Scalable generation of universal platelets from human induced pluripotent stem cells

Qiang Feng, Namrata Shabrani, Jonathan N. Thon, Hongguang Huo, Austin Thiel, Kellie R. Machlus, Kyungho Kim, Julie Brooks, Feng Li, Chenmei Luo, Erin A. Kimbrel, Jiwu Wang, Kwang Soo Kim, Joseph Italiano, Jaehyung Cho, Shi Jiang Lu, Robert Lanza

Research output: Contribution to journalArticlepeer-review

177 Scopus citations

Abstract

Human induced pluripotent stem cells (iPSCs) provide a potentially replenishable source for the production of transfusable platelets. Here, we describe a method to generate megakaryocytes (MKs) and functional platelets from iPSCs in a scalable manner under serum/ feeder-free conditions. The method also permits the cryopreservation of MK progenitors, enabling a rapid ''''surge'''' capacity when large numbers of platelets are needed. Ultrastructural/morphological analyses show no major differences between iPSC platelets and human blood platelets. iPSC platelets form aggregates, lamellipodia, and filopodia after activation and circulate in macrophage-depleted animals and incorporate into developing mouse thrombi in a manner identical to human platelets. By knocking out the b2-microglobulin gene, we have generated platelets that are negative for the major histocompatibility antigens. The scalable generation of HLA-ABC-negative platelets from a renewable cell source represents an important step toward generating universal platelets for transfusion as well as a potential strategy for the management of platelet refractoriness.

Original languageEnglish
Pages (from-to)817-831
Number of pages15
JournalStem Cell Reports
Volume3
Issue number5
DOIs
StatePublished - 2014

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