Crosstalk between Murine Liver Sinusoidal Endothelial Cells (LSEC) and Hematopoietic Stem Cells during In Vitro Hematopoiesis.

Abstract

Crosstalk between murine liver sinusoidal endothelial cells (LSEC) and hematopoietic stem cells during in vitro hematopoiesis. G. Luna, J. E. Cardier. Laboratorio de Patologia Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC). Apartado 21827, Caracas, VenezuelaWe have showed that at the liver there is a specific hematopoietic microenvironment, constituted by the liver sinusoid endothelial cells (LSEC), which are capable to support, in vitro and in vivo, not only the proliferation but also the differentiation and survival of hematopoietic stem cells (HSC). The ability of LSEC to support hematopoiesis could be related to specific hematopoietic molecules expressed by these cells. In this study, we investigate the expression of some cell adhesion molecules (VCAM-1, ICAM-1, and the integrin a4b1 ), and early acting hematopoietic cytokines (IL-6 and GM-CSF), on LSEC cocultured with HSC. The expression of VCAM-1, ICAM-1, α4β1, IL6 and GM-SCF was increased on LSEC cocultured with HSC. In contrast, a significant decrease in the expression of IL-6 and GM-CSF in the HSC derived from the same cocultures was observed. The blockade of VCAM-1 on LSEC reduced significantly the adhesion of HSC to LSEC monolayers, suggesting that this molecule is involved in the binding of HSC to LSEC microenvironments. There were not changes in the expression of the molecules evaluated when the LSEC and HSC were co-cultured in non-contact conditions, suggesting that soluble factors do not participate in regulating the expression of these molecules. Our data shows that during in vitro hematopoiesis, LSEC are activated to express molecules associated with the hematopoiesis process. LSEC activation is regulated by the contact between these cells and HSC. By expressing critical hematopoietic microenvironment molecules, LSEC may regulate the proliferation and differentiation of HSC, during liver extramedullary hematopoiesis.