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Research Database PMU-SQQUID

Humanized large-scale expanded endothelial colony-forming cells function in vitro and in vivo.
Reinisch, A; Hofmann, NA; Obenauf, AC; Kashofer, K; Rohde, E; Schallmoser, K; Flicker, K; Lanzer, G; Linkesch, W; Speicher, MR; Strunk, D;
Blood. 2009; 113(26): 6716-6725.
Originalarbeiten (Zeitschrift)

PMU-Authors

Rohde Eva
Schallmoser Katharina
Strunk Dirk

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. (Blood. 2009;113:6716-6725)


Useful keywords (using NLM MeSH Indexing)

3T3 Cells/enzymology

Adult

Animals

Cell Culture Techniques/methods*

Cell Division

Cell Separation/methods

Cells, Cultured/cytology

Cells, Cultured/enzymology

Cells, Cultured/transplantation

Clone Cells/cytology

Clone Cells/enzymology

Colony-Forming Units Assay

Cryopreservation

Culture Media

Endothelial Cells/cytology*

Endothelial Cells/enzymology

Fetal Blood/cytology

Hematopoietic Stem Cell Transplantation

Hematopoietic Stem Cells/cytology*

Hematopoietic Stem Cells/enzymology

Humans

Immunophenotyping

Infant, Newborn

Mice

Mice, Nude

Neovascularization, Pathologic/etiology

Neovascularization, Pathologic/pathology

Neovascularization, Physiologic

Telomere/metabolism

Telomere/ultrastructure

Transplantation, Heterologous