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Institute of Biotherapy for Hematological Malignancies of Shandong University; Shandong University-Karolinska Institutet Collaborative Laboratory for Stem Cell Research
2024-04-09 09:51     (点击: )

Establishment and Development:

Shandong University-Karolinska Institutet Collaborative Laboratory for Stem Cell Research was born from a shared vision and passion for tumor immunotherapy, stem cells, and regenerative medicine study. Recognizing the need for in-depth cooperation with famous scholars of KI in the field of stem cells, our founders decided to establish a laboratory dedicated to stem cell research. The collaboration started in 2005 when prof. Chengyun Zheng was recruited from KI by Shandong University, and was a natural continuation of his 8 years’ research education and training at KI. The earlier collaborations were mainly in studies of cancer biology and immunology, as well as inherent hematological disorders, such as familial hemophagocytic lymphohistiocytosis (FHL). Institute of Biotherapy for Hematological Malignancies of Shandong University was established in 2010. Subsequently in 2014, under the promotion of prof. Zheng Chengyun, Shandong University-Karolinska Institutet Collaborative Laboratory for Stem Cell Research was established. With dramatic developments in stem cell research, especially in the fields of inducible pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs), the collaboration team has gradually shifted their research collaborations in stem cell therapies. Additionally, we have forged valuable collaborations and partnerships with prof. Qi Zhou (Academician of Chinese Academy of Sciences, State Key Laboratory of Stem Cell, Chinese Academy of Sciences) and Qing Yi (internationally famous multiple myeloma immunology expert, Director of Center for Hematologic Malignancy Research Institute, Houston Methodist) to further enhance our research capabilities in immunotherapy for hematological tumors.

 

Team Members:

Our team is composed of 2 leading experts in their fields, 13 young and passionate researchers, and 2 support staff dedicated to excellence.

Prof. Chengyun Zheng, PhD of Hematology in Karolinska Institute, Sweden, Director of the team, PhD supervisor of Shandong University, dedicated to immunotherapy and stem cell basic and clinical application research.

Prof. Dawei Xu, Director of Hematology Laboratory in Karolinska Institutet.

Prof. Yang Jiang, PhD of Immunology in Shandong University, Associate professor of Shandong University, dedicated to immunotherapy and stem cell research.

Prof. Dexiao Kong, PhD of Hematology in Shandong University, Deputy Director of Hematology Department, dedicated to immunomodulatory therapy of aplastic anemia and hematological malignancies.

In 2012, the team became a post-doctoral mobile station, cultivating 4 postdocs, 27 doctoral students and 34 master students. Together, they work tirelessly to immunotherapy of hematologic neoplasm and stem cell basic and clinical application research.

 

Research Areas:

Shandong University-Karolinska Institutet Collaborative Laboratory for Stem Cell Research specializes in developing a curative approach for inherited immune defects by transplantation of autologous hematopoietic stem cells (HSC) derived from iPSC or MSC after correction of disease gene mutations. The collaborations also work on stem cell-based 3-D renal tissue regeneration, aiming to develop future stem cell-based cell therapies for kidney failure. Hence, the research directions are:

1) Regulation of stem cell (iPSC and MSC) differentiation and bio-safety evaluation of in vitro manipulated stem cells.

2) Development and functional evaluation of stem cell-based renal tissue regeneration.

 

Research Achievements:

Under the guidance of relevant national policies and regulations, autologous and allogeneic hematopoietic stem cell transplantation was started in 2004. To achieve better therapeutic effect, since May 2009, we formulated the working system and process for the application of MSCs, published clinical trial of MSCs treatment on the NCBI website, and conducted basic and clinical studies based on MSCs. We found that MSCs has achieved good therapeutic effects in diabetes mellitus, ankylosing spondylitis, pulmonary interstitial fibrosis and severe pneumonia.

In the past five years, our team has published more than 20 SCI papers, with a total funding of 5 million yuan, authorized 5 national invention patents and 2 clinical trials. In 2023, we won the second prize of Science and Technology Progress of Shandong Province.

 

Main Publications:

  1. Hui Li, Dexiao Kong, Yi Zhao, Xia Liu, Fang Xiao, Xiaoyan Li, Jianting Hu, Yingjie Chen, Shengli Li, Baozhu Wang, Yuan Chen, Yang Jiang, Xiaoli Liu, Xiumei Fen, Yanan Guo, Xiaoli Feng, Jing Ren, Fang Wang, Ying Han, William Donelan, Lijun Yang, Dawei Xu, Dongqi Tang, Chengyun Zheng. Irisin protected hemopoietic stem cells and improved outcome of severe bone marrow failure. Biomed Pharmacother. 2023:169:115863.

  2. Jing Ren, Xiumei Feng, Yanan Guo, Dexiao Kong, Yongjing Wang, Juan Xiao, Wen Jiang, Xiaoli Feng, Xiaoli Liu, Ai Li, Congcong Sun, Mingming He, Bingen Li, Juandong Wang, Yang Jiang, Chengyun Zheng. GSK-3β/β-catenin pathway plays crucial roles in the regulation of NK cell cytotoxicity against myeloma cells. FASEB J. 2023;37(3):e22821.

  3. Liyuan Liu, Haixia Liu, Xiaowen Huang, Xiaoli Liu, Chengyun Zheng. A High-Throughput and Uniform Amplification Method for Cell Spheroids. Micromachines (Basel). 2022;13(10):1645.

  4. Wen Jiang, Fanglin Li , Yang Jiang, Shengli Li , Xiaoli Liu, Yaqi Xu, Binggen Li, Xiaoli Feng and Chengyun Zheng. Tim-3 Blockade Elicits Potent Anti-Multiple Myeloma Immunity of Natural Killer Cells. Front Oncol. 2022;12:739976.

  5. Xiaoli Liu, Huichao Lin, Jiaao Song, Taiyi Zhang, Xiaoying Wang, Xiaowen Huang, Chengyun Zheng. A Novel SimpleDrop Chip for 3D Spheroid Formation and Anti-Cancer Drug Assay. Micromachines (Basel). 2021;12(6):681.

  6. Li R, Zheng C, Wang Q, Bi E, Yang M, Hou J, Fu W, Yi Q, Qian J. Identification of an immunogenic DKK1 long peptide for immunotherapy of human multiple myeloma. Haematologica. 2021;106(3):838-846. (Co-corresponding author)

  7. Yang Jiang, Shuo Li, Qian Zhou, Shenghou Liu, Xiaoli Liu, Juan Xiao, Wen Jiang, Yaqi Xu, Dexiao Kong, Fang Wang, Fengtao Wei, Chengyun Zheng. PDCD4 Negatively Regulated Osteogenic Differentiation and Bone Defect Repair of Mesenchymal Stem Cells Through GSK-3β/β-Catenin Pathway. Stem Cells Dev. 2021;30(16):806-815.

  8. Yaqi Xu, Xiaoli Feng, Qian Zhou, Wen Jiang, Yibo Dai, Yang Jiang, Xiaoli Liu, Shuo Li, Yongjing Wang, Fang Wang, Ai Li, and Chengyun Zheng. Novel Small Molecular Compound AE-848 Potently Induces Human Multiple Myeloma Cell Apoptosis by Modulating the NF-κB and PI3K/Akt/mTOR Signaling Pathways. Onco Targets Ther. 2020; 13: 13063–13075.

  9. Xu Y, Zhou Q, Feng X, Dai Y, Jiang Y, Jiang W, Liu X, Xing X, Wang Y, Ni Y, Zheng C. Disulfiram/copper markedly induced myeloma cell apoptosis through activation of JNK and intrinsic and extrinsic apoptosis pathways.Biomed Pharmacother. 2020;126:110048.

  10. Xiaoyan Zhou, Xiaoli Liu, Li Liu, Chao Han, Zhaohong Xie, Xiangtian Liu, Yingying Xu, Fan Li, Jianzhong Bi, Chengyun Zheng. Transplantation of IFN-γ Primed hUCMSCs Significantly Improved Outcomes of Experimental Autoimmune Encephalomyelitis in a Mouse Model. Neurochem Res. 2020;45(7):1510-1517.

     

Facilities & Resources:

Our state-of-the-art facilities and cutting-edge technology enable us to conduct research that is both rigorous and innovative. Our team relies on Institute of Biotherapy for Hematological Malignancies of Shandong University, Institute of Medical Sciences in the Second Hospital of Shandong University and the Animal Laboratory. We have independent ventilation, thousand level clean GMP laboratory and SPF animal experimental center, which have reached the national clean standard. We have complete and advanced instruments, such as flow cytomeometer, fluorescence confocal microscope, fluorescence quantitative PCR instrument, American Abbott drug concentration detector, ultrasonic fragmentation, low temperature high-speed centrifuge, horizontal and vertical electrophoresis imaging and observation system, immunoenzyme linked immunosorbent assay, CO2 cell incubator, ultra-clean working table, biological safety cabinet, -80℃ refrigerator, inverted microscope, fluorescence microscope and cell culture and frozen storage facilities, automatic blood coagulator, freezing microtome, paraffin microtome, automatic tissue dehydrator, small animal living imaging and other advanced instruments and equipments, which meeting the need for the facilities and sites for conducting scientific research.

 

Collaborations & Partnerships:

We believe in the power of collaboration. At present, our team has performed high-quality visits and academic exchanges for more than 10 times, several members have gone to KI to strengthen cooperation and exchange, and Professor Anders Hemstem, Professor Nailin Li, and Professor Magnus Nordenskjold have also visited the Second Hospital of Shandong University for academic lectures and subject cooperation. We have performed academic discussions with Professor Dawei Xu of KI every year, and have sent many visiting scholars to KI for exchange and study.

Moreover, our laboratory and the Institute of Zoology in the Chinese Academy of Sciences established a special clinical research base of strategic stem cell and regenerative medicine research of the Chinese Academy of Sciences. At present, our laboratory has sent several researchers to the Institute of Zoology in the Chinese Academy of Sciences to learn new technologies. And our laboratory also conducted a wide range of academic exchanges and subject cooperation with Beijing Xuanwu hospital, Qilu hospital, Shandong provincial hospital, Shandong University of Chinese medicine and other high level academic and medical unit.


Recreational Activities:

In 2018, the Second Hospital of Shandong University has successfully obtained the right to hold the 8th Chinese Annual Conference of Stem Cell. With the theme of "The research and transformation of stem cells--the new Era", 6 academicians, nearly 100 top scholars and experts, more than 2000 researchers of stem cells across China, gathered together to talk about the frontier.

Take this opportunity, Prof. Yibiao Wang and Chengyun Zheng established The Stem Cell Association of Shandong Provincial and held the first annual meeting. Then, academic conferences are held every year, and the association is gradually developed to have fifth professional committee, promoting the development of stem cells in our province and even the whole country.

 

Other Features:

Our team is characterized by cell immunotherapy, and the clinical research of stem cells and immune cells, and has a certain influence in the whole country. Our outstanding advantages are as follows: 1) NK cell functional regulation, CAR-T / CAR-NK immune cells for hematological malignancies (B cell tumors, multiple myeloma, leukemia); 2) various types of hematopoietic stem cell transplantation for hematological tumors, bone marrow failure disease or genetic immune deficiency disease; 3) treatment and prevention of MSCs for GVHD and related complications; 4) treatment of MSCs for severe infection and bone marrow failure.

 

Contact:

For more information or inquiries, please contact us at sdeyzcy@email.sdu.edu.cn

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