0:00 <b>In the past, to heal heart muscle necrosis from heart disease</b>
0:03 <b>Though there are drugs and devices to extend life</b>
0:05 <b>The ultimate solution was only one</b>
0:07 <b>Heart transplant</b>
0:11 <b>To ask the patient's body to produce new healthy heart cells to replace the damaged and dead parts?</b>
0:16 <b>This was once a myth</b>
0:18 <b>Something only God could do</b>
0:21 <b>But sometimes myths come true in laboratories</b>
0:26 <b>Imagine</b>
0:27 <b>A piece of heart tissue engineered from your own skin cells</b>
0:32 <b>Contracting perfectly</b>
0:34 <b>Expanding</b>
0:34 <b>Over and over</b>
0:36 <b>It has its own life</b>
0:38 <b>Its own rhythm</b>
0:39 <b>A rhythm that could soon mask the murmur of a failing heart</b>
0:42 <b>A repair job once possible only for God</b>
0:46 <b>How did human scientists get this ticket</b>
0:50 <b>Today</b>
0:50 <b>We will explore</b>
0:52 <b>A 20-year Japanese scientific research</b>
0:55 <b>How it finally bore fruit</b>
1:01 <b>Welcome back to YOLO</b>
1:03 <b>Your host, Bonnie here</b>
1:06 <b>I want to start the episode with a question</b>
1:07 <b>If I told you</b>
1:08 <b>Inside each of us</b>
1:10 <b>There’s actually a magic button to rewind time</b>
1:13 <b>Would you believe it</b>
1:15 <b>One that can reset our aged cells</b>
1:17 <b>Like a video game reset</b>
1:19 <b>Back to the most youthful, optimal state overnight</b>
1:22 <b>Sounds like a movie plot, right</b>
1:25 <b>Think I’m joking?</b>
1:29 <b>Today I will unravel for you</b>
1:30 <b>This Nobel Prize-stirring</b>
1:32 <b>Yamanaka factors that can upend the future of human life codes</b>
1:36 <b>Yamanaka factors and iPS cells</b>
1:43 <b>Our story begins with a Dutch grandma, Hendrikje</b>
1:47 <b>She is remarkable</b>
1:49 <b>She lived to 115 years old</b>
1:51 <b>Think about it</b>
1:53 <b>She witnessed two world wars</b>
1:55 <b>From horse-drawn carriages to space, she’s a living history book</b>
2:00 <b>But her longevity isn’t the most impressive</b>
2:02 <b>It’s when she passed</b>
2:03 <b>Her mind was sharp</b>
2:05 <b>Her physical functions still fit</b>
2:07 <b>This grandma was full of love</b>
2:09 <b>She made a decision before passing</b>
2:10 <b>Donated her body to scientists for research</b>
2:13 <b>To uncover the secret of longevity</b>
2:17 <b>Scientists were thrilled</b>
2:19 <b>Immediately began thorough research</b>
2:20 <b>In her bone marrow they found</b>
2:22 <b>A shocking fact that left everyone speechless</b>
2:25 <b>At this point</b>
2:26 <b>Let me give you a quick explainer</b>
2:28 <b>Because there are many types of stem cells</b>
2:31 <b>I used to think stem cells were one thing</b>
2:33 <b>Turns out there are many types</b>
2:35 <b>The strongest are embryonic stem cells</b>
2:37 <b>They are pluripotent</b>
2:39 <b>Can become any cell in the body</b>
2:41 <b>Like a Superman in the cell world</b>
2:44 <b>Next are multipotent stem cells</b>
2:47 <b>Like those hematopoietic stem cells in Hendrick’s bone marrow</b>
2:50 <b>They can become different blood cells</b>
2:52 <b>Like red blood cells, white blood cells</b>
2:54 <b>But can’t become skin or muscle cells</b>
2:57 <b>Then there are unipotent stem cells</b>
2:59 <b>Like the repair workers in your muscle cells</b>
3:02 <b>Specializing in maintenance work</b>
3:05 <b>Back to our story</b>
3:07 <b>What we are talking about now</b>
3:08 <b>Are those multipotent hematopoietic stem cells in the bone marrow</b>
3:11 <b>Neighbors of YOLO Street</b>
3:13 <b>Guess how many</b>
3:15 <b>Hematopoietic stem cells does a young person have in the bone marrow</b>
3:19 <b>Basically the headquarters of the cell factories responsible for our blood</b>
3:24 <b>Let’s reveal the answer</b>
3:25 <b>About 100,000 to 200,000</b>
3:27 <b>Guess again</b>
3:29 <b>Grandma Hendrick</b>
3:30 <b>died at 115</b>
3:32 <b>Inside her body</b>
3:33 <b>How many did scientists find</b>
3:35 <b>10,000</b>
3:36 <b>1,000</b>
3:38 <b>The answer is..</b>
3:40 <b>2</b>
3:41 <b>You heard right</b>
3:42 <b>TWO</b>
3:43 <b>2</b>
3:44 <b>2 commanders left</b>
3:46 <b>What is this scene like</b>
3:47 <b>Like a giant Foxconn factory</b>
3:50 <b>With thousands of production lines</b>
3:52 <b>And just 2 employees struggling</b>
3:54 <b>Keeping the whole company running</b>
3:56 <b>Before grandma passed</b>
3:58 <b>All her blood cells</b>
3:59 <b>Relied on these 2</b>
4:01 <b>Divine stem cells</b>
4:03 <b>This discovery shows us</b>
4:05 <b>Human potential is astounding</b>
4:07 <b>But on the other hand</b>
4:08 <b>It draws a cruel end line</b>
4:12 <b>Our stem cells</b>
4:13 <b>Will eventually run dry</b>
4:15 <b>When the last soldier falls</b>
4:18 <b>Is life’s train doomed to arrive</b>
4:23 <b>Arrival is the question</b>
4:24 <b>Just thinking about it makes me a bit sad</b>
4:26 <b>Maybe that’s why</b>
4:27 <b>Humans have always tried</b>
4:30 <b>To defy fate</b>
4:32 <b>Some just want to stay young</b>
4:34 <b>And visit Korea</b>
4:36 <b>Big choices</b>
4:37 <b>Like demons in Journey to the West</b>
4:41 <b>Eating Tang Monk flesh</b>
4:42 <b>For immortality</b>
4:44 <b>Eating Tang Monk flesh</b>
4:46 <b>We’re not in on it</b>
4:47 <b>But if I tell you</b>
4:48 <b>A Japanese scientist found a non-mythical way</b>
4:51 <b>Through science</b>
4:53 <b>To change cell fate</b>
5:00 <b>While the world thought</b>
5:02 <b>Aging is a one-way street</b>
5:03 <b>With no return</b>
5:05 <b>A godly man appeared</b>
5:07 <b>His name is Shinya Yamanaka</b>
5:09 <b>Shinya Yamanaka</b>
5:10 <b>A scientist from Kyoto University</b>
5:13 <b>In 2006</b>
5:14 <b>He published research like something from Dragon Ball</b>
5:17 <b>He discovered four special genes</b>
5:20 <b>Named them Yamanaka factors</b>
5:21 <b>In his honor</b>
5:24 <b>Yamanaka factors</b>
5:26 <b>Reminds you of mountain retreats</b>
5:28 <b>Or mystical fungi?</b>
5:31 <b>Definitely not</b>
5:33 <b>These four factors are not elixirs</b>
5:35 <b>They are transcription factors</b>
5:37 <b>Transcription factors</b>
5:39 <b>What are transcription factors</b>
5:41 <b>Imagine them as ultimate cell keys</b>
5:45 <b>In every cell in our body</b>
5:46 <b>Like skin or heart cells</b>
5:49 <b>The DNA is identical</b>
5:51 <b>Why do they differ</b>
5:53 <b>With unique functions</b>
5:54 <b>Because different transcription factors</b>
5:57 <b>Activate or lock specific genes</b>
6:01 <b>Yamanaka</b>
6:04 <b>What makes OKSM so powerful</b>
6:07 <b>Their combination is like a lost martial art</b>
6:10 <b>"還原靚靚拳"</b>
6:12 <b>Just inject these four factors</b>
6:14 <b>Like giving an injection</b>
6:15 <b>With a pop into a mature</b>
6:18 <b>Skin cell that</b>
6:21 <b>A miracle happens</b>
6:22 <b>The skin cell seems to reverse time</b>
6:26 <b>Losing all its features</b>
6:27 <b>Reverting to a baby-like</b>
6:29 <b>Embryonic stem cell state</b>
6:31 <b>This artificially induced</b>
6:33 <b>Pluripotent stem cell</b>
6:35 <b>Is our star today</b>
6:37 <b>iPS Cells</b>
6:39 <b>Induced Pluripotent Stem Cells</b>
6:42 <b>Induced means guided</b>
6:44 <b>What does pluripotent mean</b>
6:47 <b>It means can become anything</b>
6:48 <b>It can turn into any cell in your body</b>
6:51 <b>Can become heart, liver, spleen, lungs, kidneys</b>
6:52 <b>Can become nerves</b>
6:53 <b>Can become corneas</b>
6:55 <b>A true shapeshifter in the cell world</b>
6:57 <b>This discovery is so simple even Yamanaka</b>
7:00 <b>Said the process is like a magic microwave</b>
7:03 <b>He said it’s like putting in leftover pork</b>
7:06 <b>An old skin cell of ours</b>
7:08 <b>Press a few buttons</b>
7:10 <b>After a ding</b>
7:11 <b>Oops, out comes raw pork, not cooked</b>
7:14 <b>Turning back into raw pork</b>
7:15 <b>For any dish you want</b>
7:18 <b>Barbecue pork, sweet and sour, chops</b>
7:20 <b>Make it any way you like</b>
7:23 <b>Yamanaka knew</b>
7:25 <b>The material and the instruction</b>
7:26 <b>Skin cells and Yamanaka factors</b>
7:29 <b>Out they come, instantly transformed</b>
7:31 <b>Into iPS cells, multipurpose stem cells</b>
7:33 <b>But what actually happens in between</b>
7:35 <b>How do cells reset themselves</b>
7:37 <b>He didn’t fully understand then</b>
7:40 <b>But it’s okay, knowing how to use it is enough</b>
7:42 <b>This black box helped Yamanaka</b>
7:44 <b>Win the Nobel Prize in Medicine in 2012</b>
7:47 <b>He didn’t just find the theory of immortality</b>
7:50 <b>He also gave us a tool</b>
7:53 <b>With this cell time machine</b>
7:55 <b>What kind of future can we envision</b>
7:59 <b>First, a future without organ donation waitlists</b>
8:03 <b>Imagine</b>
8:04 <b>When any organ in our body starts to fail</b>
8:06 <b>No more need</b>
8:08 <b>To wait anxiously for a match</b>
8:10 <b>Doctors can directly use our own cells</b>
8:13 <b>To print a new, perfectly compatible, non-rejecting organ</b>
8:18 <b>Second</b>
8:19 <b>A truly personalized medical future</b>
8:22 <b>No more guessing with medications</b>
8:24 <b>New drugs can be tested on your mini organs first</b>
8:28 <b>Ensuring 100% safety and effectiveness for you</b>
8:31 <b>Most importantly</b>
8:32 <b>this future has no moral controversy</b>
8:35 <b>because everything comes from your own cells</b>
8:38 <b>completely bypasses all moral shackles</b>
8:41 <b>allows scientists to work freely</b>
8:43 <b>to fight for human health</b>
8:49 <b>but</b>
8:50 <b>dreams are always perfect</b>
8:52 <b>reality falls short</b>
8:54 <b>sounds amazing</b>
8:55 <b>can we ask doctors tomorrow</b>
8:58 <b>to reset our cells?</b>
9:01 <b>Well, young man</b>
9:01 <b>you're still too young</b>
9:03 <b>to make all these dreams a reality</b>
9:05 <b>there are two towering walls ahead</b>
9:09 <b>one wall called time</b>
9:11 <b>the other called money</b>
9:13 <b>initially</b>
9:15 <b>customizing this iPS therapy for one person</b>
9:18 <b>how long do you think it takes?</b>
9:20 <b>the answer is about six months per case</b>
9:22 <b>what about the cost?</b>
9:24 <b>about 50 million yen</b>
9:26 <b>isn’t that almost millions of HK dollars?</b>
9:29 <b>imagine this scenario</b>
9:30 <b>a six-month wait</b>
9:32 <b>may be too late for seriously ill patients</b>
9:35 <b>plus</b>
9:35 <b>millions as the entry fee</b>
9:37 <b>excludes 99% of ordinary people</b>
9:40 <b>did this great invention meant to save lives</b>
9:43 <b>end up being a life-extending game for the rich?</b>
9:47 <b>when hope of life</b>
9:48 <b>reaches an unaffordable price for us</b>
9:51 <b>how is it different from despair?</b>
9:56 <b>when people thought iPS cells were just a costly marvel</b>
10:01 <b>a hero appeared</b>
10:03 <b>to dismantle the walls of time and money</b>
10:06 <b>scientists thought of two brilliant ideas</b>
10:09 <b>the first idea is</b>
10:10 <b>a cell bank</b>
10:12 <b>Kyoto University’s team thought</b>
10:14 <b>since customizing for each person is so expensive</b>
10:16 <b>why not create a universal one</b>
10:18 <b>an iPS cell bank</b>
10:20 <b>they built an iPS cell</b>
10:22 <b>HLA haplotype bank</b>
10:24 <b>Haplobank</b>
10:25 <b>what is HLA?</b>
10:26 <b>consider it the cell’s blood type</b>
10:29 <b>to distinguish self from non-self</b>
10:30 <b>scientists specifically found HLA types</b>
10:33 <b>from people with universal donor cells</b>
10:35 <b>to create this iPS cell repository</b>
10:38 <b>how effective is it?</b>
10:39 <b>by 2023</b>
10:41 <b>the bank’s cells can match</b>
10:43 <b>about 40% of Japan’s population</b>
10:46 <b>meaning in the future 40% of Japanese</b>
10:49 <b>needing cell therapy</b>
10:50 <b>don’t have to start from scratch</b>
10:51 <b>can directly withdraw from the bank</b>
10:53 <b>cost and time greatly reduced</b>
10:55 <b>and the second idea?</b>
10:58 <b>let me ask you</b>
10:59 <b>it’s 2025</b>
11:01 <b>any plans to visit</b>
11:02 <b>before October</b>
11:03 <b>the Osaka Kansai Expo?</b>
11:06 <b>if so</b>
11:06 <b>you might see</b>
11:08 <b>an amazing exhibit</b>
11:10 <b>a piece cultivated in the lab</b>
11:12 <b>Understanding your own beating heart muscle</b>
11:14 <b>Heart muscle cell sheets</b>
11:16 <b>You</b>
11:21 <b>What are these heart muscle cell sheets for</b>
11:24 <b>They are for treating a heart disease called ischemic cardiomyopathy</b>
11:28 <b>When heart muscle dies due to lack of blood</b>
11:31 <b>Doctors can use this vibrant heart cell sheet</b>
11:36 <b>Like a patch, applied directly on the failing heart</b>
11:40 <b>Helping it restore its pumping function</b>
11:42 <b>According to Mr. Murakami, a Japanese medical reporter tracking this tech long-term</b>
11:47 <b>This therapy has completed clinical trials</b>
11:50 <b>It might apply for approval from the Japanese government as soon as Q4 2025</b>
11:54 <b>Will officially apply for approval</b>
11:56 <b>Think about this concept</b>
11:59 <b>It</b>
12:01 <b>But a major medical breakthrough that could happen within a year</b>
12:05 <b>Why can it develop so quickly</b>
12:07 <b>From lab concept to expo exhibit</b>
12:11 <b>To being ready to apply as a formal therapy</b>
12:13 <b>The answer is Japan recently opened an unprecedented hospital</b>
12:18 <b>Solving the mass production problem of iPS cells</b>
12:22 <b>Located at My iPS Manufacturing in Osaka</b>
12:26 <b>Behind this project, aside from Professor Yamanaka</b>
12:28 <b>Is also a super influential person</b>
12:30 <b>Who we</b>
12:32 <b>Uniqlo Chairman</b>
12:35 <b>Mr. Tadashi Yanai</b>
12:36 <b>It</b>
12:38 <b>But a generous donation of 500 million yen annually</b>
12:41 <b>To support the operation of this manufacturing site</b>
12:44 <b>Mr. Yanai once said a powerful statement</b>
12:47 <b>He said at a press conference</b>
12:49 <b>This isn</b>
12:51 <b>It</b>
12:53 <b>To showcase to the world</b>
12:55 <b>How Japanese companies contribute to society and humanity</b>
13:00 <b>Okay</b>
13:01 <b>So how impressive is this manufacturing site</b>
13:04 <b>Why is it a game changer</b>
13:06 <b>Let</b>
13:09 <b>Then you’ll understand</b>
13:10 <b>Previously, making induced pluripotent stem cells</b>
13:14 <b>Was custom-made for each person</b>
13:16 <b>Costing around 50 million yen</b>
13:18 <b>Equivalent to several million HKD, taking six months</b>
13:22 <b>Relying on highly skilled researchers</b>
13:26 <b>All manually done</b>
13:27 <b>Like creating a piece of art</b>
13:29 <b>Now in My iPS Manufacturing</b>
13:33 <b>They can achieve</b>
13:34 <b>Cost, aiming to reduce it significantly to about 1 million yen</b>
13:38 <b>Around 60,000 HKD</b>
13:40 <b>Wow, from 3 million to 60,000</b>
13:42 <b>And the time reduced from six months</b>
13:44 <b>Rapidly shortened to three weeks</b>
13:46 <b>Production relies on this the most</b>
13:50 <b>Its annual output can produce iPS cells for 1000 people</b>
13:55 <b>From six months down to three weeks</b>
13:57 <b>From 3 million to 60,000</b>
13:59 <b>This isn’t just a leap in numbers</b>
14:02 <b>It means iPS therapies finally overcome time and cost barriers</b>
14:08 <b>Officially moving from unreachably advanced medical treatments</b>
14:11 <b>To having a chance to materialize</b>
14:13 <b>And reach ordinary people</b>
14:15 <b>Alright</b>
14:16 <b>With banks and factories</b>
14:18 <b>What diseases can we actually treat</b>
14:21 <b>The answer is yes</b>
14:23 <b>And it’s ongoing</b>
14:25 <b>For heart disease</b>
14:27 <b>Scientists have developed heart muscle cells that can beat</b>
14:30 <b>Like a bandage</b>
14:32 <b>Applied to failing hearts</b>
14:33 <b>This therapy may apply for government approval in Japan this year</b>
14:39 <b>Another is Parkinson’s</b>
14:42 <b>Replacing brain cells with new dopamine cells</b>
14:45 <b>Also aiming to apply for approval this year</b>
14:51 <b>But its greatest progress</b>
14:54 <b>Most affects all of us</b>
14:57 <b>As we age</b>
14:58 <b>Most people will face problems</b>
15:00 <b>With our eyes</b>
15:01 <b>In 2014, it successfully transformed stem cells into healthy retinal cells</b>
15:08 <b>Implanted in a patient with age-related macular degeneration</b>
15:12 <b>An age-related macular degeneration patient</b>
15:15 <b>By last year, 2020</b>
15:18 <b>Good news for treating eye diseases kept coming</b>
15:21 <b>A team in Kobe successfully used iPS</b>
15:24 <b>iPS cells created these retinal photoreceptors</b>
15:27 <b>Transplanted to three patients with a tough eye disease</b>
15:30 <b>Retinitis Pigmentosa</b>
15:33 <b>Patients with Retinitis Pigmentosa</b>
15:35 <b>One patient showed noticeable vision improvement</b>
15:38 <b>And cells survived for a year without severe side effects</b>
15:40 <b>No severe side effects</b>
15:42 <b>Meanwhile, a team in Osaka</b>
15:44 <b>Made corneal tissue from iPS cells</b>
15:47 <b>Transplanted to four patients with Limbal Stem Cell Deficiency</b>
15:52 <b>Patients with Limbal Stem Cell Deficiency</b>
15:54 <b>Restoring their vision for normal life</b>
15:57 <b>From lab to clinic</b>
15:59 <b>iPS cells have taken nearly 20 years</b>
16:01 <b>A Nobel Prize-worthy invention</b>
16:04 <b>Step by step towards practicality</b>
16:06 <b>In the near future</b>
16:07 <b>We, who love visiting Japan</b>
16:10 <b>Might include iPS treatments in our travel plans</b>
16:13 <b>On our travel itinerary</b>
16:16 <b>We must also remember</b>
16:18 <b>Creating iPS cells is just the first step</b>
16:21 <b>How to teach them obediently</b>
16:22 <b>to become specific organ cells</b>
16:26 <b>a completely unsolved black box</b>
16:29 <b>But the completion of Osaka's MyIPS facility</b>
16:32 <b>seems like a new milestone</b>
16:34 <b>indicates we are living in</b>
16:37 <b>an era witnessing medical miracles</b>
16:39 <b>Extending healthy life until</b>
16:41 <b>our last day</b>
16:43 <b>we live with health and dignity</b>
16:46 <b>This ultimate goal of medicine</b>
16:47 <b>because iPS cells</b>
16:49 <b>seem really closer</b>
16:52 <b>This reminds me of</b>
16:53 <b>our program name YOLO, You Only Live Once</b>
16:57 <b>We used to say YOLO</b>
16:58 <b>means life is only once</b>
17:00 <b>Live it wonderfully</b>
17:01 <b>But with the emergence of iPS cells</b>
17:03 <b>might bring a new definition to living once</b>
17:07 <b>It's not about living 200, 300 years</b>
17:09 <b>but in our limited lifespan</b>
17:12 <b>live healthier</b>
17:13 <b>more quality</b>
17:14 <b>more dignity</b>
17:15 <b>Perhaps the true meaning of YOLO</b>
17:18 <b>is not the length of life</b>
17:19 <b>but the breadth and depth of life</b>
17:22 <b>And Yamanaka Factors</b>
17:23 <b>are a key to help us</b>
17:25 <b>expand the breadth of life</b>
17:27 <b>Alright</b>
17:28 <b>Today's YOLO Street share ends here</b>
17:30 <b>Hope after listening</b>
17:31 <b>you become more curious and hopeful</b>
17:33 <b>about this field full of possibilities</b>
17:36 <b>Bye Bye</b>