Japan is at the global vanguard of regenerative medicine. By Sasaki Shigehito
The global market for regenerative medicine is now nearly ten billion dollars, and Japan is expected to be the global research and development leader.
New laws implemented in Japan in 2014 have largely shortened the approval period for regenerative medicines, making Japan the first country that can put such scientific advances into applications. Therefore, in addition to Japanese enterprises, many overseas bio-tech start-ups have established a foorprint in Japan. In the past, because of the complicated approval process, Japan was rejected, but now it’s a totally different picture.
Regenerative medicine means restoring the structures and functions of functionally damaged tissue and organs with bio-tech means. It’s a cutting-edge medical technology that uses stem cells to repair body organs or tissue by transplanting artificially cultured active cells or tissues into the human body to regenerate the damaged organs and tissues to a healthy status. As an alternative to drug therapy or organ transplant, this new technology brings hope to many patients with critical illnesses. With the development of medical technology, degenerative medicine in Japan has achieved big progress, and various regenerative medical techniques keep springing up.
The Pharmaceuticals and Medical Devices Act (PMD Act) passed in Japan in 2014 opened a green channel to the new cell therapy: once the safety and predictable effects of the products are proven, they can get approval from the competent authorities for further sales and therapeutic effect evaluations with clinical tests.
The PMD Act has shortened the approval period from the previous seven years to 2-3 years, which has even largely exceeded the timescales in Europe and America.
Regenerative technology includes: regenerative factor therapy, physical therapy that helps restore tissue or organ functions, cell regeneration therapy that inject cells of regenerative functions to human body, transplantation regenerative therapy that transplant tissues or organs that are not cell re-programmed, and regenerative therapy that transplant artificial tissues and organs that are cell reprogrammed, etc.
Among all the regenerative medicine techniques, stem cell transplantation and inductivity pluripotent stem cell techniques are the most attractive. The latter is regarded as a revolutionary achievement in regenerative medicine technology and is highly valued by the regenerative medical field. Professor Yamanaka Shinya from Kyoto University discovered and successfully cultivated inductivity pluripotent stem cells in 2006 and he was therefore awarded the Nobel Prize in Physiology or Medicine in 2012.
Later, the research group at RIKEN and other top medical centers declared that they can make retina cells through inductivity pluripotent stem cells which can develop into various cells. They successfully transplanted the cells into the right eye of a 70-year-old woman who suffered from exudative age-related macular degeneration eye problems. This is the first case in the world that has successfully applied inductivity pluripotent stem cells technique into clinical medical practice, showing Japan’s breakthrough in regenerative medicine area.
Experts say that the medical applications of inductivity pluripotent stem cells include two main aspects: Firstly, cultivating cells and tissues from stem cells inside human body like tooth, nerve, retina, myocardium, blood, liver and more and transplanting them into the corresponding parts to restore the health of the organs that are damaged or have pathological changes. Secondly, it is for the research and development of drugs targeting difficult and complicated diseases. With the inductivity pluripotent stem cells technique, medical staff now collect cells from the patient and cultivate them into stem cells, then analyze the pathogenesis in test tubes, so that they can develop effective medicines at the cells level to combat diseases. This new technique can hopefully shorten the time, reduce the difficulty and cost of developing new drugs.
Although the application of inductivity pluripotent stem cells technology into clinical medical practice has no long history, other regenerative medical techniques and studies have achieved plentiful results and brought good news to the patients. The regenerative medical technology that have already been clinically applied or under test in Japan include those targeting skin, cartilage and bone, tooth and periodontium, cornea, blood vessels at nerve end, heart, liver, kidney, nerves (end and pivot), esophagus and more.
In order to guarantee safety, the associate professor Nakayama Toshi from Tottori University use the breast cancer patient’s own stem cells to cultivate breast tissues and transplanted them into the area which had undertaken surgery excision for regeneration. This successfully made the patient’s breast recover to normal status. In the past, doctors mainly took the skin from the patients’ back and transplanted it to the excised area of the breast, which features a high risk. The inductivity pluripotent stem cells technique, however, has largely reduced the surgery risk.
Yokohama City University has developed new methods to produce cartilage by imitating the chondrogenesis of the human body. The research team collected the cartilage precursor cells of the auricle and cultured it together with endothelial cells of the umbilical blood vessel. About 48 hours later, blood vessel structures are formed in the cartilage precursor cells, as well as a stereo chemical structure of 3mm diameters. This new method of cartilage cultivation is comparatively simple without the need of using expensive growth hormone. The stereo chemical structure can also be used in transplantation experiments. The process features high safety as well.
Japan’s cutting edge medical institute joined hands with Kobe University’s hospital and developed a new method for knee cartilage regeneration with the patient’s own cells. Research personnel collected very little cartilage tissue from a young woman’s knee area who had got knee cartilage injury and cultivated them in a jelly like gel. About two weeks later, the doctor transplanted the cartilage tissue and the gel back to the knee and the damaged cartilage was regenerated. After one month’s rehabilitation, the patient fully recovered.
Meanwhile, research staff from Kyoto University and RIKEN have successfully cultivated cranial nerve cells from bone marrow cells of white rats. After one week’s experiments, nearly all the cells turn to nerve cells and one-third of them have neurotransmission substances. Experts believe that if such techniques are put into practice, it is possible to cure one of the most stubborn cranial nerves diseases, Parkinson’s Disease. This new technique is estimated to be applied to medical practices in three years’ time.
In an effort to reduce medical costs, RIKEN and Nikon co-developed a new method to produce cell membranes for transplantation usage from inductivity pluripotent stem cells with low costs and quantity production, so that the cell membrane can be applied to the patients’ body more easily and quickly. The cost is one-tenth of that previously, about 60,000 RMB.
Positive Economic Outlook
The Japanese government has made cutting edge medical technology including regenerative medicine a key pillar of “New Economic Growth Strategy,” hoping to boost the national economy by developing and applying regenerative medical technology.
At present, Japan has enhanced the research and development force in regenerative medical field including cancer, cardiovascular and cerebrovascular diseases, inductivity pluripotent stem cells, artificial skin, and cartilage, as well as other cutting-edge medical fields like nursing robots. Through improvements in the medical field, Japan hopes to lead the wide application of advanced medical technology to create more wealth and new employment opportunities.
According to the estimation of Japanese medical investigation and survey departments, the market volume of global regenerative medical products will reach 1,000 billion yen in 2020, 30 times that of 2010. But the survey points out that the product scale of inductivity pluripotent stem cells is still small. The main forces that drive the rapid development of regenerative medical market are cancer immune cell techniques and adult stem cells which exist in the body and can be divided to other cells. However, inductivity pluripotent stem cells may gain a systematic market in the 2020s.
According to the Ministry of Economy, Trade and Industry, the global market scale of regenerative medicine was 340 billion yen in 2012 and it will reach 17,200 billion in 2030.