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Scalable Generation of Universal Platelets from Human Induced Pluripotent Stem Cells

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posted on 29.01.2016 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 Lanza
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.

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This research was partially supported by NIH grants 1RC4HL106627-01 (R.L. and K.S.K.) and HL109439 (J.C.). Q.F., H.H., A.T., J.B., F.L., C.L., E.A.K., S.J.L., and R.L. are employees of Advanced Cell Technology, a biotechnology company in the field of stem cells and regenerative medicine. J.N.T. and J.I. are founders of Platelet BioGenesis.

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Publisher Statement

This is the copy of an article published in Stem Cell Reports © 2014 Elsevier Stem Cell Reports. 2014. 3(5): 817-831. DOI: 10.1016/j.stemcr.2014.09.010.

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Elsevier

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11/11/2014

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