Cutting-Edge Regenerative Medicine for the Knees

Join us, as we explore Medical Frontiers!

Most of us take our knees for granted.

But simple everyday movements such as walking,

bending or even going up and down stairs would be impossible without knee joint.

Once the joint is damaged either by injury or aging, it can't fully recover.

And in severe cases, even walking can become difficult due to pain dramatically affecting quality of life.

However, this may all change with a promising new breakthroughs in regenerative medicine.

55-year-old Watanabe Susumu was suddenly stricken with knee pain five years ago.

I'd never experienced such severe pain before.
It would start the moment I got up in the morning.

My knee made popping sounds every time I bent it,
similar to someone snapping their fingers.

The sounds were accompanied by excruciating pain
that would stop me in my tracks.

When walking, I had to keep my right leg
straight like a stick and avoid bending it.

I could only walk at half or one-third of
the speed of the people around me.

Going up and down the stairs was especially hard.

He was diagnosed with a torn meniscus.

The meniscus is a structure inside the knee joint sandwiched

between the cartilage covering the ends of the shin and thigh bones.

Its main function is to absorb shock to the knee.

This endoscopic footage of Watanabe's knee shows the torn parts of his meniscus pressing against the cartilage.

This would cause him pain every time he walked.

Watanabe's hobby at the time was running marathons.

This put a huge burden on his knees.

I used to run 60 to 80 kilometers a month.

I think the burden accumulated, causing my injury.

There are two standard surgeries for meniscal damage.

The first one is a meniscectomy, or the complete or partial removal of the meniscus.

It ensures the torn meniscus does not press against cartilage.

This method is used 70 percent of the time.

However, the loss or reduction of the shock-absorbing meniscus causes

the cartilage to gradually wear out, and pain returns.

The other method is suturing.

But in most cases, it is unsuitable.

It involves sewing the torn parts together to encourage the meniscus to heal on its own.

But the tears may recur.

Thirty percent of patients require reoperation within 10 years.

After hearing this, I realized surgery
may not help me to recover fully.

I thought I would try rehabilitation first
to see if it would help.

He did muscle training to reduce the burden on his knee and improved his posture and gait.

But the pain didn't go away.

If a torn meniscus is not treated, it increases the burden on the cartilage, causing pain.

This is an early sign of knee osteoarthritis.

When the condition progresses, the loss of the cartilage causes the bones to rub up against each other.

This creates severe pain, which makes walking and sitting difficult.

I realized rehabilitation was not enough
to give me the results I was hoping for.

I began to think about joining the clinical trial.

At the time, a clinical trial had begun at the Tokyo Medical and Dental University

for a new treatment that doesn't require a meniscectomy.

It is a regenerative therapy using stem cells.

Stem cells can develop into different cells, such as those of the blood, organs and bones.

By taking the patient's stem cells, culturing them and transplanting them back into the body,

it is possible to replace damaged tissue.

In the trial, the patient's stem cells were used to regrow their meniscus.

We're joined by Ichiro Sekiya, who developed this treatment.

Professor Sekiya, thank you so much for your precious time today.

Thank you for having me.

And what are some of the risk factors for osteoarthritis?

Age is a risk factor. The older people get,
the more likely they are to develop the disease.

Obesity is another factor.
Also, it's more common in women than men.

The risk factor that's been drawing the most
attention is deterioration of the menisci.

In a study targeting 500 people, Sekiya found that the menisci gradually deviate

from their normal position with age.

This footage shows the meniscus in blue, the cartilage in white and the shin bone in gray.

The meniscus gradually moves outward as it loses elasticity due to aging.

This exposes the cartilage, causing it to wear out.

When the condition progresses, a tear occurs in the meniscus,

leading to an even bigger loss of the cartilage.

The pain can make walking difficult.

When the meniscus tears, it deviates even further.

Suturing can prevent tearing. But in many cases,
that's not enough to stop the pain.

We aim to regenerate damaged menisci with
transplants using the patients' own stem cells.

Watanabe joined the trial on the advice of his doctor, Sekiya.

The first step of the procedure involves inserting an arthroscope

and forceps into the knee to remove tissue called the synovium.

The synovium is a thin membrane that lines the inner surface of the knee joint.

It has a very high capacity to regenerate.

Half a gram of synovial tissue taken from the patient is chopped up into small pieces.

It is treated with an enzyme and cultured.

In two weeks, about 50 million stem cells are ready for harvest.

The meniscus is sutured, then the cells are injected to promote regrowth.

The procedure took very little time.

The collection and injection of the cells
took about half an hour each.

Neither of the steps were taxing.
My pain disappeared right after the treatment.

This endoscopic footage shows Watanabe's meniscus one year after the treatment.

It no longer appears jagged and has recovered enough for Watanabe to be able to walk.

I don't feel any pain while going about my
everyday life or doing light exercises.

I've quit running.
I try not to put an excessive burden on my knees.

I had never imagined that my knee
would have such problems.

I had always thought the knees
were quite sturdy.

But the experience made me realize
that they need care.

So, Professor, what gave you the idea to use synovial mesenchymal stem cells in treatment?

I began my research around the time it was

becoming known that various stem cells
are present in the body.

I collected tissue that was meant
to be discarded after knee surgery.

And I studied which type was
most likely to develop into cartilage.

That sparked my interest in synovium-derived cells.

And Professor, what are some of the biggest advantages for using regenerative medicine

for knee injuries and knee disorders?

Collecting the synovium is a
minimally invasive procedure.

The cells are autologous, and culturing takes just
2 weeks and doesn't require any special agents.

Therefore, the treatment is not that costly.

It doesn't require a meniscectomy,
so there is a reduced risk of osteoarthritis.

Fourteen people took part in the trial.

All of them showed an improvement in symptoms.

Sekiya plans to verify the safety of the procedure so that it can be used widely,

not just at major medical institutions.

He presented the study results at an international conference in Tokyo in July.

The response was huge.

I was afraid that in 1 year, the repaired meniscus
would be displaced again, but it looks better.

Now, he enjoys golf again.

Ali Guermazi, the founder of the conference,
has high hopes for the treatment.

The results are extremely interesting and fascinating.

I do think there is huge potential here.

This is a disease that affects several millions of people in Japan, in the US and elsewhere.

This kind of stem cells may block the progression of osteoarthritis or

even prevent the osteoarthritis from happening in patients.

So, Professor, when do you hope to put the treatment into practical use?

We've tested this treatment on many patients.

In Japan, we are working to have it
covered by national health insurance.

If the clinical trial goes smoothly and
everything goes according to plan,

that should happen in about 5 years.

We're currently doing research
with that goal in mind.

It's incredibly exciting and very promising.

I'm looking forward to it being available in the very near future.

Thank you very much.

Ligament tears are another common knee injury.

They occur most frequently during certain sports, when the knee is subject to extreme force.

The anterior cruciate ligament, or ACL, is a band of tissue that connects the thigh bone

to the shin bone and stabilizes knee movements.

In Japan, researchers are attempting to find a way to treat torn ACLs with regenerative therapy.

This treatment aims to regenerate the ligament using tendons transplanted from cows.

The research was published in a science journal in April 2022.

Until now, the standard treatment for a ruptured ACL was to give patients a tendon taken from their own leg.

But the removal of the tissue can have aftereffects such as throbbing pain, paralysis or muscle weakness.

Orthopedic surgeon Masafumi Ito is a member of the research team.

As a student, he injured a ligament in his left knee while practicing judo.

It causes a feeling of sudden weakness
and instability in the lower leg.

Some try to avoid using their leg while going
down the stairs or even walking on flat ground.

This MRI image shows Ito's knee after ligament reconstruction.

Performed 20 years ago, the procedure used a tendon taken from the back of his thigh.

He resumed judo, but did not heal enough to return to his pre-injury performance level.

The removal of tissue has adverse impacts
such as muscle weakness.

It's natural that you become incapable of
performing the way you used to.

In some activities, great force is applied to ligaments.

To withstand it, they need to be at least 8 millimeters in diameter.

But very few tissues are that thick.

Artificial ligaments made of chemical materials such as polyester are available

in case the patient's own tissue cannot be used.

But they have drawbacks.

They're foreign, so they aren't assimilated
into the joint. They eventually wear out and tear.

It's not common to reconstruct the ACL
with only synthetic ligaments.

The team focused on bovine tendons.

They're strong and thick, and eliminate the need to take tissue from patients.

The biggest problem with animal-to-human tissue transplants is rejection of the tissue.

This happens because immune cells attack foreign substances that enter the body.

Machine engineering expert Kiyotaka Iwasaki found an answer to the problem.

Animal tissue is often rejected by the
human body if it is used as is.

We can prevent this by removing
certain cells contained in the tissue,

in a process called decellularization.

In decellularization, a special solution is used to dissolve the cells that trigger immune reactions,

while leaving unaffected the materials such as collagen that form the tissue framework.

But there has been no way for the solution to reach deep inside large, thick tissue such as a ligament.

You may think the solution would soak
into the tissue if you gave it more time

or increased its concentration.

But that would destroy not just the cells,
but also the tissue itself.

This was a problem we struggled with for a while.

The solution was a device that emits microwaves.

These are the same kind of electromagnetic waves as are used in household microwave ovens.

They cause molecules to vibrate.

Iwasaki utilized this property.

He succeeded in making the solution penetrate gaps between vibrating collagen molecules,

so that it reached the cells deep inside the tissue.

He then transplanted a decellularized bovine tendon into a sheep to replace one of its ligaments.

He confirmed that the tendon was gradually encapsulated by sheep tissue.

The sheep's cells migrated into the tendon, and it developed into a ligament.

To make tendons suitable for human use, they must be sterilized, dried and preserved.

But this presented another challenge.

It was extremely difficult to sterilize living tissue.
This was a huge problem.

It took us 5 years to overcome it.

The tissue is strong and flexible.

But when dried, it loses those characteristics.

It does not return to its original state.

The solution to this problem came from a creature living in the dry regions of Africa.

The larvae of the sleeping chironomid shut down their metabolism during the African dry season.

They resume metabolic activity once the rainy season begins.

The secret behind this phenomenon is a sugar called trehalose produced by the creature.

Iwasaki tried dipping decellularized tissue in trehalose solution before sterilizing and drying it.

I put it back into water and found it had retained
its strength. It was a breakthrough moment.

We want to make decellularized tissue
available to patients as soon as possible.

We're doing this in the hope that in 10 years time,
it will have become a standard therapy.

They are planning clinical trials to verify its safety for human use and confirm possible aftereffects.

The trial is scheduled to begin in 2023.

Both treatments have a way to go until they can be put into practical use,

but they offer great promise and are far less invasive and also more economical,

and both offer great hope for knee injuries.

Today, we share easy exercises to improve knee pain.

They can also prevent knee problems by improving flexibility and strengthening the muscles.

Our instructors are a knee specialist Ichiro Sekiya and his daughter Momoko.

So what's the first exercise for our knee joints?

We begin with an exercise called setting.

Sit on the floor with your legs straight.

Tighten the muscles in your inner thighs and hold for half a second…then relax for half a second.

Do this one-second exercise repeatedly.

So how many times a week do you recommend doing this?

100 times a day.

100?

You don't need to do it in one go.
But I recommend doing it 100 times total.

The inner thigh muscles play an important role in stabilizing the kneecaps.

If they weaken, a greater burden is placed on the menisci and ligaments,

making damage to the knees more likely.

It's important to contract the quadriceps,
and to move the kneecaps a lot.

I feel like there's a little noise inside.

That's not uncommon. There's no need to
worry about it if you feel no pain.

You can easily overdo this and get hurt.
Take it easy until you get the hang of it.

Next is an exercise called calf pumping.

Sit up with your legs straight.

Keeping your feet together, move them back and forth so that your toes point toward you then away from you.

Any tightness in the back of the knees could be a sign of stiff muscles around the kneecaps.

This exercise can improve their flexibility and increase mobility of the knees.

So is it also strengthening the ligaments and the surrounding muscles?

Yes. It gives a good stretch to stiff ligaments,
muscles and tendons around the knees.

So how many times should we do this exercise?

100 times a day. Make it a part of your
daily routine, like brushing your teeth.

The third one is the hip lift.

Lie on your back with your knees bent at 90 degrees.

Lift your hips off the floor, then lower them.

Repeat this movement.

This exercise strengthens the muscles at the back of the thighs called the hamstrings.

The hamstrings are connected to the knees.

They play a crucial role in bending and straightening the joints.

Many patients with knee pain
cannot do these exercises

because they no longer have enough
muscle left to support their weight.

It's important to constantly
strengthen the hamstrings.

I recommend you do the hip lift 100 times a day.
The exercise takes 1 second, so 100 seconds total.

The three exercises together take
300 seconds. That's only 5 minutes.

Consider giving yourself 5 minutes a day
so you can do all three exercises.

It was quite interesting with the three exercises, especially squeezing the kneecap.

I've never done that before.

I noticed that there's probably a lot of different muscles that I'm not using generally.

I recommend the exercises to almost everyone
who comes to the hospital with knee pain.

They've helped many patients.

Knee injuries often result in weakened muscles,
but these exercises get them back in shape.

So thank you so much with your lovely, beautiful daughter as well.

She was such a great model.

Thank you.