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Regenerative medicine in China: demands, capacity, and regulation
Burns & Trauma volume 4, Article number: 24 (2016)
Regenerative medicine (RM) is an emerging interdisciplinary field of research. Its clinical application focuses on the repair, replacement, and regeneration of cells, tissues, and organs by approaches including cell reprogramming, stem cell transplantation, tissue engineering, activating factors, and clone treatment. RM has become a hot point of research in China and other countries. China’s main and local governments have attached great importance to RM and given strong support in relevant policies and funding. About 3.5 billion RMB has been invested in this field. Since 1999, China has established about 30 RM centers and cooperates with many advanced countries in RM research and benefits from their cooperation. However, China needs to develop standards, regulations, and management practices suitable for the healthy development of RM. In this review, we focus on its great demand, capacity, and relative regulations.
Annually, about 100 million Chinese patients will receive treatment by tissue repair and regeneration technologies because of the sharp increase in various injuries, accidents, and diseases of aging. However, the current paradigm of “healing by scar tissue replacement,” regardless of superficial tissues or visceral organs, is stagnating and is far away from the ultimate goal of “regenerating the impaired organ.” Regenerative medicine (RM) is gradually being used to restore the intrinsic repair ability with stem cell transplantation, tissue engineering, activating factors, cell reprogramming, and genetic treatments. RM holds sound promise of restoring organ function that is impaired because of congenital disorders, acquired disease, trauma, and aging by replacing or regenerating cells, tissues, and even organs. RM is expected to transcend traditional organ transplantation and replacement. Stem cell technology and tissue engineering have an outstanding role in RM. RM will become one of the most promising areas of life science in the twenty-first century [1, 2].
In the past 20 years, the RM market has continued to grow in China and other countries such as the USA, Europe, Japan, and Singapore. As the largest developing country, China has impressed the world with its findings in stem cells, tissue engineering, active molecules, and gene therapy as well as its national strategies and regulation of RM. These achievements may benefit China in both disease treatment and society development .
Strategies, guidance, funding, and industrialization of RM in china
The central government of China supports the development of RM. In the 2006 National Plan for Long- and Medium-Term Scientific and Technological Development (2006–2020), stem cells and RM technologies were the important fields among the five biotechnologies (http://www.gov.cn/gzdt/2009-08/21/content_1398305.htm). Also, local governments have adopted stem cell research as one of the priorities of technological development and provided active support. Relevant government departments and academia have paid close attention to and encouraged the development of RM. In the Science & Technology on Public Health in China: A Roadmap to 2050, issued by the Chinese Academy of Sciences (CAS) , and the Study on the Long- and Medium-Term Development Strategy for China Engineering Science and Technology, issued by the Chinese Academy of Engineering (CAE) (http://news.sciencenet.cn/htmlnews/2012/12/273300-3.shtm), RM was considered a major research field. In the Roadmap of Translational Medicine in China issued by CAE, RM and biotherapy are main fields. Industrialization of RM is a part of the “12th Five-Year Planning” and will be nurtured as a source of economic growth.
The strategic science and technology projects from CAS can be divided into “Forward-Looking Strategic Priority Research Program of Science and Technology” and “Construction of Research Centers for Basic and Forefront Scientific Research.” Academia held three Xiangshan Science Conferences on RM, in 2005, 2010, and 2015, to discuss the philosophy, scope, and major breakthroughs needed for the development of RM in China and the key scientific issues to be addressed. In addition, the Xiangshan Science Conference organized seminars on stem cell biology and cloning, strategies for research and development of gene therapy and biomaterials, and tissue engineering.
Regulatory and scientific guidance
Policies and regulations reflect that China is gradually strengthening the management of RM research and clinical application. Since 1999, when the Ministry of Health (MH) promulgated the first Umbilical cord blood stem cell bank management approach (Trial), about 30 rules and regulations have been issued by the Ministry of Science and Technology (MST), the MH, and the State Food and Drug Agency (SFDA) (Table 1).
In 2011, the First National Stem Cell Research Guidance and Coordination Committee was established for the overall design and scientific planning of stem cell research in China. In December 2011, the Notice on Carrying out Self-inspection and Self-rectification Campaign Regarding Stem Cell Clinical Research and Application was issued. In 2013, the stem cell clinical research and application rectification lead group of the MH and SFDA formulated the regulations Management Specification of Stem Cell Clinical Trials (Trial), Management Specification of Stem Cell Clinical Trial Research Base (Trial), and Stem Cell Preparation Quality Control and Pre-clinical Research Guidelines (Trial). These regulations will be implemented soon and help in the development of RM in China. In 2015, China MH opens the window to allow the stem cell clinic trial and stem cell research bases which will promote the development of stem cell research and translational application in China.
Funding support and resources
Multiple sources are funding RM studies and translational application. After 1999, the MST approved the National Program on Key Basic Research Project (973 Program) related to tissue engineering, and the stem cell field had the largest number of “973 Program” projects. Research into the clinical transformation and application of stem cell therapy was established in the biotechnology and medical technology field of the “863 Program.” The National Natural Science Foundation (NNSF) funded about 200 million RMB for this study, including 5627 items (Fig. 1a, b). Up to now, about 3 billion RMB from the MST, CAS, and NNSF has been invested in this field. Both the amount of funding and number of projects are increasing annually. Other funding for RM from companies is about 500 million RMB. In 2015, NNSF plans to invest RM research as its “Great Research Plan,” and MST has issued its new scientific research grand with about 21 billion RMB in RM field.
Translating outcomes into industrialization
The establishment of centers and technological translational application are important for RM development. Since 1999, China has established about 30 RM centers. These centers are involved in stem cell research and its translational application (e.g., national stem cell east center and national stem cell centers in Tianjin, Qingdao, Wuxi, Taizhou, etc.) (http://www.bioon.com/biology/cell/28500.shtml); national stem cell and RM technology innovation strategic alliance (sponsors and governing members include 27 first-class research institutes, well-known three-A hospitals, several “211 Project” key universities and industry leaders); and a tissue engineering innovation center in Shanghai. In 2011, the first academic workstation for the industrialization of stem cell technology was launched in the Inner Mongolia Autonomous Region. Companies such as Cyagen Biosciences (Guangzhou) and Hangzhou Biowish Technology (Biowish) are specialized in the development and sales of stem cell products. In 2009, NeoStem announced that it had reached an exclusive agreement for strengthening biomedical cooperation with Shanghai enterprises. This agreement aims to establish a network of stem cell collection and treatment centers in Shanghai, Jiangsu, Zhejiang, Fujian, Anhui, and Jiangxi provinces. In 2010, the Beike Stem Cell Bank and Stem Cell Preparation Laboratory successfully passed the ISO 9001 quality management system certification and obtained the qualification certification issued by China Quality Certification Center, becoming the first comprehensive stem cell bank to pass ISO 9001 quality management system certification in China (http://www.bioon.com/industry/enterprisenews/432100.shtml).
Production in academic fields
Publication of valued scientific papers is one of the very important indicators to evaluate investment and production in academic fields. The total number of scientific papers dealing with RM has increased quickly in China, as has the number published in leading scientific journals in China and internationally (Fig. 2). Since the 1960s, the USA has published 599 articles about stem cells in Cell and its subjournals (36), Germany published 45, Japan 36, and China only 17. Since 2000, the number of annual patent applications for stem cells has increased quickly and amounted to 1333 in 2009. In 2011, the Chinese literature related to stem cells outnumbered that of published by German, Japanese, and UK researchers and ranked second. In 2012, it had increased. In terms of citations, the USA ranked the first, with a mean of 32.2 citations per item. However, citations for Chinese publications are increasing annually, and the mean number is currently 10.19. For patent applications, as of March 2010, the number of China stem cell-related patent applications and patent applications as a patent priority country was ranked the sixth and third in the world, respectively. The USA, Japan, and China have applied for more patents as patent priority countries (http://www.chinainfo.gov.cn/Report/ArticlesView.aspx?aid=7924).
International collaboration and opportunities for RM in China
Open and cooperative regulations are basic in China. Since 2005, China has cooperated with many countries that are advanced in RM at different levels. Six world-renowned comprehensive RM research institutions from Germany, the USA, Canada, Spain, and The Netherlands established a Regenerative Medicine Coalition (RMC) to jointly promote the research and innovation of RM therapy at cellular levels (Table 5). Even some large foreign pharmaceutical companies, such as General Electric and Sanofi-Aventis, have invested in China for stem cell-related research and achieved relevant results (http://lib.cet.com.cn/paper/szb_con.aspx?id=140472) [47, 48]. Also, the use of theories and skills of RM in military medicine is one of the important fields in the future .
Great demands in RM are not only in China but also in the world. Their theories and key skills or products are used not only in peacetime but also in military field . The Chinese government attaches great importance to this field, and vigorous investments from the government and companies may accelerate the progress in basic research and translational application. Innovation and international cooperation will be emphasized in future studies. Other sound administrative system, laws, technical specifications, and guidelines are very important in pushing their healthy and orderly development.
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This study was supported in part by the National Nature Science Foundation of China (81121004, 81230041, 81171812, 81272105, and 81171798) and the National Basic Science and Development Programme (973 Program, 2012CB518105) and National Science and Technology Major Project (2011ZXJ07104B-03B).
BC and XF conceived and designed the project, collected and analyzed the data, and participated in the writing process. SL participated in data collection. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
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Cheng, B., Lu, S. & Fu, X. Regenerative medicine in China: demands, capacity, and regulation. Burn Trauma 4, 24 (2016). https://doi.org/10.1186/s41038-016-0046-8
- Regenerative medicine
- Stem cell
- Tissue engineering