Cell therapy, also known as stem cell transplantation therapy and biological therapy, refers to the transplantation or infusion of normal or bioengineered human cells into the patient's body. The newly imported cells can replace damaged cells or have stronger immune killing. function, so as to achieve the purpose of treating diseases.

At the end of October 2021, Vertex, the world's top pharmaceutical company, released the latest clinical trial data on the allogeneic stem cell therapy VX-880 in the treatment of type I diabetes. On the 90th day of receiving VX-880 treatment, The patient's insulin production function was restored, daily insulin requirements were reduced by 91%, while glycemic control was significantly improved and well tolerated. This is the first demonstration that stem cell therapy can restore islet cell function in patients with type 1 diabetes.

On April 13, 2022, the internationally renowned medical journal "Nature Medicine" published the latest research results of Professor Deng Hongkui from the School of Life Sciences of Peking University, revealing the experimental progress and research results of stem cell therapy for diabetes.

On the evening of April 13, the international academic journal "Nature" published an important breakthrough in my country's stem cell preparation technology. The team of Professor Deng Hongkui from Peking University reported for the first time in the world the use of chemical small molecules to change human somatic cells and obtain a new generation of stem cell preparation. The technology can be used to treat major diseases such as diabetes, severe liver disease, and malignant tumors in the future.

These series of clinical research results have rekindled people's expectations for stem cell therapy. In the face of the current situation where no stem cell therapy has been approved by the FDA, can Chinese stem cell technology take the lead in the field of stem cells? Can stem cell therapy really be used by humans and benefit more patients?

“born” with aura: bearing infinite hope

Stem cells are a type of cell population with self-renewal and multi-directional differentiation potential, mainly derived from umbilical cord blood, bone marrow, peripheral blood, embryos and dental pulp, etc. complex tissues and organs.

Stem cell therapy refers to the replacement of diseased tissues and organs with stem cell-derived tissues or organs, and is applied to diseases that cannot be cured by traditional medical methods such as spinal cord injury, diabetes, and ischemic heart disease. The stem cell medical industry is an entire industry including stem cell extraction, stem cell storage, stem cell product development and stem cell therapy.

Since hematopoietic stem cells were used in the first bone marrow transplant in 1968, the application of stem cell medical technology has begun to develop rapidly.

In 1998, American scientists discovered human embryonic stem cells (ES) that could be isolated and cultured in vitro, but ethical issues were once questioned.

In 1999, stem cell therapy was listed by Science as the top ten scientific achievements of the year because of its bright therapeutic prospects.

In 2006, Shinya Yamanaka, a professor at Kyoto University in Japan, obtained induced pluripotent stem cells (iPSCs) for the first time through genetic technology, which was not only expected to avoid ethical issues, but also won the Nobel Prize.

Since then, stem cells have gradually become a hot spot in the field of biomedicine, and countless scientists at home and abroad are scrambling to study the physiological mechanism and application prospects of stem cells in various fields of medicine.

Simple diagram of stem cell therapy

At present, stem cells are divided into embryonic stem cells, adult stem cells and iPS stem cells. Among them, embryonic stem cells are derived from early embryos and have strong growth and differentiation capabilities, but they are faced with a series of ethical issues, and the regulations and policies of various governments on related research have been ups and downs. In addition, the allogeneic origin will produce a large rejection response, and some of the cell lines will change shape during the process of subculturing.

Adult stem cells are relatively easy to obtain, there are no ethical issues, and there is no histocompatibility. Theoretically, the risk of tumorigenesis is low. However, the isolation and in vitro culture of adult stem cells have not yet been fully resolved. In some genetically defective diseases, genetic errors may appear in patients, and such stem cells are not suitable for transplantation.

Since the discovery of iPS stem cells, due to their unique advantages in stem cells, it has immediately become a hot spot in the field of stem cell research. Although the iPS stem cells generated after gene reprogramming avoid ethical issues and have no histocompatibility issues, the low reprogramming efficiency and the possibility of inducing mutations are still difficult problems for scientists.

From the current point of view, stem cell therapy technology is not mature, but due to its self-renewal ability, multi-directional differentiation potential and high proliferation ability and other biological characteristics, people have placed extremely high treatment expectations. Clinical studies have been initiated in various disease areas such as metabolic diseases, immune system diseases, cranial nerve diseases, neurodegenerative diseases, malignant tumors, and digestive organ diseases.

Chaos: The disorderly “God-making movement”

Although the "universality" of stem cells has driven the tireless research of the scientific research and medical fields, it has also become a gimmick for unscrupulous businesses and enterprises to make money. In China, the scam of "100,000 yuan per injection of stem cells" and the proliferation of so-called stem cell treatment centers from tertiary hospitals to beauty salons and small clinics all made people lose confidence in stem cell therapy.

The top international journal Nature has twice reported on China's stem cell chaos. Three months after China's Ministry of Health stepped up efforts to ban the clinical use of unapproved stem cell treatments, a survey showed that some domestic companies Or the clinics that still charge patients thousands of dollars for treatments that promote treatments for serious conditions like Parkinson's disease, diabetes and autism on their websites and attract thousands of overseas medical tourists.

Even in 2012, Feng Shiliang, member of the National Committee of the Chinese People's Political Consultative Conference and director of the Diabetes Treatment Center of Liaoning Province, quoted a limerick to describe the management problems of the stem cell industry in the proposal of the National Two Sessions: "Science and technology departments are striving to get ahead" encouragement "Doing", the health department closes its eyes "don't let it do it", the drug regulatory department has its eyes on the United States and "looks at it", scholars and experts advocate the belief "daring to do it", and business owners seek benefits and avoid disadvantages. Dizziness & rsquo;, medical institutions chasing fame & lsquo; stealing & rsquo; & rsquo; beauty institutions ’ nonsense & rsquo; swindling & rsquo;, tens of thousands of patients are guinea pig & lsquo; money & rsquo; ”

So far, the Ministry of Health and the State Food and Drug Administration have changed from standardized rectification to a complete suspension of stem cell drug research and development. From 2004 to 2012, all 10 new stem cell drug registration applications accepted by the Drug Administration have been cleared, and stem cell drug development has returned to origin.

Rebirth: The third revolution in human medical history

Even with the chaos, people's enthusiasm for stem cell therapy research cannot be stopped. In addition to the introduction of normative and regulatory policies, since 2015, various national ministries and commissions have successively issued a series of policies to support the research and development and transformation of stem cell technology. and technical guidance documents, aiming to promote the research and development and clinical transformation of stem cell technology.

In 2015, my country's first normative document for the management of stem cell clinical research, "Notice on the Filing of Stem Cell Clinical Research Institutions" was issued;

In 2017, the National Development and Reform Commission issued the "Thirteenth Five-Year" Biological Industry Development Plan, which pointed out the development of stem cells and CAR-T cell immunotherapy and other biological treatment products; at the same time, the "Thirteenth Five-Year" health and The Special Plan for Health Science and Technology Innovation also clearly calls for strengthening research on key technologies such as stem cells and regenerative medicine, immunotherapy, gene therapy, and cell therapy

In 2018, the State Intellectual Property Office issued the "Catalogue of Key Intellectual Property Support Industries (2018 Edition)", which clearly listed stem cells and regenerative medicine, immunotherapy, and cell therapy as key national development and urgently in need of intellectual property support. One of the key industries;

In 2020, the Ministry of Science and Technology issued the "Notice of the Ministry of Science and Technology on Issuing the 2020 Project Application Guidelines for Key Special Projects such as the National Key R&D Program "Stem Cell and Translational Research", with a total national allocation of 240 million yuan. At the same time, the Drug Evaluation Center of the State Drug Administration organized the drafting of the "Technical Guidelines for Clinical Trials of Human-derived Stem Cells and Derivatives of Cell Therapy Products (Draft for Comment)", with a view to providing assistance for drug R&D registration applicants and drug clinical trials. The investigators of the trials provide more targeted advice and guidance.

On February 9, 2021, the National Health and Medical Commission released the "Reply to Recommendation No. 4371 of the Third Session of the Thirteenth National People's Congress". It is clearly stated in the reply that our commission has always encouraged and supported the research, transformation and industrial development of stem cells and immune cells.

On May 10, 2021, the Ministry of Science and Technology of the People's Republic of China issued the "2021 "Stem Cell Research and Organ Repair" National Key Research and Development Special Application Guidelines. In order to implement the relevant deployment arrangements for national scientific and technological innovation during the "14th Five-Year Plan" period, the National Key R&D Program has launched the implementation of the "Stem Cell Research and Organ Repair" key project.

In April 2022, the Ministry of Science and Technology of the People's Republic of China released the 2022 annual project application guidelines for the national key research and development program "Stem Cell Research and Organ Repair".

According to the previously issued application guidelines (draft for comments), the 2022 guidelines focus on stem cell fate regulation and mechanisms, the occurrence and aging of stem cells and organs, in situ regeneration of organs and their mechanisms, complex organ manufacturing and functional remodeling, 5 key tasks including stem cell-based disease models are deployed. Among them, the research on the intervention technology of stem cells and organ aging is one of the key directions.

On May 10, 2022, the plan at the national level will increase! The National Development and Reform Commission issued the "14th Five-Year Plan" for Bioeconomic Development to promote the standardized development of new technologies such as stem cells and immune cell therapy.

With policy support, stem cell research has shown bright prospects, and its related clinical trials have sprung up like mushrooms after a rain.

2022 domestic stem cell clinical research and development status data, so far, 21 new stem cell drug applications have been approved for clinical trials in my country, and more than 30 new mesenchymal stem cell drug clinical trial applications have been accepted. There are 140 registered stem cell clinical research institutions in China, and 111 stem cell clinical research projects have been approved and registered.

Among them, Tianjin Angsai has been engaged in the research and development of stem cell drugs since its establishment in 2004. Its mesenchymal stem cells for injection for the treatment of acute respiratory distress syndrome and acute-on-chronic (subacute) liver failure have entered the IND stage ;

In addition, Han's United Group has a total of 6 new stem cell drug clinical trials approved, one of which is "Highly Active Human Umbilical Cord Mesenchymal Stem Cell Injection"”Phase I/IIa clinical trial approved by the French Food and Drug Administration (ANSM) for the treatment of “severe lower extremity ischemia”;

The "Human Dental Pulp Mesenchymal Stem Cell Injection" declared by Beijing Sanli Heze Biotechnology Co., Ltd. for the treatment of periodontitis has also obtained the implied permission of the CDE clinical trial,

The "ELPIS Human Umbilical Cord Mesenchymal Stem Cell Injection" declared by Huaxia Yuan Cell Engineering Group Co., Ltd. for the treatment of moderate and severe chronic plaque psoriasis has also been approved by the CDE clinical trial model. Stem cell therapy is advancing rapidly.

Across the world, as of May 2022, more than 8,100 stem cell-related clinical studies have been registered on the ClinicalTrials website in the United States, including 4,026 cases in the United States, 1,923 cases in Europe, and 657 cases in China, second only to the United States and European countries. In foreign countries, according to incomplete statistics, 18 stem cell therapies have been approved for marketing, of which 10 meet the definition of drugs. And foreign companies that are currently concentrating on stem cell therapy are still flooding in, including Mesoblast (MESO), Osiris (OSIR), Pluristem (PSTI), Athersys (ATHX), Vericel (VCEL), BrainStorm (BCLI), FCB -pharmicell, medipost, anterogen, etc.

18 approved stem cell therapy products, (Photo source: National Health Products)

Analysis of domestic upstream and downstream industry chain

After years of development, China's stem cell medical industry has a certain industrial foundation. From upstream stem cell storage, midstream drug development to downstream clinical treatment, a relatively complete stem cell industry chain has been formed. Among them, the upstream is the most mature link, and the middle and lower reaches still need to be further expanded. Relevant businesses are mainly concentrated in the upstream, while most of the midstream and downstream businesses are currently in the clinical trial stage or market experiment stage.

The main ones in the upstream of the industry chain are stem cell collection and storage companies. Cell storage stores APSC pluripotent cells in cells for a certain period of time through a certain method to ensure that the function and activity of cells are not significantly affected. The main representative companies include: Tianjin Cord Blood Hematopoietic Stem Cell Bank of Zhongyuan Xiehe, China Cord Blood Bank of Jinwei Medical, Shanghai Cord Blood Hematopoietic Stem Cell Bank of Shanghai Stem Cell Technology Company, Boya Stem Cell Mesenchymal Stem Cell Bank of Jiangsu Province, Guangdong Provincial umbilical cord blood hematopoietic stem cell bank and Shandong human umbilical cord mesenchymal stem cell bank, etc.

The midstream of the stem cell industry chain is a stem cell proliferation and drug research and development enterprise, mainly engaged in technology research and development, including stem cell proliferation, stem cell drug research and development, laboratory processing supporting products (such as detection reagents), etc. Zhongyuan Xiehe, Boya Holdings, Kyushu Group, AVIC Biology, Maijian Biology and other companies are involved in this business.

The downstream consists of institutions that carry out stem cell medical treatment, mainly tertiary hospitals. At present, stem cell therapy can be used for disease treatment in the fields of repairing tissue cell damage and replacing the function of damaged cells; using in vitro cultured and expanded stem cells to cultivate human tissues and organs for organ transplantation and bioremediation of autoimmune diseases. In addition, in the field of consumer-grade applications, stem cells can also be used for medical cosmetology to delay cell aging.

In addition, as the industry matures and develops, a number of companies have begun to design, manufacture and sell more upstream stem cell equipment through industrial acquisitions, mergers and acquisitions, etc., to separate and store stem cells, such as the automation of Boya Stem Cells. The stem cell separation equipment AXP®, the fully automatic cryogenic storage system BioArchive®, the fully automatic cryogenic biological sample storage system BSN-600 under the original energy biology, the biological sample cryogenic automatic storage system Hatch® under the base point biology. There are also some further downstream dedicated medical devices for stem cell therapy, such as PXP®, the instant bone marrow stem cell isolation system used in the operating room.

Summary

At present, stem cell therapy is constantly being standardized, and its research results are moving towards a bright future. Although numerous difficulties still need to be overcome, its safety and effectiveness still need to be comprehensively evaluated. However, as more domestic With the emergence of foreign stem cell pharmaceutical companies, I believe that stem cell therapy can shine in the future and benefit more patients!

Source: Science and Technology Innovation Express, China Securities, Xinsijie.com