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
Author Information
Qiang Feng: Advanced Cell Technology, Marlborough, MA 01752, USA.
Namrata Shabrani: Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA.
Jonathan N Thon: Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115.
Hongguang Huo: Advanced Cell Technology, Marlborough, MA 01752, USA.
Austin Thiel: Advanced Cell Technology, Marlborough, MA 01752, USA.
Kellie R Machlus: Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115.
Kyungho Kim: Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA.
Julie Brooks: Advanced Cell Technology, Marlborough, MA 01752, USA.
Feng Li: Advanced Cell Technology, Marlborough, MA 01752, USA.
Chenmei Luo: Advanced Cell Technology, Marlborough, MA 01752, USA.
Erin A Kimbrel: Advanced Cell Technology, Marlborough, MA 01752, USA.
Jiwu Wang: Allele Biotechnology, San Diego, CA 92121, USA.
Kwang-Soo Kim: MacLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
Joseph Italiano: Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115; Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Boston, MA 02115, USA.
Jaehyung Cho: Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA.
Shi-Jiang Lu: Advanced Cell Technology, Marlborough, MA 01752, USA.
Robert Lanza: Advanced Cell Technology, Marlborough, MA 01752, USA. Electronic address: rlanza@advancedcell.com.
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 β2-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.
