Expandable Megakaryocyte Cell Lines Enable Clinically Applicable Generation of Platelets from Human Induced Pluripotent Stem Cells

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• 作者：Sou Nakamura¹ ; Naoya Takayama¹ ; Shinji Hirata¹ ; Hideya Seo¹ ; Hiroshi Endo¹ ; Kiyosumi Ochi¹ ; Ken-ichi Fujita¹ ; Tomo Koike¹ ; Ken-ichi Harimoto¹ ; Takeaki Dohda¹ ; Akira Watanabe² ; Keisuke Okita² ; Nobuyasu Takahashi³ ; Akira Sawaguchi³ ; Shinya Yamanaka² ; Hiromitsu Nakauchi⁴ ; Satoshi Nishimura⁵ ; ⁶ ; Koji Eto¹ ; ⁴ ; ^{kojieto@cira.kyoto-u.ac.jp" class="auth_mail}
• 刊名：Cell Stem Cell
• 出版年：3 April, 2014
• 年：2014
• 卷：14
• 期：4
• 页码：535-548
• 全文大小：3886 K

文摘

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Summary

The donor-dependent supply of platelets is frequently insufficient to meet transfusion needs. To address this issue, we developed a clinically applicable strategy for the derivation of functional platelets from human pluripotent stem cells (PSCs). This approach involves the establishment of stable immortalized megakaryocyte progenitor cell lines (imMKCLs) from PSC-derived hematopoietic progenitors through the overexpression of BMI1 and BCL-XL to respectively suppress senescence and apoptosis and the constrained overexpression of c-MYC to promote proliferation. The resulting imMKCLs can be expanded in culture over extended periods (4-5聽months), even after cryopreservation. Halting the overexpression of c-MYC, BMI1, and BCL-XL in growing imMKCLs led to the production of CD42b⁺ platelets with functionality comparable to that of native platelets on the basis of a range of assays in聽vitro and in聽vivo. The combination of robust expansion capacity and efficient platelet production means that appropriately selected imMKCL clones represent a potentially inexhaustible source of hPSC-derived platelets for clinical application.