Scalable Generation of Universal Platelets from Human Induced Pluripotent Stem Cells

被引：169

作者：

Feng, Qiang ^{[1
]}

Shabrani, Namrata ^{[2
]}

Thon, Jonathan N. ^{[3
,4
]}

Huo, Hongguang ^{[1
]}

Thiel, Austin ^{[1
]}

Machlus, Kellie R. ^{[3
,4
]}

Kim, Kyungho ^{[2
]}

Brooks, Julie ^{[1
]}

Li, Feng ^{[1
]}

Luo, Chenmei ^{[1
]}

Kimbrel, Erin A. ^{[1
]}

Wang, Jiwu ^{[6
]}

Kim, Kwang-Soo ^{[7
]}

Italiano, Joseph ^{[3
,4
,5
]}

Cho, Jaehyung ^{[2
]}

Lu, Shi-Jiang ^{[1
]}

Lanza, Robert ^{[1
]}

机构：

[1] Adv Cell Technol, Marlborough, MA 01752 USA

[2] Univ Illinois, Coll Med, Dept Pharmacol, Chicago, IL 60612 USA

[3] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Boston, MA 02115 USA

[5] Boston Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA

[6] Allele Biotechnol, San Diego, CA 92121 USA

[7] Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02478 USA

来源：

STEM CELL REPORTS | 2014年 / 3卷 / 05期

关键词：

IN-VITRO; HEMATOPOIETIC PROGENITORS; DIFFERENTIATION CULTURES; FUNCTIONAL PLATELETS; MEGAKARYOCYTE; MOUSE; REFRACTORINESS; TRANSFUSION; EXPRESSION; DERIVATION;

D O I：

10.1016/j.stemcr.2014.09.010

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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 beta 2-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.

引用

页码：817 / 831

页数：15

共 46 条

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