tud
eng
Hematopoietic stem cells in co-culture with mesenchymal stromal cells - modeling the niche compartments in vitro
2010
urn:nbn:de:bsz:14-qucosa-177403
born digital
aut
Dr.
Rainer
Ordemann
aut
Duohui
Jing
aut
Ana-Violeta
Fonseca
aut
Nael
Alakel
aut
Fernando A.
Fierro
aut
Katrin
Muller
aut
Martin
Bornhauser
aut
Gerhard
Ehninger
aut
Denis
Corbeil
pbl
Ferrata Storti Foundation
Ferrata Storti Foundation, Pavia
Background
Hematopoietic stem cells located in the bone marrow interact with a specific microenvironment referred to as the stem cell niche. Data derived from ex vivo co-culture systems using mesenchymal stromal cells as a feeder cell layer suggest that cell-to-cell contact has a significant impact on the expansion, migratory potential and ‘stemness’ of hematopoietic stem cells. Here we investigated in detail the spatial relationship between hematopoietic stem cells and mesenchymal stromal cells during ex vivo expansion.
Design and Methods
In the co-culture system, we defined three distinct localizations of hematopoietic stem cells relative to the mesenchymal stromal cell layer: (i) those in supernatant (non-adherent cells); (ii) those adhering to the surface of mesenchymal stromal cells (phase-bright cells) and (iii) those beneath the mesenchymal stromal cells (phase-dim cells). Cell cycle, proliferation, cell division and immunophenotype of these three cell fractions were evaluated from day 1 to 7.
Results
Phase-bright cells contained the highest proportion of cycling progenitors during co-culture. In contrast, phase-dim cells divided much more slowly and retained a more immature phenotype compared to the other cell fractions. The phase-dim compartment was soon enriched for CD34+/CD38− cells. Migration beneath the mesenchymal stromal cell layer could be hampered by inhibiting integrin β1 or CXCR4.
Conclusions
Our data suggest that the mesenchymal stromal cell surface is the predominant site of proliferation of hematopoietic stem cells, whereas the compartment beneath the mesenchymal stromal cell layer seems to mimic the stem cell niche for more immature cells. The SDF-1/CXCR4 interaction and integrin-mediated cell adhesion play important roles in the distribution of hematopoietic stem cells in the co-culture system.
Biotechnologie, hämatopoetische Stammzellen
hematopoietic stem cells, CXCR4, integrin β1, biotechnology
610
XA 10000
1592-8721
2016-01-04
456899731
Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden
4519974-7
prv
Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, Dresden
10.3324/haematol.2009.010736
Link zur Originalpublikation in der Zeitschrift Haematologica.
http://dx.doi.org/10.3324/haematol.2009.010736
Haematologica. 2010 Apr; 95(4) S.542–550, ISSN 1592-8721
Krause
baerbel.krause@slub-dresden.de
article
TUD-20-1664