Hepatocyte-conditioned medium sustains endothelial differentiation of human hematopoietic-endothelial progenitors

Veronica Bordoni, Tonino Alonzi, Lucia Zanetta, Daniele Khouri, Annarita Conti, Marco Corazzali, Francesco Bertolini, Pierluigi Antoniotti, Giuseppe Pisani, Francesca Tognoli, Elisabetta Dejana, Marco Tripodi

Research output: Contribution to journalArticle

Abstract

Liver neo-angiogenesis plays a fundamental role in physiological and pathological processes such as regeneration, cirrhosis, autoimmune hepatitis, and alcoholic liver disease. How liver parenchymal cells influence angiogenesis is largely unknown. We studied the influence of soluble factors released by hepatocytes on hematopoietic and endothelial cell differentiation. Human CD34+ cells cultured for several weeks in a hepatocyte-conditioned medium gradually decrease the expression of CD34 and CD133 markers (i.e. after 4 weeks from 85% and 69%, respectively, to 6% and 3%, respectively), whereas expression of CD144 and CD14 cell markers increased (from 2% and 8%, respectively, to 54% and 55%, respectively). The cells' capacity to form hematopoietic colonies in methylcellulose declined with time, whereas they acquired endothelial morphology, expressed endothelial markers, and incorporated into newly forming vascular structures both in vitro and in vivo. Cultured single CD34+ cells formed colonies expressing both hematopoietic (CD45+) and endothelial (CD144+) markers, suggesting they constitute a bona fide hemangioblast population. Conclusion: This system allowed subsequent stages of differentiation of hematopoietic cells to endothelial cells to be defined, underlining the strict interrelationship between endothelial and hematopoietic cells in a hepatocyte environment.

Original languageEnglish
Pages (from-to)1218-1228
Number of pages11
JournalHepatology
Volume45
Issue number5
DOIs
Publication statusPublished - May 2007

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ASJC Scopus subject areas

  • Hepatology

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