title: Integrated Biophysical and Biochemical Signals Augment Megakaryopoiesis and Thrombopoiesis in a Three-Dimensional Rotary Culture System.
abstract: Platelet transfusion has been widely used in patients undergoing chemotherapy or radiotherapy; however, the shortage of the platelet supply limits the care of patients. Although derivation of clinical-scale platelets in vitro could provide a new source for transfusion, the devices and procedures for deriving scalable platelets for clinical applications have not been established. In the present study, we found that a rotary cell culture system (RCCS) can potentiate megakaryopoiesis and significantly improve the efficiency of platelet generation. When used with chemical compounds and growth factors identified via small-scale screening, the RCCS improved platelet generation efficiency by as much as ∼3.7-fold compared with static conditions. Shear force, simulated microgravity, and better diffusion of nutrients and oxygen from the RCCS, altogether, might account for the improved efficient platelet generation. The cost-effective and highly controllable strategy and methodology represent an important step toward large-scale platelet production for future biomedical and clinical applications. Significance: Platelet transfusion has been widely used in patients undergoing chemotherapy or radiotherapy; however, the shortage of platelet supply limits the care of patients. Thus, derivation of clinical-scale platelets in vitro would provide a new source for transfusion. The present study evaluated a rotary suspension cell culture system that was able to potentiate megakaryopoiesis and significantly improved the efficiency of platelet generation. When used with chemical compounds and growth factors identified via small-scale screening, the three-dimensional system improved platelet generation efficiency compared with the static condition. The three-dimensional device and the strategy developed in the present study should markedly improve the generation of large-scale platelets for use in future biomedical and clinical settings.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, and Department of Stem Cells and Regenerative Medicine, Peking Union Medical College, Tianjin, People's Republic of China Faculty of Laboratory Medical Science, Hebei North University, Zhangjiakou, People's Republic of China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, and Department of Stem Cells and Regenerative Medicine, Peking Union Medical College, Tianjin, People's Republic of China.
authors.forename: CuiCui
authors.initials: C
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, CAS, Beijing, People's Republic of China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Lei
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, and Department of Stem Cells and Regenerative Medicine, Peking Union Medical College, Tianjin, People's Republic of China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, and Department of Stem Cells and Regenerative Medicine, Peking Union Medical College, Tianjin, People's Republic of China.
authors.forename: Pei
authors.initials: P
authors.lastname: Su
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, and Department of Stem Cells and Regenerative Medicine, Peking Union Medical College, Tianjin, People's Republic of China.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Ru
authors.affiliation: Department of Cardiovascular Surgery, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Ruan
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, CAS, Beijing, People's Republic of China.
authors.forename: Enkui
authors.initials: E
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, and Department of Stem Cells and Regenerative Medicine, Peking Union Medical College, Tianjin, People's Republic of China.
authors.forename: Sizhou
authors.initials: S
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, and Department of Stem Cells and Regenerative Medicine, Peking Union Medical College, Tianjin, People's Republic of China.
authors.forename: Mingzhe
authors.initials: M
authors.lastname: Han
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, and Department of Stem Cells and Regenerative Medicine, Peking Union Medical College, Tianjin, People's Republic of China.
authors.forename: Yuanfu
authors.initials: Y
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, and Department of Stem Cells and Regenerative Medicine, Peking Union Medical College, Tianjin, People's Republic of China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, and Department of Stem Cells and Regenerative Medicine, Peking Union Medical College, Tianjin, People's Republic of China jiangerlie@163.com zhoujx@ihcams.ac.cn.
authors.forename: Erlie
authors.initials: E
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, and Department of Stem Cells and Regenerative Medicine, Peking Union Medical College, Tianjin, People's Republic of China jiangerlie@163.com zhoujx@ihcams.ac.cn.
authors.forename: Jiaxi
authors.initials: J
authors.lastname: Zhou
mesh_terms: D028341:Activins / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018929:Cell Culture Techniques / Q000191:economics / Q000295:instrumentation; D002469:Cell Separation; D003362:Cost-Benefit Analysis; D004058:Diffusion; D004149:Dioxoles / Q000494:pharmacology; D004867:Equipment Design; D005312:Fetal Blood / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D057166:High-Throughput Screening Assays; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008533:Megakaryocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012212:Rheology; D015398:Signal Transduction; D034061:Thrombopoiesis / Q000187:drug effects / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology; D018474:Weightlessness Simulation
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D000577:Amides; D001549:Benzamides; D015415:Biomarkers; D004149:Dioxoles; D036341:Intercellular Signaling Peptides and Proteins; D011725:Pyridines; C422405:activin A; D028341:Activins; C108830:Y 27632; D014212:Tretinoin; D010100:Oxygen
keywords: CD34+ cell; Megakaryopoiesis; Rotary suspension culture; Thrombopoiesis