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Interaction of Normal and Tumour Haematopoietic Stem Cells with Their Specific Microenvironment (Niche)

This research group is part of Cellular Biology and Virology research program

Research Focus

kostní dřeň_skupina L. Šefc

Stem cells are pluripotent (capable to differentiate into any type of tissue, and adult, which are responsible for a renewal of the particular tissue (hematopoietic neural, intestinal etc.). Recent research has shown that a border between these stem cells makes the expression of just few transcription factors. Stem cell needs an external stimulation to manifest its genetic information. This supplies external microenvironment that communicates with stem cells.  The basic component of extracellular matrix is a niche composed of several stromal accessory cells.  These cells are in direct cell-to-cell communication with a stem cell, and they  secrete cytokines influencing stem cell behaviour. Stem cell needs also other soluble signals including metabolic compounds, oxygen and other gas tension, adhesion to extracellular matrix proteins, as well as neural stimulation.

Our project is based on adult hematopoietic stem cells. These stem cells are used for stem cell transplantations to patients with hematopoietic disorders. The transplanted stem cells should find bone marrow (homing), migrate to available niches (seeding), and start to produce differentiated blood cells (engraftment).

We want to focus mainly to analysis of niche availability for transplanted normal and leukaemic haematopoietic stem/progenitor cells. This can be biased by regeneration of damaged haematopoietic tissue of the host caused by conditioning. We want also to compare murine bone marrow (medullar) and spleen (extramedullar) niches in terms of support, cell composition, and particularly significance of SDF-1 (CXCL12)  cytokine interaction with its receptor CXCR4 for homing and engraftment of transplanted hematopoietic stem cells.

In picture: Bone marrow. Author: Viktor Sýkora 

More info at http://biocev.lf1.cuni.cz

Head of Group

Prof. Emanuel Nečas, M.D., DSc.

_B3E3266
  • Prof. Emanuel Nečas, M.D., DSc.

  • Senior Researcher
  • Interaction of Normal and Tumour-Altered Haematopoietic Stem Cells with Their Specific Microenvironment (Niche)
  • +420 224 965 914
  • The release of bone marrow niches for the transplanted stem cells using ionizing radiation, the kinetics and mechanisms of their occupation by transplanted stem cells in competition with regenerating stem cells of the host.

Most Significant Recent Publications

Hlobeňová T, Šefc L, Chang KT, Savvulidi F, Michalová J, Nečas E.: B-lymphopoiesis gains sensitivity to subsequent inhibition by estrogens during final phase of fetal development. Developmental and Comparative Immunology 2012; 36(2):385-9.

Michalová J, Savvulidi F, Šefc L, Forgáčová K, Nečas E.: Cadaveric bone marrow as potential source of hematopoietic stem cells for transplantation. Chimerism 2011; 2(3):86-87.

Michalová J, Savvulidi F, Šefc L, Faltusová K, Forgáčová K, Nečas EHematopoietic Stem Cells Survive Circulation Arrest and Reconstitute Hematopoiesis in Myeloablated Mice. Biology of  Blood and Marrow Transplantation 2011;17(9):1273-81.

Contacts

1st faculty of Medicine at BIOCEV, Charles University in Prague
Průmyslová 595
252 50 Vestec near Prague
Czech Republic
+420 224 961 111