[Shenzhen Business Daily] Small cells VS big industries

Article source: Shenzhen Business Daily Reading Chuang APP

Author: Shenzhen Commercial Daily chief reporter Wang Hairong

 

40-60 trillion, this is the number of cells in the human body. As the basic unit that constitutes the structure of human tissue and completes various physiological functions, stem cells, which have multi-differentiation potential and self-replication capabilities, are the focus of research in the field of life sciences today, and various innovative technologies are emerging one after another. Relying on the domestic ultra-large-scale market, stem cell storage and stem cell therapy have also become important directions for Shenzhen to cultivate new consumption in the field of life and health.

01
“Looking for the forefront of stem cell technology in Shenzhen, China”
Shenzhen Beike Biotechnology Co., Ltd., established sixteen years ago, is an innovative company dedicated to basic stem cell research and clinical translational research, and promoting stem cell therapy from laboratory to clinic.

In the first five years since its founding, Beike Biotech has collaborated with different medical institutions to quickly transform research results into new methods of clinical medical services through independent innovation of stem cell technology and decentralized model innovation of personalized cell therapy technology. At the same time, it has timely fed back clinical medical practice information to basic researchers, creating the prototype of China’s cell therapy industry transformation.

“The frontier of stem cell technology is not in Cambridge, Stanford, or Singapore, but in Shenzhen, China.” The world-famous economic magazine Business Week once reported. On March 9, 2008, the British Times’ article “Ten Chinese Companies Challenging the West” specifically mentioned Beike Biotech’s stem cell technology and its application after Huawei.

Company founder Hu Junyuan said that biotechnology is one of the most potential and dynamic technologies today. Life sciences and biotechnology with stem cells and gene sequencing as the core have made major breakthroughs in recent years. Among them, stem cells called “universal cells” can be induced to differentiate into more than 220 functional cells that make up the human body such as nerve cells, liver cells, and cardiomyocytes under certain conditions. They can achieve the effect of treating diseases by repairing damaged tissues and organs.

“Precise and personalized cell therapy will play an important role in future clinical medicine. New cell therapy technologies focusing on stem cells and immune cell therapy will provide more options for the treatment of refractory diseases,” Hu Junyuan said.

 

02
Accelerate the construction of “Cell Therapy Highway Network”
In September 2015, the Shenzhen Comprehensive Cell Bank and the Shenzhen (Beike) Regional Cell Preparation Center, which were specifically responsible for the construction of Beike, were officially established. This is also an important support and innovation carrier for Shenzhen to develop the “innovation chain + industrial chain” of personalized cell therapy.

According to the concept, the industrial development model of “comprehensive cell bank + regional cell preparation center + cell quality testing platform” is based on the comprehensive cell bank and regional cell preparation center that comply with the “Biosafety Law of the People’s Republic of China”, and uses “Internet +” as a means to lay a “cell therapy highway network” that can not only meet the timeliness of clinical needs, but also take into account the production scale of clinical demanders and advanced technology suppliers. It will promote the transformation of cell therapy technology-related industries from the “in-hospital preparation” model to a standardized cell storage and preparation model in line with international standards and development trends.

After six years of laying out the network, the “cell therapy highway network” built by Beike Biotech based on “one library, one center and one platform” has begun to take shape. It is distributed in South China, East China, Central China, North China, Southwest and Northwest China, and has built an innovative public technology platform and infrastructure for the clinical transformation of cell therapy technology.

 

03
“Grow” cells like rice
On January 13, in the cell preparation center on the 19th floor of Beike Building, Yuehai Street, Nanshan District, Shenzhen, technicians wearing clean protective clothing were preparing cells. Taking mesenchymal stem cells as an example, technicians use specific methods to isolate and extract mesenchymal stem cells from human tissues such as adipose tissue, umbilical cord, deciduous tooth tissue, placental decidua, etc., simulating a sterile environment with nutritional conditions such as temperature, pH, and osmotic pressure that are similar to the in vivo environment, and conduct in vitro culture and expansion so that the cells can survive, grow, reproduce, and maintain their main structure and function. After passing the test and identification, they are then long-term frozen and stored in a liquid nitrogen tank at minus 196°C.

Technicians told reporters that the culture period of mesenchymal stem cells ranges from about 2 to 3 weeks. Taking umbilical cord mesenchymal stem cells as an example, each technician can process more than a dozen samples a day, and will perform different operations on different cell samples according to the progress. “Cells need to undergo operations such as medium replacement and passage before cryopreservation. The cultivation process is like growing rice. We need to sow seeds first, then water, fertilize, loosen the soil, and finally harvest.” According to reports, a culture bottle has an area of ​​about 175 square centimeters, and the number of cells cultured in it can reach more than 10 million.

In clinical studies on endocrine system diseases, a patient weighing 50 kilograms required an infusion of 50 million cells in a single treatment. This dose is an effective dose based on preclinical research and clinical exploration. After the mesenchymal stem cells cultured in vitro are imported into the human body, they play a role in tissue repair and immune regulation. The infused cells grow and expand in the body, but are also recognized by the body’s immune system and eventually metabolized.

 

04
Standardization protects the industry  
The report “Global Cell Therapy Market 2017-2021” released by the internationally renowned consulting company Technavio pointed out that between 2017 and 2021, the global cell therapy market is expected to grow at a compound annual growth rate of 23.27%. With the growing demand for cell resource preservation and research and development, establishing various human cell resources, cell information preservation and service platforms with third-party certification or recognition, developing key common technologies such as cell cryopreservation and recovery, quality control, promoting the formulation of technical standards for cell resources, cell data collection and storage, and forming a traceability, standardization and information management system are important prerequisites and guarantees for promoting the development of cell therapy technology.

In order for the cells to have a legally valid “ID card”, Beike relies on a third-party cell quality testing agency to identify the safety and effectiveness of the cells, providing reliable guarantee for the clinical application of the cells.

In recent years, Beike Biotech has taken the lead in drafting and compiling Shenzhen local standards “SZDB/Z188-2016 Specifications for the Construction and Management of Cell Preparation Centers” and “SZDB/Z266-2017 Specifications for the Setup and Management of Comprehensive Cell Banks”, and participated in the formulation of the “Self-Discipline Standards for Quality Management of Stem Cell Preparation Preparations”, “Self-Discipline Standards for Quality Management of Immune Cell Preparation Preparations”, and the group standard “SZTT/SSCT” 002-2018 Specifications for Preparations of Human Umbilical Cord-Derived Mesenchymal Stem Cells for Clinical Research”, and the corporate standard “Q/BKSW 001-2018 Umbilical Cord-Derived Mesenchymal Stem Cells for Scientific Research” was formulated. In 2020, Beike Biotech took the lead in drafting and compiling Hebei provincial local standards “Cell Preparation Center Construction and Management Specifications” and “Comprehensive Cell Bank Construction and Management Specifications”, and led the drafting of Shenzhen local standards “Human Source Living Sample Transport Technology and Management Standards” and “Human Source Cell Products Transport Technology and Management Standards”.
As of November 2020, Beike Biotechnology has applied for 108 patents related to the field of cell technology, 56 of which have been authorized, and standardization construction continues to develop in depth.

05
 
Currently, molecular biology, represented by genetic science, is in its booming period. As a high-tech company that started with technology, Beike Biotech continues to make efforts in basic cell research, clinical research, and scientific and technological research, and its technology applications are developing in depth.

At the 2019 National Science and Technology Awards Conference held on January 10, 2020, the “Research on Key Technology Innovation and Clinical Application of Allogeneic Mesenchymal Stem Cells in the Treatment of Refractory Lupus Erythematosus” project jointly completed by the Department of Rheumatology and Immunology of Drum Tower Hospital Affiliated to Nanjing University School of Medicine, Beike Biotech, Jiangsu University, etc. won the second prize of the National Technology Invention Award. The research team applied allogeneic mesenchymal stem cells to treat refractory systemic lupus erythematosus for the first time, opening up a new treatment approach for other refractory autoimmune diseases.

Faced with the sudden COVID-19 epidemic, Beike Biotech also quickly responded to the national call and actively participated in technological research. In cooperation with Shenzhen Third People’s Hospital, we applied for the “Clinical Research on Human Umbilical Cord Mesenchymal Stem Cells for the Treatment of Severe Pneumonia Caused by Coronavirus” project and received approval from the Guangdong Provincial Department of Science and Technology for the “Guangdong Provincial Emergency Technology Research and Development Project for the Prevention and Control of Novel Coronavirus Infection”. The “Drug Research and Development of Mesenchymal Stem Cells for the Treatment of New Coronavirus Pneumonia” applied by Beike Biotech was approved by the National Ministry of Science and Technology as a key special project of “Science and Technology Assists the Economy 2020”.

At the same time, clinical research on mesenchymal stem cells for the treatment of critically ill patients with COVID-19, jointly conducted by Beike Biotech and a number of medical institutions in Yunnan, has also achieved preliminary results.

At present, Beike Biotechnology has cooperated with the Children’s Medical Center of Shiyan Taihe Hospital, Peking University Shenzhen Hospital, and Nanjing Drum Tower Hospital to conduct “clinical research on the safety and effectiveness of human umbilical cord-derived mesenchymal stem cells combined with modern rehabilitation in the treatment of cerebral palsy in children”, “clinical research on human umbilical cord mesenchymal stem cells in the treatment of type 2 diabetes” and “randomized blind parallel controlled multi-center clinical research on umbilical cord mesenchymal stem cells in the treatment of lupus nephritis” to promote the application of mesenchymal stem cell treatment technology.

As of December 2020, the number of stem cell clinical research registration institutions in my country has increased to 123, with 100 registered projects. Among them, five medical institutions, including the Second Affiliated Hospital of Kunming Medical University, Shiyan Taihe Hospital, Peking University Shenzhen Hospital, Shenzhen People’s Hospital, and the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, have joined forces with Beike Biotech to successfully pass the registration of stem cell clinical research institutions with the Health Commission, and 10 clinical research projects have been registered with the Health Commission.

It is worth noting that Shenzhen, which is building a pioneer demonstration zone for socialism with Chinese characteristics, has also introduced a series of supportive policies to promote stem cell therapy research.

The “Guiding Opinions of Shenzhen City on Promoting the Agglomeration Development of the Biomedical Industry” and supporting documents issued in January last year proposed the development of biotherapeutic technologies such as stem cell therapy, immunotherapy, and gene therapy. Actively promote the transformation of results and support the establishment of a somatic cell therapy clinical research and translation application platform.

On December 4, the Standing Committee of the Shenzhen Municipal People’s Congress held a working meeting on the drafting of the “Shenzhen Special Economic Zone Cell and Gene Industry Promotion Regulations” (tentative name) to listen to opinions from relevant departments and experts. This also indicates that Shenzhen will take the lead in legislating cell and gene therapy management.

Driven by a series of favorable policies, Shenzhen’s cell industry is expected to open up a new development space.

[Extended reading]
A notice

In June last year, Peking University Shenzhen Hospital released a notice recruiting subjects to conduct a clinical study of human umbilical cord mesenchymal stem cells in the treatment of type 2 diabetes.

The project “A Randomized, Parallel, Controlled Safety and Effectiveness Clinical Study of Human Umbilical Cord Mesenchymal Stem Cells in the Treatment of Type 2 Diabetes Under Different Transplantation Routes” jointly carried out by the hospital and Shenzhen Beike Biotechnology Co., Ltd. has passed the national stem cell clinical research filing. Its main purpose is to evaluate the feasibility, safety and effectiveness of human umbilical cord mesenchymal stem cells intravenous systemic infusion, local dorsal pancreatic artery infusion or combined infusion in the treatment of type 2 diabetes patients. This project has obtained medical ethics review approval for implementation.

The recruitment notice listed detailed conditions, including confirmed type 2 diabetes, 7% ≤ HbA1c ≤ 9.5% during the initial screening period, stable to 7% ≤ HbA1c ≤ 9.5% during the screening period, age between 18 and 70 years old, total insulin consumption before grouping ≤ 100IU/d, basal C-peptide ≥ 0.3 ng/ml, etc.

There are 21 notes listed on the back of the recruitment notice, including glutamic acid decarboxylase antibody (GADA) positivity, thiazolidinedione (TZDs) treatment within three months, severe drug allergy history or allergic constitution, etc. As long as one of them is touched, you will not be able to participate in the experiment.

“Meeting these requirements means that patients are not ideally treated with traditional methods, but their body functions can still support them in new treatment attempts.” Zhang Fan, chief physician of the Department of Endocrinology at Peking University Shenzhen Hospital, has been engaged in the clinical treatment of endocrine and metabolic diseases for more than 35 years. When she came to Shenzhen in 1999, the medical foundation of the Special Administrative Region was still very weak. Compared with the mature medical systems of other domestic cities that have been accumulated for a century, there was a big gap.

“If Shenzhen wants to make a breakthrough in medical care, our team needs to achieve differentiated development and explore cutting-edge technological innovation.” So as soon as she came to Shenzhen, she established a diabetes health club to help patients systematically understand the disease. When paying attention to the development of transplantation technology at the forefront of diabetes treatment, she initially only came into contact with pancreas, combined pancreas-kidney transplantation, islet transplantation, and islet cell transplantation. 20 years ago, she came into contact with cell therapy technology. The rapid advancement of immune cell therapy technology in the world convinced her that cell therapy could play a big role in the treatment of endocrine diseases.

“Sugar Friend” hopes to end the “long-distance running”

In decades of work, Zhang Fan has come into contact with all kinds of diabetic patients, who are also called “sugar friends.” “Can this disease be cured?” This is the question most commonly asked by “sugar friends.”

“We need to help patients find suitable treatments, which is particularly important in the treatment of endocrine diseases.” In Zhang Fan’s view, any technology cannot be one-size-fits-all. To find the right factors, in the future we will find the right people, the right dose for treatment, and the right treatment method. What kind of people will achieve better results with what kind of method? This is the rational and scientific attitude towards emerging technologies.

Wang Xing (pseudonym) is a “science friend” with a 16-year history of illness. He takes medicine or insulin every day. “It is definitely inconvenient, and this disease requires strict dietary control. You cannot eat high sugar and high calorie people. It is best not to touch cigarettes and alcohol. It is more painful for me.”

Because he is old, Wang Xing is still prone to forget things and often misses taking oral medication. “I am also worried that taking medicine all year round will cause damage to liver and kidney function. I need to inject insulin myself, which will cause pain and may cause hypoglycemia.”

Fortunately, the treatment of diabetes has been included in medical insurance, and Wang Xing’s monthly treatment costs are about a few hundred yuan. “The burden is not heavy, and the unit still has some reimbursement.”

Wang Xing’s unit has a physical examination every year. His diabetes was discovered earlier. After drug control, he has not experienced any serious complications for more than ten years. But in the past two years, he found that during his oral administration of metformin, he lost weight particularly significantly. After injury, the wound does not heal easily. Nowadays, hands and feet are prone to cold. “The peripheral circulation caused by diabetes is not good, and there may be small blood vessel lesions.” Wang Xing is worried about these complications. What made him particularly anxious was that his wife was also diagnosed with diabetes two years ago. “I’m worried that she will follow my old path and take medicine for the rest of her life.”

The concerns of “diabetic friends” have added to Zhang Fan’s motivation to accelerate the application of innovative technologies to find ways to treat metabolic diseases such as diabetes.

 

Innovation can be faster

Data shows that diabetes has become the third largest category of chronic non-communicable diseases after cardiovascular disease and cancer. There are about 110 million diabetic patients in my country, and the number of patients is increasing year by year. The systemic microvascular and macrovascular complications caused by diabetes threaten the lives and health of patients. At present, diabetes lacks effective treatment methods, and urgently needs innovative technologies and research clinical development.

“The recruitment plan is now progressing smoothly.” Zhang Fan explained that to obtain the experimental results, it will be as early as the end of 2022. “There will be found from the experimental numbers for the population, indications, and applicable treatment methods to which this method is applicable, and papers and new technologies will be formed as the basis for application for drugs. If approved, it can be used for clinical treatment in the future.”

In the process of building a pilot demonstration zone for socialism with Chinese characteristics, Shenzhen supports the innovative development of the biopharmaceutical industry, and Shenzhen People’s Congress takes the lead in launching legislation for the cell therapy industry. These news made Zhang Fan full of expectations. “If Shenzhen wants to build a special zone for stem cell therapy, I hope to walk on two legs, carry out scientific research on the one hand, and expand the clinical transformation of indications on the other hand, and Shenzhen’s innovation pace can be faster.”