Humanized large-scale expanded endothelial colony-forming cells function in vitro and in vivo.

Abstract:

:Endothelial progenitor cells are critically involved in essential biologic processes, such as vascular homeostasis, regeneration, and tumor angiogenesis. Endothelial colony-forming cells (ECFCs) are endothelial progenitor cells with robust proliferative potential. Their profound vessel-forming capacity makes them a promising tool for innovative experimental, diagnostic, and therapeutic strategies. Efficient and safe methods for their isolation and expansion are presently lacking. Based on the previously established efficacy of animal serum-free large-scale clinical-grade propagation of mesenchymal stromal cells, we hypothesized that endothelial lineage cells may also be propagated efficiently following a comparable strategy. Here we demonstrate that human ECFCs can be recovered directly from unmanipulated whole blood. A novel large-scale animal protein-free humanized expansion strategy preserves the progenitor hierarchy with sustained proliferation potential of more than 30 population doublings. By applying large-scale propagated ECFCs in various test systems, we observed vascular networks in vitro and perfused vessels in vivo. After large-scale expansion and cryopreservation phenotype, function, proliferation, and genomic stability were maintained. For the first time, proliferative, functional, and storable ECFCs propagated under humanized conditions can be explored in terms of their therapeutic applicability and risk profile.

journal_name

Blood

journal_title

Blood

authors

Reinisch A,Hofmann NA,Obenauf AC,Kashofer K,Rohde E,Schallmoser K,Flicker K,Lanzer G,Linkesch W,Speicher MR,Strunk D

doi

10.1182/blood-2008-09-181362

subject

Has Abstract

pub_date

2009-06-25 00:00:00

pages

6716-25

issue

26

eissn

0006-4971

issn

1528-0020

pii

blood-2008-09-181362

journal_volume

113

pub_type

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