Industry Frontiers

In the long journey of medical development, stem cell therapy is like a shining but mysterious new star, carrying the hope of countless patients' recovery, but also facing numerous challenges. After years of exploration and research, China finally welcomed the launch of its first stem cell therapy drug this year. Behind this milestone event is the hard work of countless researchers and policy makers, reflecting the arduous process of stem cell therapy from theory to clinical practice.

1、 Stem cells: the miraculous' seed 'of the human body

Stem cells, the miraculous "seeds" in the human body, possess pluripotency and are believed to have enormous potential for repairing and replacing damaged cells and tissues in the body. Starting from embryonic development, stem cells are like the architects of life, constantly differentiating and proliferating to construct the complex tissue and organ system of the human body. After the delivery of the fetus, the stem cells in the body continue to function until the age of 20, amplifying 60 trillion individual cells and shaping the appearance of an adult. They can not only replicate themselves, but also be influenced by their surrounding environment, improving organ function through paracrine secretion and large-scale implantation, just like fertilizing and improving the "soil" of the human body, eliminating aging cells at designated locations, and fighting against the aging process.

However, transforming stem cells from laboratory research subjects into clinically usable drugs is not an overnight process. Previously, there was controversy over the approval process for stem cell therapy technology (non blood related fields), and whether it should be approved as a drug or registered as a medical technology has always been a hot topic of discussion in the industry. Until January 2nd of this year, the National Medical Products Administration conditionally approved the launch of China's first stem cell therapy drug, Amimatosa Injection, through a priority review and approval process. It is used to treat acute graft-versus-host disease with hormone therapy failure mainly affecting the digestive tract of those over 14 years old. This means that China has preliminarily opened up key links in the path of stem cell drug commercialization, and the regulatory system has gradually been established and improved.

2、 Research dilemma: the path of exploration through thorns and thorns

Looking back on the past, the development of stem cell therapy has faced many challenges. Firstly, there are challenges at the level of scientific research. On the one hand, the "viability" of stem cells makes the traditional drug evaluation system almost "ineffective". Chemical drugs and macromolecular drugs have clinical doses and usage determined based on half-life, while the behavior of stem cells after entering the human body is elusive. They not only do not follow the attenuation rules of conventional drugs, but may even proliferate. The growth and decline dynamics within each individual are different, which poses unprecedented challenges for toxicological evaluation, safety evaluation, and pharmacological evaluation. For example, how to determine the appropriate cell dosage that can ensure therapeutic effect without causing excessive proliferation or other adverse reactions has become a difficult challenge that researchers must overcome.

On the other hand, the heterogeneity of stem cells makes the therapeutic effect highly variable. Stem cells obtained from different individual sources and preparation methods have differences in characteristics and functions. Even for the same disease, the same stem cell therapy may have significant therapeutic effects on some patients, but may have no effect on others. Taking mesenchymal stem cells as an example, although their immunogenicity is relatively low and the possibility of rejection is small, their vitality fluctuates greatly between different batches; Hematopoietic stem cells, embryonic stem cells, neural stem cells, and other cells have strong immunogenicity and require typing, breeding, or genetic modification before use, further increasing the complexity of treatment. In addition, the fate regulation and reprogramming technologies of stem cells in the body are still immature. In addition to the inherent risks of the cells themselves, even a slight mistake in the extraction, preparation, storage, and reinfusion processes may introduce infection risks and endanger the health of patients.

The insufficient explanation of the mechanism of action of stem cell therapy in basic research has seriously constrained its development. Unlike chemical drugs that can determine indications based on molecular groups, it is currently difficult to accurately predict the therapeutic effectiveness of stem cells for specific diseases based on their refined cellular characteristics. This has led to a certain degree of blindness in the research and development process, delaying the emergence of stem cell therapy drugs.

3、 Clinical trials: moving forward under rigorous testing

Entering the clinical trial phase, challenges arise one after another. Due to the particularity of stem cell therapy, safety verification is extremely complex. Medical institutions participating in clinical trials must have strict qualifications. As of early December 2023, only 141 stem cell institutions have been registered on the national medical research registration and filing platform, with a total of 127 stem cell research registration projects approved. Before any stem cell therapy drug is launched, it not only needs to have solid preclinical drug development research data support, but also needs to undergo a series of rigorous clinical trials on the safety and effectiveness of the drug in these formal medical institutions, work closely with drug regulatory authorities, and go through numerous tests before obtaining market approval.

In the past, the field of stem cell therapy was plagued by chaos driven by interests. Search for "stem cell therapy" on search engines and social media, and you can find many "stem cell therapy centers" with various names. They can recruit patients under the banner of treating diabetes, liver disease, brain atrophy, Parkinson's disease, autism and other difficult and miscellaneous diseases. The medical procedures are optional, and there is no need to register, but telephone consultation. This chaotic situation not only harms the interests of patients, but also disrupts industry order, posing a crisis of trust for truly scientific and rigorous stem cell research and clinical trials. It also prompts regulatory authorities to accelerate the pace of rectification and strengthen regulatory constraints.

4、 Policy Assistance: Clearing the Clouds and Seeing the Dawn of the Sun

To promote the development of stem cell therapy, China's policies continue to make efforts. In May 2024, the Beijing Food and Drug Administration issued China's first production license for stem cell drugs, marking a major policy breakthrough for the China National Medical Products Administration's Center for Drug Evaluation (CDE) in the field of stem cell drugs. At the same time, a series of guiding principles have been successively introduced, such as the "Technical Guidelines for Clinical Trials of Mesenchymal Stem Cell Prevention and Treatment of graft-versus-host Disease" issued by the Drug Evaluation Center on January 12, 2024, providing guidance for research and development and regulating industry development. Various regions are actively exploring innovative models. Hainan has issued the "Regulations on Promoting Biomedical New Technologies in the Boao Lecheng International Medical Tourism Pilot Zone of Hainan Free Trade Port", which will be implemented from February this year. It encourages clinical research and translational applications of biomedical new technologies such as cell therapy, gene therapy, and tissue engineering in the pilot zone, creating a favorable policy environment for stem cell therapy.

On the industrial side, the clinical application of stem cells also faces many practical challenges. The biggest challenge for cell drugs lies in accessibility, which involves key elements such as large-scale preparation, quality control, and shelf products. Large scale production is the core of reducing costs and improving accessibility. At present, the drug cost of Cell&Gene Therapy (CGT) is high, mainly covering five major areas: culture medium, equipment and consumables, labor and operation, quality control, and factory equipment. To achieve low-cost and stable production, it is necessary to independently develop automated, enclosed, and scalable equipment for producing cell drugs in the future, break through the bottleneck technology of the industry chain, and achieve domestic substitution of cell product raw materials and high-end reagents.

The quality control process requires extremely high standards. The quality control of stem cells is stricter than that of chemical drugs. The produced cells need to undergo comprehensive inspections such as functional testing, epigenetic testing, tumorigenicity testing, and various heat source testing to ensure the quality, safety, and stable efficacy of cell products. This undoubtedly increases the difficulty and cost of production.

The development of shelf style products is also urgent. Currently, most cell therapies rely on in vitro induction and expansion of autologous cells. This personalized therapy is influenced by the patient's health status, specimen collection, culture preparation, and other factors

Due to various factors such as limitations in therapeutic applications, it is difficult to become a standardized and high-quality treatment product. To this end, researchers are actively exploring methods such as stable acquisition of induced pluripotent stem cells (iPSCs) using feeder free, non integrated, and virus free reprogramming techniques to improve clinical safety; Introducing CRISPR/Cas9 gene editing to construct immune escape iPSCs and reduce the risk of transplant rejection; Improve cell purity and yield, transplant without sorting, and reduce production costs; Optimize filling and preservation techniques, develop low damage filling methods and new freezing liquids.

Despite the bumpy road ahead, the prospects for stem cell therapy remain bright. Researchers have never stopped exploring, as evidenced by the strategic cooperation between Director Wu Bo's team of General Surgery at Shanghai Sixth People's Hospital and Yuanwu Medicine. The two sides focused on iPSC technology, deeply cooperated in the fields of cell development and differentiation methods, in vitro function detection technology development, model animal development, cell drug research and development, quality standards, etc., committed to opening up a new Xintiandi of iPSC technology application for the treatment of metabolic system problems, and promoting stem cell drugs to clinical use. Yuanwu Medicine focuses on the development and application of iPSC technology, and its Parkinson's and osteoarthritis pipelines have entered the animal experimental stage, which is expected to bring new hope to patients with these chronic degenerative diseases.

Stem cell therapy, as an emerging medical approach, is at a critical stage of growth. The launch of the first stem cell therapy drug is a major breakthrough, but it is only the beginning. In the future, the government, research institutions, and enterprises need to work together to continuously overcome scientific challenges, improve regulatory oversight, optimize industrial processes, and truly benefit patients with stem cell therapy. This will open a new era of medical care and write a magnificent chapter for human health. In this journey, every experiment, policy, and product iteration carries the weight of life and the dawn of hope, inspiring people to forge ahead and strive towards the goal of overcoming more difficult diseases and improving the health and well-being of the whole nation. With the continuous advancement of technology, it is believed that stem cell therapy will gradually shed its mysterious veil and grow into a solid force safeguarding human health, leaving a profound mark in the history of medicine.

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Source: Xianji.com

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