Transfusionsmedizin 2011; 1: 1-13
DOI: 10.1055/s-0031-1283704
CME-Fortbildung

© Georg Thieme Verlag KG Stuttgart ˙ New York

Endothelial Colony-forming Progenitor Cells: Identification, Isolation, Expansion and Potential Use for Regenerative Cell Therapy

Endotheliale koloniebildende Progenitorzellen: Identifikation, Isolierung, Expansion und potenzieller klinischer Einsatz für regenerative ZelltherapieE. Rohde1
  • 1Universitätsklinik für Blutgruppenserologie und Transfusionsmedizin der Paracelsus Medizinische Privatuniversität, Salzburger Landeskliniken
Further Information

Publication History

Publication Date:
14 September 2011 (online)

Abstract

Regenerative medicine is an emerging therapeutic approach which is based on the clinical application of adult stem cells for the repair of organs after toxic, metabolic or ischemic organ injury. Upcoming therapeutic options in regenerative medicine will bring profound challenges for the field of transfusion medicine with regards to new technologies in cell or tissue manipulation and multidisciplinary clinical efforts. In cooperation with hematologists, the teams at trans­fusion medicine departments have been concerned with the identification, isolation and storage of hematopoietic progenitor cells for therapeutic application since more than 20 years. A crucial factor for the successful regeneration of organs after damage due to non-neoplastic reasons is the reconstitution of the functional vascular situation providing sufficient blood perfusion of the target tissues. For this reason clinical research has increasingly focused at circulating endothelial progenitor cells since 15 years. This short article introduces recent findings on “endo­thelial colony-forming progenitor cells (ECFC)” highlighting the role of central actors in post­natal neo-vasculogenesis. 

Zusammenfassung

Die „regenerative Medizin“ beschäftigt sich mit der Anwendung von adulten Stammzellen im menschlichen Organismus zur Reparatur von ischämisch, toxisch oder metabolisch geschädigten Geweben und Organen. Dieser innovative therapeutische Ansatz hat grundlegende Aus­wirkungen auf die Transfusionsmedizin. Gemeinsam mit den Hämatologen sind Transfusionsmediziner seit über 20 Jahren damit beschäftigt, hämatopoetische Stammzellen zu identifizieren, zu isolieren und zu lagern und entweder im autologen oder allogenen Setting therapeutisch einzusetzen. Bei der Anwendung adulter Stammzellen nicht hämatpoetischen Ursprungs für die Regeneration von nicht neoplastisch geschädigtem Gewebe ist die funktionsfähige Durchblutung des Zielgewebes ein wesentlicher Faktor. Daher sind die für Gefäßregeneration nötigen zirkulierenden endothelialen Progenitorzellen seit etwa 15 Jahren verstärkt im Fokus der klinischen Forschung. Dieser Kurzartikel stellt neue Erkenntnisse über „endotheliale, koloniebildenden Progenitorzellen“ als zentral involvierte Akteure der postnatalen Neovaskulogenese vor. 

References

  • 1 Gurley K A, Sanchez Alvarado A ed. Stem cells in animal models of regeneration, Stem Book. The Stem Cell Research Community, StemBook 2008 DOI: doi/10.3824/stembook.1.32.1 http://http://www.stembook.org
  • 2 Khademhosseini A, Vacanti J P, Langer R. Progress in Tissue Engineering.  Scientific American. 2009;  300 ( (5)) 64-71
  • 3 Bouvier C A, Gaynor E, Cintron J R. Circulating Endothelium As An Indication of Vascular Injury.  Thrombosis et Diathesis Haemorrhagica. 1970;  40 163-168
  • 4 ngram D A, Caplice N M, Yoder M C. Unresolved questions, changing definitions, and novel paradigms for ­defining endothelial progenitor cells.  Blood. 2005;  106 1525-1531
  • 5 Ingram D A et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood.  Blood. 2004;  104 2752-2760
  • 6 Reinisch A et al. Humanized large-scale expanded endothelial colony-forming cells function in vitro and in vivo.  Blood. 2009;  113 6716-6725
  • 7 Fadini G P et al. Technical notes on endothelial progenitor cells: Ways to escape from the knowledge plateau.  Atherosclerosis. 2008;  197 496-503
  • 8 Hirschi K K, Ingram D A, Yoder M C. Assessing identity, phenotype, and fate of endothelial progenitor cells.  Arteriosclerosis Thrombosis and Vascular Biology. 2008;  28 1584-1595
  • 9 Duda D G, Cohen K S, Scadden D T et al. A protocol for phenotypic detection and enumeration of circulating endothelial cells and circulating progenitor cells in human blood.  Nature Protocols. 2007;  2 805-810
  • 10 Mancuso P et al. Validation of a Standardized Method for Enumerating Circulating Endothelial Cells and Progenitors: Flow Cytometry and Molecular and Ultrastructural Analyses.  Clinical Cancer Research. 2009;  15 267-273
  • 11 Woywodt A et al. Isolation and enumeration of circulating endothelial cells by immunomagnetic isolation: proposal of a definition and a consensus protocol.  Journal of Thrombosis and Haemostasis. 2006;  4 671-677
  • 12 Case J et al. Human CD34(+)AC133(+)VEGFR-2(+) cells are not endothelial progenitor cells but distinct, primitive hematopoietic progenitors.  Experimental Hematology. 2007;  35 1109-1118
  • 13 Lin Y, Weisdorf D, Solovey A et al. Origins of circulating endothelial cells and endothelial outgrowth from blood.  Journal of Clinical Investigation. 2000;  105 71-77
  • 14 Schallmoser K et al. Human platelet lysate can replace fetal bovine serum for clinical-scale expansion of functional mesenchymal stromal cells.  Transfusion. 2007;  47 1436-1446
  • 15 Rohde E et al. Blood monocytes mimic endothelial progenitor cells.  Stem Cells. 2006;  24 357-367
  • 16 Stout R D, Suttles J. Functional plasticity of macrophages: reversible adaptation to changing microenvironments.  Journal of Leukocyte Biology. 2004;  76 509-513
  • 17 Luttun A, Verfaillie C M. Will the real EPC please stand up?.  Blood. 2007;  109 1795-1796
  • 18 Shintani S et al. Mobilization of endothelial progenitor cells in patients with acute myocardial infarction.  Circulation. 2001;  103 2776-2779
  • 19 Asahara T et al. Isolation of putative progenitor endothelial cells for angiogenesis.  Science. 1997;  275 964-967
  • 20 Assmus B et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial ­infarction – (TOPCARE-AMI).  Circulation. 2002;  106 3009-3017
  • 21 Hill J M et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk.  New England Journal of Medicine. 2003;  348 593-600
  • 22 Rohde E et al. Immune cells mimic the morphology of endothelial progenitor colonies in vitro.  Stem Cells. 2007;  25 1746-1752
  • 23 Hur J et al. Identification of a novel role of T cells in postnatal vasculogenesis – Characterization of endothelial progenitor cell colonies.  Circulation. 2007;  116 1671-1682
  • 24 Weber C, Zernecke A, Libby P. The multifaceted contributions of leukocyte subsets to atherosclerosis: lessons from mouse models.  Nature Reviews Immunology. 2008;  8 802-815
  • 25 Melero-Martin J M et al. Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells.  Circulation Research. 2008;  103 194-202
  • 26 Critser P C, Voytik-Harbin S L, Yoder M C. Isolating and defining cells to engineer human blood vessels.  Cell Proliferation. 2011;  44 15-21
  • 27 Yoder M C, Ingram D A. The definition of EPCs and other bone marrow cells contributing to neoangiogenesis and tumor growth: Is there common ground for understanding the roles of numerous marrow-derived cells in the neoangiogenic process?.  Biochimica et Biophysica Acta-Reviews on Cancer. 2009;  1796 50-54

Prim. Univ.-Prof. Dr. E. Rohde

Vorstand der Universitätsklinik für Blutgruppenserologie und Transfusionsmedizin der Paracelsus Medizinische Privatuniversität · Salzburger Landeskliniken

Lindhofstraße 20–22

A-5020 Salzburg

Österreich

Email: e.rohde@salk.at