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First published online May 1, 2008
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Submitted on November 23, 2007
Accepted on April 16, 2008

TISSUE-SPECIFIC STEM CELLS

Identification of Hemangioblasts in the Adult Human Adipose Tissue

María Dolores Miñana 1*, Francisco Carbolell-Uberos 2, Vicente Mirabet 3, Severiano Marín 4, Araceli Encabo 1

1 Fundación Hospital General Universitario, Valencia, Spain
2 Servicio de Inmunohematología, Centro de Transfusión de la Comunidad Valenciana, Valencia, Spain
3 Banco de Tejidos, Centro de Transfusión de la Comunidad Valenciana, Valencia, Spain
4 Servicio de Cirugía Plástica y Reparadora, Consorcio Hospital General Universitario, Valencia, Spain

* To whom correspondence should be addressed. E-mail: minyana_mdo{at}gva.es.


   Abstract

Stromal-vascular fraction (SVF) of human adipose tissue contains, among other cell types, mesenchymal stem cells, and precursors of adipocyte and endothelial cells. Here we show that additionally, non-hematopoietic fraction of SVF has hematopoietic activity, since all types of hematopoietic colony-forming units (CFUs) developed when cultured in methylcellulose-based medium. This hematopoietic activity was restricted to CD45-CD105+ cell subset, well correlated with KDR+ cell content, and increased after culture with a combination of early-acting hematopoietic cytokines. Most of CD45-KDR+CD105+ cells were non-adherent, did not express CD31 and included both CD34- and CD34+ cells. Moreover, these non-adherent cells migrated in response to KDR gradient, and when cultured in the presence of both hematopoietic and endothelial growth factors, a first wave of CFUs was followed by a second wave of mixed colonies comprising adherent elongated and non-adherent round hematopoietic cells. These mixed hematopoietic-endothelial (Hem-End) colonies were able to generate secondary Hem-End colonies and exhibited both hematopoietic and endothelial activity, as demonstrated by in vitro functional assays. These findings demonstrate for the first time the existence of primitive mesodermal progenitors within SVF of human adipose tissue that exhibit in vitro hematopoietic and hemangioblastic activities, susceptible to be used in cell therapy and basic cell research.

______________________________________________________________________________

Author contributions: M.M.: Conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; F.C.: Collection of data, data analysis and interpretation, final approval of manuscript; V.M.: Collection of data; S.M.: Provision of study patients, collection of data; A.E.: Collection of data, data analysis and interpretation, final approval of manuscript.

Key Words. hematopoietic stem cells, hemangioblast, adipose tissue







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