High-level transgene expression in induced pluripotent stem cell-derived megakaryocytes: correction of Glanzmann thrombasthenia.

Blood
Spencer K SullivanPaul Gadue

Abstract

Megakaryocyte-specific transgene expression in patient-derived induced pluripotent stem cells (iPSCs) offers a new approach to study and potentially treat disorders affecting megakaryocytes and platelets. By using a Gp1ba promoter, we developed a strategy for achieving a high level of protein expression in human megakaryocytes. The feasibility of this approach was demonstrated in iPSCs derived from two patients with Glanzmann thrombasthenia (GT), an inherited platelet disorder caused by mutations in integrin αIIbβ3. Hemizygous insertion of Gp1ba promoter-driven human αIIb complementary DNA into the AAVS1 locus of iPSCs led to high αIIb messenger RNA and protein expression and correction of surface αIIbβ3 in megakaryocytes. Agonist stimulation of these cells displayed recovery of integrin αIIbβ3 activation. Our findings demonstrate a novel approach to studying human megakaryocyte biology as well as functional correction of the GT defect, offering a potential therapeutic strategy for patients with diseases that affect platelet function.

References

May 25, 2011·Proceedings of the National Academy of Sciences of the United States of America·Juan FangDavid A Wilcox
Jan 19, 2012·Haemophilia : the Official Journal of the World Federation of Hemophilia·M FioreA T Nurden
Jun 29, 2012·Haemophilia : the Official Journal of the World Federation of Hemophilia·A T NurdenU Seligsohn
Oct 10, 2012·Proceedings of the National Academy of Sciences of the United States of America·Stella T ChouMitchell J Weiss
Nov 15, 2012·Journal of Visualized Experiments : JoVE·Andreia Gianotti SommerGustavo Mostoslavsky
Jul 23, 2013·Hämostaseologie·V WiegeringP G Schlegel
Aug 13, 2013·Nature·Alejandra Sanjuan-PlaSten Eirik W Jacobsen

❮ Previous
Next ❯

Citations

Jan 17, 2019·Tissue Engineering. Part a·H Isaac ChenDouglas H Smith
Oct 7, 2017·Current Opinion in Hematology·Kandace GollompMortimer Poncz
Jul 16, 2014·Current Opinion in Hematology·Brenden W Smith, George J Murphy
Jul 8, 2015·Journal of Thrombosis and Haemostasis : JTH·R LydeM Poncz
Jun 7, 2019·Disease Models & Mechanisms·Maria Georgomanoli, Eirini P Papapetrou
May 26, 2018·Platelets·Andrew L Frelinger
Oct 7, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Sara BorstPaul Gadue

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Cell Fate Conversion By mRNA

mRNA-based technology is being studied as a potential technology that could be used to reprogram cell fate. This technique provides the potential to generate safe reprogrammed cells that can be used for clinical applications. Here is the latest research on cell fate conversion by mRNA.