<Health>

Will the Pluripotent Stem Cell Prove to become a New Growth Engine?

Race for stem cell research begins in Japan, U.S., and European countries

STRI from South Korea starts preclinical with its pluripotent stem cell without side effects

Weekly Donga

Mar 2, 2016

Over a decade have passed since Professor Hwang Woo-suk’s famous stem cell scandal involving a forged paper created a nationwide uproar. The Korean society was filled with distrust and anxiety with anything that involved stem cell. The scandal was even recreated into a movie, The Whistleblower in 2014.

Yet we must make sure that Professor Hwang’s incident shouldn’t be used as reason to deny the epoch-making medical advances from the stem cell in its entirety and deprive of future and tomorrow from those suffering from rare diseases. Many scientists have insisted that this unfortunate incident be taken as a lesson to bring our advances in stem cell research and development to a next level.

Japan wins Nobel Prize for its induced pluripotent stem cells (iPSc)

Putting behind still suspicious eyes, many start-up companies and research institutes have made remarkable strides in their stem cell research. “Beyond the wall of distrust in stem cells research lies hope and future of those suffering from rare diseases…” remarks Lee Kye-ho, Chairman of STC Stem cell Treatment &Research Institute (STRI). He continued, “Pluripotent stem cells free from side effects and ethical controversy will serve as a new growth engine to drive the next generation economic hegemony.”

While the South Korean society stayed blue for the past decade following the stem cell scandal, the world stayed busy making strides in their stem cell research and development. World stem cell therapy market is growing at 7.6% annually. Market is expected to grow from 3.6bil US$ in 2012 to 5.3bil US$ this year. Albeit the ethical controversy, the U.S. and E.U. is opening up its regulations on embryonic stem cells to encourage research & development for cell therapy.

Already in 2004, the U.S. government has set up the California Institute of Regenerative Medicine(CIRM) and invested 3bil US$ for stem cell research. In 2009, the Obama Administration removed restrictions on federal support for stem cell research including embryonic stem cells. With the 7th Framework Program(2007~2013), EU launched the stem cell research project participated by 8 nations and 11 research institutions. 50 million Euros or 10% of its total budget on science was put into stem cell research.

It was none other than Japan who made greatest strides in stem cell research during the past decade. In 2012, Professor Yamanaka Shinya from Kyoto University won the Nobel Prize in Physiology or Medicine with his induced pluripotent stem cells(iPSc)

Although application for Professor Yamanaka’s research is limited to its applied studies and has a long way to go before commercialization, it has become an iconic future for Japan’s stem cell research. Professor Yamanaka owes his outstanding achievement to no other than the Japanese government and people.

In November 2014, Japanese government and the assembly passed the Regenerative Medicine Safety Act that allowed each hospitals to treat its patients using stem cells cultivated by individual medical enterprises. Of course such enterprises and hospitals will need relevant licenses by the government. According to the Regenerative Medicine Safety Act, new drugs in the regenerative medicine category may be commercialized upon confirming its safety and further become subject to additional subsidy for ongoing clinical. This has enabled even the start-up companies and smaller research institutions to also work in stem cells.

In order to encourage development of stem cell therapy for commercial use, the Japanese government revised its Pharmaceutical Law to enable health early sales authorization as well as apply health insurance benefits for stem cell therapy. With the revised Act, cell therapy will be allowed for public use upon meeting standards for Stage I. Clinical in addition to receiving health insurance benefits. This will be a major move forward compared to Korea where Stage III. Clinical will be needed before cell therapy goes out in the market.

STRI develops world’s first pluripotent stem cell without side effects

Japan’s Ministry of Education, Culture, Sports, Science & Technology announced that it will support up to 3 billion Japanese yen annually for the coming decade. Beneath Japanese Government’s such decision lies its ambition to dominate the field of regenerative medicine, the new growth engine to feed the next generation world economy.

Japanese MNCs are another big fans of stem cell research and development. In spite of the fact that Professor Yamanaka Shinya, the founder of iPSc himself admitted “there’s a long way to go before commercialization,” Japan’s leading companies are in a race to support his cause, investing billions of dollars. Japan’s Fuji Film acquired U.S. Cellular Dynamics, the iPSc manufacturer and further announced its plan to establish a subsidiary to develop, manufacture and sell iPSc derived stem cells.

Others include Japan’s biotechnology company Reprocell who is also an emerging star in the U.S. Established in 2003, Reprocell researches and develops embryonic as well as iPSc. Its other businesses include using iPSc derived cells for cell supply and drug screening on top of supplying reagents for bio and pharma companies. Japan’s leading cosmetics manufacturer Shiseido has set forth in a joint research to resolve hair loss using Professor Yamanaka’s iPSc. Another cosmetics manufacturer Kose is making strides in its anti-ageing research using the iPSc.

Amidst such robust advances made around the world, where does South Korea lie in its stem cell research? Since Professor Hwang Woo-suk’s scandal, South Korean scientists have put their emphasis on adult stem cells NOT embryonic stem cells. In 2014, 391 and 86 papers have been published in adult and embryonic stem cells respectively. It is 8th and 7th in worldwide ranking.

Advances in iPSc research also look promising. South Korea stands at 8th globally, publishing 26 papers in iPSc last year. Although still far behind the U.S. (310 papers) and Japan (105 papers), young scientists are fiercely catching up. South Korea is showing remarkable strides in patents registration. During 2010~2011, South Korea applied for 65 and 21 patents in the field of adult and embryonic stem cells respectively (At 3rd and 4th globally). In the study of iPSc, South Korea issued 9 patents, following up to the U.S. and Japan. In 2015, the South Korean government spent 81.2mil US$ in stem cell research and development and announced its determination to resurge as a world stem cell leader.

Noteworthy is STC-nEPS(newly Elicited Pluripotent Stem Cells without side effects by natural compound), world’s first stem cell without side effects, discovered by STR(STC-Stem cell Treatment & Research Institute), South Korea’s leading stem cell research institute.

As Professor Han Ho-sung of Seoul National University Bundang Hospital, famous for his laparoscopic surgery for liver cancer is preparing to go into pre-clinical using STC-nEPS. According to STRI, STC-nEPS uses mesenchymal stem cell separated from the umbilical cord, fat, bone marrow and cord blood tissues as source. It is then treated with small molecules (STC-f002) extracted from natural compounds to induce its pluripotency. This technology is unique to SRI and patented globally. (For more, refer to a box interview)

“We were able to induce pluripotency without any artificial manipulation and it overcomes all existing limitations including side effects from iPSc and ethical controversy involved with embryonic stem cells,” remarked Lee Kye-ho, Chairman at STRI. He continued, “Autologous as well as allogenic stem cells may be used and it is free from side effects and autoimmune rejection responses. Furthermore, with our technology which enables its mass production, we anticipate a major change in tomorrow’s medical paradigm including those in cell therapy as well as new drug development.” STRI applied for 32 patents in 146 countries (among which seven have been registered in Korea) with their pluripotent stem cell without side effects STC-nEPS and its derived cells – pancreatic beta cell, neurocyte, hepatocyte, chondrocyte, osteoblast and adipocyte.

“It won’t be too long before we are able to cure rare diseases, enable down ageing and recreate every human tissues and organs using STC-nEPS, the pluripotent stem cell without side effects,” says Lee Key-ho, Chairman of STRI. He continued, “We’re now in the process of discussing joint collaboration with world renowned research institutes buy cialis overnight delivery.”

STRI has been cooperating with Seoul’s 97.7 B&H Clinic, treating rare diseases and offering down-ageing services using (cord derived) mesenchymal stem cells. Remarkable advances have made in the areas including alopecia, CNS, brain damage, facial nerve palsy, and spinal injury. Wang (28, living in China’s Jilin Province) suffering from alopecia was able to see her hair grow back after stem cell therapy at the 97.7 B&H Clinic.

Stem Cell Therapy creates miracle

“For the past ten years, I’ve sought every possible means with the hope that my hair will grow back but no luck. However by visit to the 97.7 B&H Clinic in Seoul last year allowed me to dream like a girl once more…” remarked Wang. She continued, “At first I didn’t have much hope but it changed my life. The response wasn’t immediate after the therapy but when I was about to give up, the stem cells inside of me created a miracle. I hope stem cell research will make more meaningful advances to give hope to many like myself, suffering from rare diseases.”

Collier(35) living in Florida, U.S. is on a wheel chair ever since he fell from a building when he was 28 and suffered a spinal cord injury. However since his stem cell therapy at the 97.7 B&H Clinic last year, he’s showing small but meaningful improvements including recovery of his senses.

As an organ that connects the brain and the body inside the spinal canal, a spinal cord takes control of the neural pathway. Without self-regenerative ability, it loses all or part of the sensory or motor functions from the damaged part and downwards, once damaged. No actual cure has been identified so far and efforts stayed within the boundaries of minimizing second injury in forms of surgery, therapy or rehabilitation.

As a father of three and husband when the accident happened, Collier was determined to get better and tried everything in his power. However there wasn’t a doctor who gave him a positive response. In 2010 he flew to Korea to try the stem cell therapy however it was still new to him and full of anxiety, he gave up after two therapies and returned home. Hearing his story by coincidence, 97.7 B&H Clinic offered Collier a second try, with all costs to be paid by the Clinic and Collier flew to Seoul once more with his wife.

Following six therapies at the 97.7 B&H Clinic last December, Collier was able to experiences little changes. “When he first visited, Collier had no senses with paralysis of his lower body due to spinal cord injury. However after the treatments, he was experiencing senses – i.e. pain and tickling. We believe this is a sign that his nerves from the descending tract as well as the ascending tract (that connects from the brain and spinal cord and vice versa) are slowly coming back,” commented a STRI researcher. He continued, “It’s a pity that Collier is so far away and unable to get regular treatments. However if he continues, even at longer term intervals, we’re certain that his conditions will show remarkable progress.”

“97.7 B&H Clinic gave me a detailed explanation on the therapy which included showing of the live stem cells immediately upon injection,” said Collier. He continued, “Stem cell therapy was no longer alien to me with the doctor and staffs’ heartfelt caring and efforts. These days, I work on rehab and sometimes search the internet hoping there’s new advances in stem cell therapy. I hope to return to Seoul soon for my follow up treatment.” Collier expects to be back in Seoul this June.

<Interview-1>

 

Lee Kye-ho, Chairman and Founder of STC Group

 

Aiming for the Nobel Prize with STC-nEPS, pluripotent stem cell without side effects

‘Contributing to the mankind with cell therapy made from a righteous mind’

Such is a belief of Lee Kye-ho, Chairman of STRI (STC Stem cell Treatment &Research Institute) and the institute’s mission. As such, vision of STC Group, established in 1989 is also Soul, Treatment & Cell. We met with Chairman Lee to hear how he discovered STC-nEPS(newly Elicited Pluripotent Stem Cells without side effects by natural compound), the pluripotent stem cell without side effects.

‘Contributing to the mankind with cell therapy made from a righteous mind…’ How did you come up with such belief?

My father who spoke about your commitment to your country and the mankind and it carried on to me. STC Group has been working on stem cells, new drugs, agrosciences and gene studies. With a mission of contributing to the mankind with our cell therapy, we hope to do our very best in every steps we make.

How did you first come up with STC-nEPS?

While discussing on limitations and side effects of the iPSc developed by Japan’s Professor Yamanaka Shinya of Kyoto University with Dr. Alex Lee’s team at STRI, we tried inducing pluripotency from a mesenchymal stem cell without using any artificial manipulation. This led us to STC-nEPS, a pluripotent stem cell without side effects.

We induced pluripotency by treating the source(MSC) with small molecules(STC-f002) extracted from a natural compound. C-Myc, indicator for occurrence of tumor showed an even lesser figure even when compared with cord or adipose derived mesenchymal stem cell, which shows no occurrence of tumor. This is how we concluded there was no chance of a cancer outbreak which was validated in a (mouse) vivo test which continued for over 16-weeks.

I believe STC-nEPS is a discovery rather than a development. Answer lies in nature, created by God and the role of a scientist is to ‘search.’ Role of us scientists will be to work hard and keep searching so that God may grant us the glory to service for this mankind.

How can we apply the STC-nEPS, the pluripotent stem cell without side effects?

(Dependent on the per country regulatory environments…) STC-nEPS or the pluripotent stem cell without side effects may be applied on human body immediately. Cell therapies for rare diseases and down-ageing purposes will be our primary target.

STRI successfully differentiated its STRC-nEPS, pluripotent stem cell without side effects, into a human pancreatic beta cell, hepatocyte, neurocyte, osteoblast, chondrocyte and an adipocyte. Using the same our next step will be to work on recreating every human tissues and organs.

Furthermore, pluripotent stem cell STC-nEPS showed superior differentiation efficacy when compared with the adult stem cells (Whereas adult stem cells showed 50%, STC-nEPS showed 90% efficacy during the same period). With its ability to differentiate into all human organs, STC-nEPS is also expected to show a superior treatment efficacy for various rare diseases.

Where do you expect to go from here?

Using the STC-nEPS derived hepatocyte, we’re expecting to run a joint preclinical with Seoul National University Bundang Hospital, locally. At the same time, we’re working on differentiating into different human organ cells including the keratocyte, retinal epithelial cell, and the cardiomyocyte. I believe that the pluripotent stem cell without side effects STC-nEPS will contribute to down ageing and treating the rare diseases to ultimately give us a Nobel Prize.

Cell therapy using cultivated autologous cells will be immediately applicable in places including Japan and the State of Texas. EU nations also grant conditional approval for emergency purposes and treatment of rare diseases. STC-nEPS, based on cultivation technology will be immediately applicable on human body in those regions however restrictions are still high in South Korea.

In 2015, Sanofi signed a 3mil Euros deal up front with Evotec to collaborate on cell-replacement therapies for diabetes. The two companies will work together to turn human stem cells into beta cells, which produce insulin in the pancreas to regulate blood sugar. With research progresses, as much as 300mil Euros will be paid over the coming years. I believe the pluripotent stem cell without side effects or the STC-nEPS is a true model of creative economy. Border, race and religion will no longer reign in this 21st century and it will be value what moves us in this free economy.

I believe it is time we invest in future values driven by creative thinking.

<Interview-2>

Han Ho-sung, PhD, MD

President of the Cancer Center, Seoul National University Bundang Hospital

“STC-nEPS, is expected to change the paradigm in cell therapy”

Seoul National University Bundang Hospital to undergo preclinical to develop cell therapy for liver cirrhosis, using STRI developed STC-nEPS.

What will be the view of a surgeon who specializes in cell therapy? Leading expert in laparoscopic surgery for liver cancer, Professor Han Ho-sung, President of Seoul National University Bundang Hospital answered us using two words, “New Hope.”

Professor Han already carried out country’s first high-definition stereoscopic telesurgery many times and more recently he proved to the world that laparoscopic surgery for liver cancer (compared with laparotomy) actually led to more positive outcome in terms of the patient’s quality of life and comparable outcome.

We asked Professor Han on the value of stem cell research while he awaits a preclinical using STRI developed pluripotent stem cell without side effects or the STC-nEPS.

What will be significance of stem cell research and development?

Modern science suggests no other alternatives to organ regeneration other than transplantation. This is a problem. Too many patients waiting but too few organs to share.

Only if those suffering from rare diseases involving the liver, kidney or pancreas are able to replace their organs or undergo cell therapy as outcome of stem cell research & development, this is new hope. If we are able to replace organs developed using a pluripotent stem cell, this will be a phenomenal change that will be making a new paradigm in medical history. Treating diseases will be about removing the source of the illness and in turn lead to enhanced quality of life for mankind.

Stem cell therapy seems to be making amazing strides…

Life isn’t easy for those suffering from rare diseases and economic difficulty makes it worse. Such pain is also shared by family and friends. With the advances in stem cell therapy, it is expected that those suffering from rare diseases and their family members will be able to return to their happy, healthy lives.

How would you assess local stem cell technology?

How could the government support in this matter?

Stem cell technology has boundless opportunities. South Korea joins the world in support and investment for this area.

As seen from other countries, advances in bio industry and leading bio institutions will become enabled only with government support. That is how the stem cell industry will grow to become a national infrastructure.

I hope as a country we can become more aggressive towards stem cell research and clinical which will in turn give rise to outstanding scientists and researchers in South Korea.

I heard you’re preparing for pre-clinical using STRI developed pluripotent stem cell without side effects or the STC-nEPS.

We will be using STC-nEPS derived hepatocyte to develop cell therapy to cure liver cirrhosis. We expect this research to bring forth a world standard outcome to ultimately propose to us a whole new paradigm in cell therapy.

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