Zhong Chao Han

Dr. Zhong Chao Han graduated from Jiangxi Medical College in 1982 and obtained a master’s degree from Fujian Medical University in 1984 in China. In 1988, Dr. Han got his PhD from the Faculty of Medicine, University of Occidental Bretagne in France. He worked in the Institute of Vascular and Blood and University Paris VII from 1989 to1997 and the University of Lorraine, France, as an excellence visiting Professor from 2017 to 2021. He was elected corresponding member of the French National Academy of Medicine in 2004, and a full member of the French National Academy of Technologies in 2014.

From 1998 to 2007, Dr. Han was the president of the Blood Diseases Hospital (Institute of Hematology) of the Chinese Academy of Medical Sciences and Peking Union Medical College, distinguished Professor of the Changjiang Scholars Award Program of the Ministry of Education, National Outstanding Youth Fund recipient. Since 2007, he has become the Director of the National Stem Cell Engineering Technology Research Centre, Director of the National Engineering Research Centre for Cell Products, President and Chief Scientist of Beijing Health and Biotech (H&B) Group.

Dr. Han has been engaged in stem cell research for more than 30 years. He devoted his career to translating stem cell knowledge gained from

laboratories to stem cell products and industrialization. He is the first system builder of the Tianjin model of stem cell translation, which represents a microcosm of stem cell research in China and offers rich experience for the development of translational medicine (STEM CELLS Transl Med. 2021;10:S4-S9). Han’s team was the first to treat effectively several lower limb ischemia by transplantation of patient’s own peripheral blood stem cells (Thromb Haemost,2004, 2007; Diabetes Care 2005), and to develop a P-MSCs bank for clinical uses in 2005 (Patent N.20051001542.2; Bull Acad Natl Med, 193:545,2009). Han and his colleagues demonstrated that P-MSCs are novel type of MSCs with hematopoiesis-supportive function and other potentials (Haematologica, 91:1017-26, 2006; Clinical Transplant, 2011).

Specially, Dr. Han’s team was the first to treat successfully the refractory systemic sclerosis (Cell Research, 2008:s71), multiple sclerosis (Mult Scler,15:644-6, 2009) using umbilical cord MSCs, and type 2 diabetes using placental MSCs (Front Med, 5:94-100, 2011). Dr. Han identified from placenta a population of CD106-positive MSCs with increased proangiogenic activity and immunoregulatory function (Plos One, 2011). Moreover, Han’s team developed for the first time a product of placental MSCs mixed with a biomaterial, which were prefabricated in syringe and frozen at -20℃ before use. Besides, Han’s team developed a series of standard platforms for cell products manufacturing and quality control.

Based on these platforms, several stem cell products have obtained IND and are under clinical investigation (see STEM CELLS Transl Med. 2021;10:S18-S30). The dosage form of these cell drugs includes intravenous injection, local injection, external hydrogel and Eye drops.

As the principal founder, Dr. Han has established several biotech companies specialized in different cell therapy and regenerative medicine. These companies are actually at the leading position of China and their business covers almost whole China. In addition, Han’s team has set up an international Cell Valley, a special science park combining the R&D center including several University Joint Lab, cell bank, CDMO platforms, regenerative medical center and industry cluster. To date, more than 200 000 units of perinatal MSCs have been stored and several thousands of patients with different refractory diseases were administrated to clinical application combing routine modern medicine and cell therapies (reported as a plenary lecture at the Meeting of French Academy of Technologies on June 9, 2021). The Cell Valley is exploring the full ability and trying to offer new hope to millions of patients with life-threatening diseases.

Dr. Han and his team have published more than 300 papers in English and 16 books on stem cells (cited > 13800 times) and obtained more than 30 local and national science and technology progress awards. Han’s vision and efforts to transform the results of good scientific research to

technological products and social benefits produced excellent results both in clinical application and in industrialization. Therefore, Dr. Han has been considered as the pioneer of stem cell industry of China.

Abstract – Stem cells based technologies

Thousands of clinical trials of stem cells have been registered in the past 20 years for a large panel of indications across the globe, which makes stem cell therapy one of the most intensely pursued and promising biotherapeutics. Analysis of clinical trials with first-generation mesenchymal stromal/stem cells (MSC) products has demonstrated safety, although clinical protocol still needs to be improved. A considerable amount of MSCs products have been completed the studies of chemistry manufacturing and control (CMC), and pre-clinical studies, and more than ten MSC products have been approved by the Medical Products Administration of several countries. Studies on other somatic stem cells as well as ESCs and iPSCs and ending on representatives with less potency—multi-, oligo- or unipotent cells have also made rapid progress for the use in regenerative medicine applications of injured or diseased tissues. Despite enthusiasm for stem cell therapy, the clinical and translational research of stem cells overall has been a slow and cumbersome process. In view of the diversity of types, sources and uses of stem cells, stem cell therapy could be a personalized replacement transplantation or a cells-as-drugs therapeutic approach. Therefore, the clinical translation and cell industry of stem cell technologies need to be explored by innovative ways.
Consistent with global development trends, recent years have witnessed the emphasis of translational research and the cell therapy industry in China. China’s regulatory strategies for cell therapy are generally similar to but slower than those of other developed countries. Parallel to the “cells-as-drugs” approach for cell therapy, the National Medical Products Administration (NMPA) and the National Health Commission (NHC) of China issued regulations on stem cell clinical research in 2015 as an alternative and flexible approach. This allows investigators from the designated stem cell clinical research institutes to apply for stem cell clinical research. Once investigators gather sufficient scientific evidence and clinical benefits from these clinical studies, they can use these data to apply for clinical trials through the “cells-as-drugs” approach. Based on such regulations, we have first established a translational technological system of stem cells, called Tianjin model (Chen H. Stem cell translational medicine: The Tianjin model revisited. Stem Cells Transl Med. 2021;10:S4–S9). To accelerate the clinical application and industrial development of stem cell technologies using Tianjin model, we have subsequently built a Cell Valley, a special park with R&D center, CDMO platforms, medical center, clinical grade cell bank, and industry clusters. The Cell Valley builds a bridge between basic research, clinical research and industrial development and explores its full ability to offer new hope to the patients with life-threatening diseases. The central vision of Cell Valley is to promote the stem cell industry by uniting the forces of many parties in the stem cell field. To date, the Cell Valley has produced some good social and economic benefits. Where we store precious stem cells in cell bank, prepare stem cells products in GMP factory for pre-clinical research in GLP facility, and perform clinical translational researches in hospital. Some breakthrough progress has been made in the development of perinatal MSC products, including injection products and an external applicator of perinatal MSCs mixed with hydrogel. Five products of stem cells have been approved to enter clinical trials by NMPA of China, and one approved by ANSM (French National Agency of Medicinal and Health Products Security). The clinical indications of these stem cell products include the diabetic foot ulcer, graft versus host disease (GvHD), chronic (plus acute) liver failure, critical lower limb ischemia, and acute respiratory distress syndrome (ARDS). These cell products are expected to complete clinical trials within 3-5 years. Here, we report briefly some clinical research outcome related to our stem cell products.
In summary, we have implemented a variety of initiatives to invent and develop the technological system, and have gathered momentum for its growth and consolidation. Our platforms met with a mass of interactions with an array of scientific, social, economic, and political variables and our experience may serve as a valuable and instructive reference for other institutions in stem cell translational medicine.