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ArticleStem cell reviews and reports2026

Optimizing the Method for Differentiation of Functional Platelets from Human Induced Pluripotent Stem Cells.

Wei Yue, Yue Yang, Yan Miao, Jinqi Li, Shanshan Li, Yi Yang, Yingwen Zhang, Baohua Qian, Yanxin Li, Haihui Gu

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Article in Stem cell reviews and reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

10 authors.

Wei Yue *Department of Transfusion Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China.
Yue Yang *Department of Transfusion Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China.
Yan Miao *Department of Laboratory II, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Jinqi Li *Department of Transfusion Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China.
Shanshan LiKey Laboratory of Pediatric Hematology & Oncology of China Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Yi YangKey Laboratory of Pediatric Hematology & Oncology of China Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Yingwen ZhangKey Laboratory of Pediatric Hematology & Oncology of China Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Baohua QianDepartment of Transfusion Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China.
Yanxin LiKey Laboratory of Pediatric Hematology & Oncology of China Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China. liyanxin@scmc.com.cn.
Haihui GuDepartment of Transfusion Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China. haihuigu@126.com.

Funding

National Natural Science Foundation of China No. 32271007National Natural Science Foundation of China No. 81970165Natural Science Foundation of Shanghai Municipality 23ZR1441000
6 · The paper itself

Abstract

objectiveThe global shortage of platelets presents a significant challenge in healthcare. Although human induced pluripotent stem cells (hiPSCs) offer a renewable source for ex vivo platelet production, the current approach remains constrained by heterogeneity, low yield, and high costs. This study introduces an optimized differentiation scheme (ODS) to improve ex vivo platelet differentiation from hiPSCs.

methodsA systematically optimized culture protocol was developed, incorporating: (1) a higher initial dose of embryoid body (EB) cells, (2) refining culture medium, (3) substitution of cytokines with small molecules, and (4) enhancement of megakaryocyte (MK) polyploidization via small-molecule supplementation. Feasibility and effectiveness were evaluated using microscopy, cell counting, flow cytometry, Wright-Giemsa staining, immunofluorescence (IF), and transmission electron microscopy (TEM).

resultsIncreasing the initial EB cell count significantly promoted megakaryocyte production and accelerated the process. A serum-free medium supplemented with human platelet lysate (HPL) was favorable for megakaryocyte generation. Small molecules 740Y-P and butyzamide effectively substituted SCF and TPO for differentiation, while the combination of blebbistatin and 616452 enhanced megakaryocyte maturation. Mature megakaryocytes continuously generated functional platelets that, upon thrombin activation, facilitated fibrin clot formation and contraction in vitro. This method shortened differentiation to 19 days, enhanced output to 1.42 CD41⁺ megakaryocytes and 14.9 platelets per iPSC, and reduced costs by 58.3%.

conclusionWe have established a cost-effective strategy for platelet production via hiPSC differentiation, with potential applications in cell therapy and gene editing.

Indexed as

Blood PlateletsCell Culture TechniquesCell DifferentiationInduced Pluripotent Stem CellsCells, CulturedCulture Media, Serum-FreeEmbryoid BodiesHumansMegakaryocytesThrombopoiesisCulture Media, Serum-FreeDifferentiationInduced Pluripotent Stem Cell (iPSC)Megakaryocyte (MK)Thrombopoiesis

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