Scalable generation.pdf (4.48 MB)
Download fileScalable Generation of Universal Platelets from Human Induced Pluripotent Stem Cells
journal contribution
posted on 2016-01-29, 00:00 authored by 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 LanzaHuman 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.