Open Access

Regenerative medicine in China: demands, capacity, and regulation

Burns & Trauma20164:24

https://doi.org/10.1186/s41038-016-0046-8

Received: 23 March 2016

Accepted: 27 April 2016

Published: 2 June 2016

Abstract

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.

Keywords

Regenerative medicine Stem cell Tissue engineering China

Background

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 [3].

Review

Strategies, guidance, funding, and industrialization of RM in china

National strategies

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) [4], 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).
Table 1

Management specification of stem cell transplantation techniques

Time

Management specification of stem cell transplantation techniques

2006

Unrelated Hematopoietic Stem Cell Transplantation Technique

 

Unrelated Hematopoietic Stem Cell Transplantation Collection Technique

2009

Cord Blood Stem Cell Therapy Technology (Trial)

 

Tissue-engineering Tissue Transplantation Therapy Technique (Trial)

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.
Fig. 1

National Natural Science Foundation of China investment in regenerative medicine from 2000 to 2014. a Amount of funding. b Number of funds

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).
Fig. 2

Outputs of regenerative medicine research papers compared with major countries (ISI Web of Knowledge). a Stem cells. b Tissue engineering

Also, many monographs on stem cells or tissue engineering and RM have been published which play some role in pushing the research of RM in China (Tables 2, 3, and 4).
Table 2

Main monographs on regenerative medicine published in China

Time

Name

Author

Publishing company

2008.03

Regenerative Medicine: From Basic to Clinic Research

Fu Xiaobing, Wang Zhengguo, Wu Zuze [5]

Shanghai Scientific and Technical Publishers

2010.05

Regenerative Medicine: Theory and Technology

Pei Xuetao [6]

Science Press

2012.03

Regenerative Medicine

Ding Fei, Liu Wei, Gu Xiaosong [7]

People’s Medical Publishing House

2013.08

Regenerative Medicine: Basic and Clinical Research

Fu Xiaobing, Wang Zhengguo, Wu Zuze [8]

People’s Medical Publishing House

2014.10

Tissue Engineering and Regenerative Medicine

Jin yan [9]

People’s Medical Publishing House

2015.03

Chinese Discipline Development Strategy Regenerative Medicine

Chinese Academy of Sciences [10]

Science Press

Table 3

Main monographs on stem cells published in China

Time

Name

Author

Publishing company

1988.01

Basic Hematopoietic Stem Cell Transplant

Wu Zuze [11]

People’s Medical Publishing House

2000.04

Stem Cells and Developmental Biology

Ye Xinsheng, Xu Tian, Tang Xifang, Pei Xuetao [12]

Military Medical Science Press

2000.09

Peripheral Blood Stem Cell Transplantation

Da Wanming, Pei Xuetao [13]

People’s Medical Publishing House

2000.11

Hematopoietic Stem Cells Theory and Transplant Technique

Han Zhongchao [14]

Henan Science and Technology Press

2003.07

Stem Cell Biology

Pei Xuetao [15]

Science Press

2005.03

Stem Cells Theory and Technique

Wang Tinghua, Li Liyan [16]

Science Press

2005.05

Stem Cells Biology

Hu Huozhen [17]

Sichuan University Press

2006.05

Principles, Technology and Clinic of Stem Cell

Zhao Chunhua [18]

Chemical Industry Press

2006.07

Neural Stem Cell Foundation and Application

Zhu Xiaofeng [19]

Science Press

2006.12

Neural Stem Cell

Xu Ruxiang [20]

Military Medical Science Press

2007.03

Hematopoietic Stem Cell Biology and Research Methods

Wang Yaping [21]

Science Press

2007.07

Stem Cell Aging and Disease

Wang Yaping [22]

Science Press

2008.02

Fundamental and Clinic Research of Stem Cells

Yu Yue [23]

Press of University of Science and Technology of China

2010.07

New Technologies of Stem cell Application

Yang Xiaofeng, Zhang Sufen, Guo Zikuan [24]

Military Medical Science Press

2010.01

Clinical Research of Mesenchymal Stem Cells

Wang Tong [25]

People’s Medical Publishing House Co., Ltd

2011.08

The Basis, Ethics and Principles of Clinical Applications of Stem Cells

Jin Kunlin [26]

Science Press

2011.12

Research Legal Regulation of Human Embryonic Stem Cell

Zhao Xu [27]

Shanghai People’s Publishing House

2012.04

Mesenchymal Stem Cells: Basic Research and Clinical Application

Han Zhongchao [28]

Science Press

2012.10

Clinical Research and Application of Stem Cells

Gu Yongquan, Han Zhongcao, Fu Xiaobing [29]

People’s Medical Publishing House

2012.10

Application of Stem Cell Technology for Cardiovascular Diseases

Ma Yitong, Ge Junbo [30]

People’s Medical Publishing House

2012.06

Development Report on Technology and Industry of Stem Cell

Dai Tao, Chi Hui, Fu Xiaobing, Pei Xuetao, Zhou Qi, Li Defu, Lan Baoshi [31]

Science Press

2014.06

Practice of Hematopoietic Stem Cell Transplantation

Huang Xiaojun [32]

People’s Medical Publishing House

2014.07

Clinical Progress of Stem Cell Therapy

Han Zhongchao [33]

Tianjin Science and Technology Translation Publishing Co., Ltd

Table 4

Main monographs of tissue engineering published in China

Time

Name

Author

Publishing Company

2002.09

Tissue Engineering

Yang Zhiming [34]

Chemical Industry Press

2003.08

Repair of Medicine and Tissue Engineering

Lao Weide [35]

Chemical Industry Press

2004.06

Principles and Protocol of Tissue Engineering

Jin Yan [36]

Fourth Military Medical University Press

2004.12

The Theory and Practice of Tissue Engineering

Cao Yilin [37]

Shanghai Scientific and Technical Publishers

2005.06

Basic and Clinic Research on Tissue Engineering

Yang Zhiming [38]

Sichuan Scientific and Technological Press

2006.05

Tissue Engineering: A Laboratory Manual

Pei Guoxian, Wei Kuanhai, Jin Dan [39]

Military Medical Science Press

2008.01

Tissue Engineering

Cao Yilin [40]

Science Press

2009.05

Tissue Engineering of Skin

Wu Jinjin, ZhuYoutang [41]

Military Medical Science Press

2010.02

Biomaterials and Tissue Engineering

Xiong Dangsheng [42]

Science Press

2011.03

Stem Cell Tissue Engineering: Basic Theory and Clinical Application

Wang Dianliang [43]

Science Press

2012.01

Introduction to Human Tissue Engineering

Guan Guangju, Jiang Duyin [44]

Shandong University Press

2015.01

Fabrication and Structure Performance of Biodegradable Tissue Engineering Scaffolds

Cui Zhixiang [45]

National Defence Industry Press

2015.06

Medical Polysaccharide Material

Dan Huaping [46]

Science Press

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 [49].
Table 5

Collaborations between China and other countries in regenerative medicine research

Country of collaboration

Time

Objects

France

2005

Institute of Zoology (IOZ), Chinese Academy of Sciences, and the French National Institute for Agricultural Research

2007

The Chinese-French Joint Laboratory of Biology of Embryonic Cells of Mammals

Australia

2007

Sino-Australia Center of Excellence for Stem Cell Science

Canada

2007

Monash Immunology and Stem Cell Laboratories (MISCL) was awarded a federal government grant to establish a joint Australia-China Centre for Excellence in Stem Cell Science with Peking University.

2009

The Ministry of Science and Technology and the Canadian Institutes of Health Research signed a memorandum of understanding.

UK

2005

The Committee of the National Natural Science Foundation of China and the UK Medical Research Council signed a memorandum of cooperation.

2009

Scottish Centre for Regenerative Medicine (SCRM) and Peking University Stem Cell Research Center (PKUSCRC) established a national international joint research center.

2012

UK Medical Research Council and the National Natural Science Fund Committee cooperated to jointly fund a stem cell research project.

USA

2009

The California Institute for Regenerative Medicine (CIRM) and the Chinese Ministry of Science and Technology (MST) signed an agreement to collaborate on stem cell research.

Germany

2009

The National Natural Science Fund Committee and the German Science Foundation cooperated to jointly fund a stem cell research project.

Conclusions

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 [49]. 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.

Declarations

Acknowledgements

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).

Authors’ contributions

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.

Competing interests

The authors declare that they have no competing interests.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
College of Life Sciences, Medical College of PLA, General Hospital of PLA
(2)
The Key Laboratory of Trauma Treatment & Tissue Repair of Tropical Area, PLA
(3)
Ruijin Hospital, Shanghai Jiao Tong University
(4)
Chinese Academy of Engineering (Division of Medical and Health), College of Life Sciences, Medical College of PLA, General Hospital of PLA

References

  1. Nerem RM. Regenerative medicine: the emergence of an industry. J R Soc Interface. 2010;7(Suppl 6):S771–S775.Google Scholar
  2. Stoltz JF, Isla N, Li YP, Bensoussan D, Zhang L, Huselstein C, et al. Stem Cells and Regenerative Medicine: Myth or Reality of the 21th Century. Stem Cells Int. 2015;2015:734731.Google Scholar
  3. Fu X. Regenerative medicine research in China: from basic research to clinical practice. Science China Life Sciences. 2014;57(2):155-6.Google Scholar
  4. Chen K, Lin Q, Wu J. Science & Technology on Public Health in China: A Roadmap to 2050. Berlin, Heidelberg; Springer Berlin Heidelberg; 2010.Google Scholar
  5. Fu X, Wang Z, Wu Z. Regenerative medicine: from basic to clinic research. Shanghai: Shanghai Scientific & Technical Publishers; 2008.Google Scholar
  6. Pei X. Regenerative medicine: theory and technology. Beijing: Science Press; 2010.Google Scholar
  7. Ding F, Liu W, Gu X. Regenerative medicine. Beijing: People’s Medical Publishing House; 2012.Google Scholar
  8. Fu X, Wang Z, Wu Z. Regenerative medicine: basic and clinical research. Beijing: People’s Medical Publishing House; 2013.Google Scholar
  9. Jin Y. Tissue engineering and regenerative medicine. Beijing: People’s Medical Publishing House; 2014.Google Scholar
  10. Chinese Academy of Sciences. Chinese discipline development strategy regenerative medicine. Beijing: Science Press; 2015.Google Scholar
  11. Wu Z. Basic hematopoietic stem cell transplant. Beijing: People’s Medical Publishing House; 1988.Google Scholar
  12. Ye X, Xu T, Tang X, Pei X. Stem cells and developmental biology. Beijing: Military Medical Science Press; 2000.Google Scholar
  13. Da W, Pei X. Peripheral blood stem cell transplantation. Beijing: People’s Medical Publishing House; 2000.Google Scholar
  14. Han Z. Hematopoietic stem cells theory and transplant technique. Zhengzhou: Henan Science and Technology Press; 2000.Google Scholar
  15. Pei X. Stem cell biology. Beijing: Science Press; 2003.Google Scholar
  16. Wang T, Li L. Stem cells theory and technique. Beijing: Science Press; 2005.Google Scholar
  17. Hu H. Stem cells biology. Chengdu: Sichuan University Press; 2005.Google Scholar
  18. Zhao C. Principles, technology and clinic of stem cell. Beijing: Chemical Industry Press; 2006.Google Scholar
  19. Zhu X. Neural stem cell foundation and application. Beijing: Science Press; 2006.Google Scholar
  20. Xu R. Neural stem cell. Beijing: Military Medical Science Press; 2006.Google Scholar
  21. Wang Y. Hematopoietic stem cell biology and research methods. Beijing: Science Press; 2007.Google Scholar
  22. Wang Y. Stem cell aging and disease. Beijing: Science Press. 2007.Google Scholar
  23. Yu Y. Fundamental and clinic research of stem cells. Hefei: Press of University of Science and Technology of China; 2008.Google Scholar
  24. Yang X, Zhang S, Guo Z. New technologies of stem cell application. Beijing: Military Medical Science Press; 2010.Google Scholar
  25. Wang T. Clinical research of mesenchymal stem cells. Beijing: People’s Medical Publishing House Co.,Ltd; 2010.Google Scholar
  26. Jin K. The basis, ethics and principles of clinical applications of stem cells. Beijing: Science Press; 2011.Google Scholar
  27. Zhao X. Research legal regulation of human embryonic stem cell. Shanghai: Shanghai People's Publishing House; 2011.Google Scholar
  28. Han Z. Mesenchymal stem cells: basic research and clinical application. Beijing: Science Press; 2012.Google Scholar
  29. Gu Y, Han Z, Fu X. Clinical research and application of stem cells. Beijing: People’s Medical Publishing House; 2012.Google Scholar
  30. Ma Y, Ge J. Application of stem cell technology for cardiovascular diseases. Beijing: People’s Medical Publishing House; 2012.Google Scholar
  31. Dai T, Chi H, Fu X, Pei X, Zhou Q, Li D, Lan B. Development report on technology and industry of stem cell. Beijing: Science Press; 2012.Google Scholar
  32. Huang X. Practice of hematopoietic stem cell transplantation. Beijing: People’s Medical Publishing House; 2014.Google Scholar
  33. Han Z. Clinical progress of stem cell therapy. Tianjin: Tianjin Science and Technology Translation Publishing Co., Ltd; 2014.Google Scholar
  34. Yang Z. Tissue engineering. Beijing: Chemical Industry Press; 2002.Google Scholar
  35. Lao W. Repair of medicine and tissue engineering. Beijing: Chemical Industry Press; 2003.Google Scholar
  36. Jin Y. Principles and protocol of tissue engineering. Xi’an: Fourth Military Medical University Press; 2004.Google Scholar
  37. Cao Y. The theory and practice of tissue engineering. Shanghai: Shanghai Scientific & Technical Publishers; 2004.Google Scholar
  38. Yang Z. Basic and clinic research on tissue engineering. Chengdu: Sichuan Scientific and Technological Press; 2005.Google Scholar
  39. Pei G, Wei K, Jin D. Tissue engineering: a laboratory manual. Beijing: Military Medical Science Press; 2006.Google Scholar
  40. Cao Y. Tissue engineering. Beijing: Science Press; 2008.Google Scholar
  41. Wu J, Zhu Y. Tissue engineering of skin. Beijing: Military Medical Science Press; 2009.Google Scholar
  42. Xiong D. Biomaterials and tissue engineering. Beijing: Science Press; 2010.Google Scholar
  43. Wang D. Stem cell tissue engineering: basic theory and clinical application. Beijing: Science Press; 2011.Google Scholar
  44. Guan G, Jiang D. Introduction to human tissue engineering. Jinan: Shandong University Press; 2012.Google Scholar
  45. Cui Z. Fabrication and structure performance of biodegradable tissue engineering scaffolds. Beijing: National Defence Industry Press; 2015.Google Scholar
  46. Dan H. Medical polysaccharide material. Beijing: Science Press; 2015.Google Scholar
  47. Cao N, Liu Z, Chen Z, Wang J, Chen T, Zhao X, et al. Ascorbic acid enhances the cardiac differentiation of induced pluripotent stem cells through promoting the proliferation of cardiac progenitor cells. Cell Res. 2012;22(1):219–36.Google Scholar
  48. Fu X. Regenerative medicine research in China: from basic research to clinical practice. Science China Life Sciences. 2014; 57(2):155-6.Google Scholar
  49. Fu X. Military medicine in china: old topic, new concept. Mil Med Res. 2014;1:2–5. Google Scholar

Copyright

© The Author(s) 2016

Advertisement