RRC ID 44410
Author Nakagawa Y, Nakamura S, Nakajima M, Endo H, Dohda T, Takayama N, Nakauchi H, Arai F, Fukuda T, Eto K.
Title Two differential flows in a bioreactor promoted platelet generation from human pluripotent stem cell-derived megakaryocytes.
Journal Exp. Hematol.
Abstract Induced pluripotent stem cell (iPSC) technology enables us to investigate various potential iPSC-based therapies. Although the safety of iPSC derivation has not been completely validated, anucleate cells, such as platelets or erythrocytes, derived from iPSCs are promising targets. However, the efficiency of in vitro platelet generation from megakaryocytes (MKs) under static culture conditions is lower than is seen in vivo. In this study, we demonstrate the proof of concept by a two-dimensional flow culture system that enabled us to increase platelet yield from human embryonic stem cell or iPSC-derived MKs using a biomimetic artificial blood vessel system. The bioreactor was composed of biodegradable scaffolds with ordered arrays of pores made to mimic in vivo bone marrow through salt leaching. Within the system, two flows in different directions in which the angle between the directions of flow is 60 degrees but not 90 degrees contributed to suitable pressure and shear stress applied to MKs to promote platelet generation. Generated platelets derived from human embryonic stem cells or human induced pluripotent stem cells through the bioreactor with a 60-degree angle revealed intact integrin αIIbβ3 activation after agonist stimulation. Collectively, our findings indicate that two flows in different directions of two-dimensional flow culture may be a feasible system for in vitro generation of platelets from pluripotent stem cells (i.e., iPSC-derived MKs) in numbers sufficient for transfusion therapy.
Volume 41(8)
Pages 742-8
Published 2013-8
DOI 10.1016/j.exphem.2013.04.007
PII S0301-472X(13)00165-3
PMID 23618622
MeSH Biomimetics Bioreactors* Blood Platelets / cytology* Cell Culture Techniques Humans Megakaryocytes / cytology* Pluripotent Stem Cells / cytology*
IF 2.436
Times Cited 36
WOS Category MEDICINE, RESEARCH & EXPERIMENTAL HEMATOLOGY
Resource
Human and Animal Cells