment
and the environment dictates the signaling that they're going to be told and and how to know to do
the right thing depends on the environment and that's why if the micro environment has too much
inflammation or hypoxic and there's all the wrong signals being sent then the stem cells won't work
so that's why prepping the body and having the right micro environments very important for
best results yeah that makes sense I mean as you're describing that I remember talking to a physician
who's in the field at one point and they were saying that they have been injecting stem cells IV
and then using effectively shockwave therapy to induce inflammation in particular areas that
they wanted to direct the stem cells to and the stem cells would kind of find their way to them
because they'd intentionally inflame that particular area does that make sense yeah I've heard of that
I've heard of people doing shockwave or laser or other things to try to get the stem cells to go
where they want to but I think that's a crude way of doing it personally and I also don't know if
there's any published data on that I think I think you just have to engineer the cells so that they
have better homing abilities which is what we're doing now yeah right and it's almost like you're
adding inflammation to a system that's already like in the way as a way to try and like direct these
things yeah and yeah my counterargument to that also would be we know that if there's too much
inflammation the cytokines the proteins that process inflammation they can interfere with the stem
cells to do their job right yeah so it kind of defeats the whole process the last thing I want to
circle around and I think this falls at least in part under the the ospices of regenerum medicine
is gene editing I think a lot of people have read about crisper and sort of like the evolution
of the therapy made there is in your mind and in the work that you're doing does that fall under
because regenerative so regenerative medicine and the holy grail of regenerative medicine is basically
this intersection between South therapy gene editing or gene therapy and tissue engineering
okay so all three of those is kind of what's the next era of medicine and combining all three of
those in a very sophisticated way is what's going to allow us to regrow organs and fix any disease
known to man I think but especially once crisper becomes a reality you should be able to fix any
genetic defect and it's it's we're getting there we're not there yet but that's I think that's
going to definitely happen as these technologies continue to evolve yeah so in super simple terms what
is crisper was it do it's basically at a very simple level it's essentially just this bacteria
it's called the cast nine system and basically what it does is you can take any cell out of your body
and you could basically like imagine you like take scissors and you cut you cut out this code of DNA
that you don't want in there and then you can stitch it back together and then you can put it back in
and then you can change the genome in that way but the problem is with crisper is that there's
something called off-site targets and this has been the biggest issue and because people are probably
wondering why haven't we saved humanity if crisper is a real deal you know because it sounds
in theory it sounds amazing but there's there's all these off-site targets which means it edits things
that we don't want it to edit and there may be things unintended side effects and that's why it
took 12 years for one product to come out finally they finally have one I think it's for sickle cell
if I'm not mistaken you have just reading about that recently actually yeah yeah so I think that
that's the first FDA or you know or was it European approved product and so but it took 12 years
and that's only one product and it still has risks with it and so I think we're still pretty far
away from seeing this become a reality I'm not saying crisper doesn't have a lot of potential it has
a huge potential but it's it just seems like the commercial value of it's going to take a lot
longer than we thought now the technology we're working with is called mini circles and I may be
biased because I work with them but I think mini circles have a lot more commercial value they don't
have the same power capability as crisper because we can't cut out things and correct them but we
can add genes so that's what our technology can do so we can add any gene any peptide or protein
in the body up to 10,000 base pairs which is fairly big but not as big as obviously crisper can
just pretty much do anything but again the good thing about our technology is that there's no
off-site targets so what is a mini circle a mini circle is a plasmid that's derived from E. coli
a bacteria and a plasmid is just something that is used to exchange information so a plasmid is just
when you look at under a microscope it's just a circular strand of DNA and so has to name mini
circle because it's like a mini circle and you can insert whatever gene of interest you want onto
this mini circle and then you can inject it into a patient and they'll tell the local cell there
hey you have this new information so your library now has a new book and you can read that book
and they'll tell you to produce more of the peptide or protein that we insert it onto this mini
circle so you can add anything that we want on there so you can imagine there's a lot of
possibilities because we can add on any peptide and peptides are becoming very popular in the in
just general kind of public now because of ozampic but there's so many other peptides that we can
do gene therapy forms of so the first product we did was called fallostatin gene therapy and the
reason we chose fallostatin is because it's A it's been around for 20 plus years it's very well
studied and we understand all the mechanisms and B it helps to preserve muscle mass and
make and increases muscle mass and we I think we all like we said earlier muscle is definitely
the organ of longevity as Dr. Gabriol Lino says and we know that if we can help to slow down muscle
loss and or increase muscle gain we're going to help with your longevity and health span and so
that's why we chose fallostatin as our first target and so we basically it's that fallostatin
gene therapy is just an injection in your arm or stomach and it's it's not changing your DNA
but all it's doing is adding this gene and it's telling yourself to produce more fallostatin
and then it goes into your blood and it does what it does which is fallostatin is a bio-denic
peptide hormone that allows you to increase muscle mass and decreases systemic inflammation
so it's quite powerful for aging and we showed that in our clinical trial which is being
published momentarily it's available on our website if you want to read it at minicircle.io but
we are publishing it in the journal we're just deciding which journal to put it in.
Got it and is that permanent change is it short term do you do you know yet?
It's a world's first reversible plasma gene therapy so reversible meaning you can take an
antibiotic called tetracycline or doxycycline anything in that class and it'll act as a kill switch
so that's why this is a real cool technology because it's reversible and there's no other
reversible gene therapy in the world and the other cool thing about our technology is that
it's temporary so because let's just say you don't want to do it again but I mean everyone wants
to do it again after it wears off by last for 18 to 24 months so it does wear off and then you can
just get it done again so effectively if I'm hearing it right you're adding let's say your body
like there's either you don't have the gene or the gene is damaged that would let you produce
and enzyme that's necessary for you exactly maybe down the road crisper actually can swap in like
the right one or fix a broken one but what you're saying is this technology effectively says
well we can take that like whatever like the snip is and we can essentially add it in in addition
to what's there so even if the one that you have is in functioning you've now got like this
section one that's actually gonna make it generate what you need. Yeah exactly that's why it's a good
technology for conditions like cystic fibrosis where they're not making enough of a protein
right and that causes that so we have all these rare conditions that I believe we can really change
these people's lives we're we're starting out with kind of longevity and cosmetics we have
copper peptide gene therapy coming out but the reason we're doing that is because those are the
ones that are going to generate revenue so we can readvest into the more rare and more I think
ones that are going to really change people's lives. Now it's like my mind is exploding with the
potential I'm sure like you were doing this every day it's just gotta be like how do you even
folk like figure out what do I focus on because there's so many different things you could choose
so many different directions you could go. Yeah between this and cellular engineering my mind is
very entertained. Yeah and to a certain extent it sounds like that like this what you're just
talking about maybe it's not the long term thing but maybe this bridges a gap between now and when
CRISPR hits a point it's actually safe enough where you can actually make the genetic swap and
then like that last for life. Yeah exactly I could see CRISPR taking off eventually and it'll just
be unbelievable when it does yeah. Oh V either the things that we've talked about or things we haven't
talked about yet is there like one thing that you're most excited about right now? Yeah I think
the thing I'm most excited about is definitely putting the Yamanocha factors into our gene therapy
so basically the Yamanocha factors are four transcription factors that we talked about that
basically make the old cell young again but we can take those so we can take they're called OSK
and then C-NYC but that last one is the one that's associated with tear like tumors and cancer
but you can use OSK and you can still get cellular reprogramming and so not maybe as strong but you
can still make an old cell relatively young again so what we're going to do is we're going to put the
OSK into a plasma gene therapy and then we're going to we're going to do a trial where we can see
if we can rejuvenate organs and make them young again. Kind of the holy grail. Yeah pretty exciting.
Yeah that is a reason to get up in the morning to start like dive into all of that stuff.
Yeah and the one we're going to do first the organ I want to do first is the thymus because the
thymus gland is this little gland that sits around your sternum and it invulutes which means it
starts atrophying since you're basically a kid and so it just becomes smaller and smaller as you
get older and it becomes pretty useless by the time you know you're in your 60 or 70s which means
that's and that's why so many people get chronic diseases as they get older because the thymus gland
is so important for regulating your immune system. So if we can do thymus regeneration then we're
talking. Yeah that's amazing. It's so exciting. I feel like it's a cool time to be alive when it
comes to all of this stuff. It feels like a good place for us to come full circle in our conversation
as well so in this container of a good life project if I offer up the phrase to live a good life
what comes up? Peace. Being at peace with where you're at in life and being content with what you
have and with who you have it with. Thank you. Yeah thanks for having me.
Hey before you leave if you'd love this episode safe I'd also love the conversation we had with
Dr. Frank Lippman about the six pillars of well-being. You'll find a link to Frank's episode in the
show notes. This episode of Good Life Project was produced by executive producers Lindsey Fox and
me Jonathan Fields editing helped by Alejandro Ramirez, Christopher Carter crafted our theme
music and special thanks to Shelley Del for her research on this episode. And of course if you
haven't already done so please go ahead and follow Good Life Project in your favorite listening
app. And if you found this conversation interesting or inspiring or valuable and chances are you
did since you're still listening here would you do me a personal favor a seven second favor and
share it maybe on social or by text or by email even just with one person just copy the link from
the app you're using. And tell those you know those you love those you want to help navigate this
thing called life a little better so we can all do it better together with more ease and more joy.
Tell them to listen then even invite them to talk about what you've both discovered because when
podcasts become conversations and conversations become action that's how we all come alive together.
Until next time on Jonathan Fields signing off for Good Life Project.
