Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Metalloproteinase regulation improves in vitro generation of efficacious platelets from mouse embryonic stem cells

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Nishikii, H.
  • Eto, K.
  • Tamura, N.
  • Hattori, K.
  • Heissig, B.
  • Kanaji, Taisuke
  • Sawaguchi, A.
  • Goto, S.
  • Ware, J.
  • Nakauchi, H.

publication date

  • August 2008

journal

  • Journal of Experimental Medicine  Journal

abstract

  • Embryonic stem cells (ESCs) could potentially compensate for the lack of blood platelets available for use in transfusions. Here, we describe a new method for generating mouse ESC-derived platelets (ESPs) that can contribute to hemostasis in vivo. Flow cytometric sorting of cells from embryoid bodies on day 6 demonstrated that c-Kit(+) integrin alpha IIb (alpha IIb)(+) cells, but not CD31(+) cells or vascular endothelial cadherin(+) cells, are capable of megakaryopoiesis and the release of platelet-like structures by day 12. alpha IIb beta 3-expressing ESPs exhibited ectodomain shedding of glycoprotein (GP)Ibalpha, GPV, and GPVI, but not alpha IIb beta 3 or GPIb beta. ESPs showed impaired alpha IIb beta 3 activation and integrin-mediated actin reorganization, critical events for normal platelet function. However, the administration of metalloproteinase inhibitors GM6001 or TAPI-1 during differentiation increased the expression of GPIb alpha, improving both thrombogenesis in vitro and posttransfusion recovery in vivo. Thus, the regulation of metalloproteinases in culture could be useful for obtaining high-quality, efficacious ESPs as an alternative platelet source for transfusions.

subject areas

  • Animals
  • Blood Platelets
  • Cells, Cultured
  • Dipeptides
  • Embryonic Stem Cells
  • In Vitro Techniques
  • Integrin beta3
  • Megakaryocytes
  • Metalloproteases
  • Mice
  • Platelet Glycoprotein GPIb-IX Complex
  • Platelet Membrane Glycoprotein IIb
  • Protease Inhibitors
  • Proto-Oncogene Proteins c-kit
  • Thrombopoiesis
  • Thrombosis
scroll to property group menus

Identity

PubMed Central ID

  • PMC2525582

International Standard Serial Number (ISSN)

  • 0022-1007

Digital Object Identifier (DOI)

  • 10.1084/jem.20071482

PubMed ID

  • 18663123
scroll to property group menus

Additional Document Info

start page

  • 1917

end page

  • 1927

volume

  • 205

issue

  • 8

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support