Open AccessLong‐Term Maintenance of Hematopoietic Stem Cells Does Not Require Contact with Embryo‐Derived Stromal Cells in Cocultures
Author(s) -
Oostendorp Robert A.J.,
Robin Catherine,
Steinhoff Christine,
Marz Stefanie,
Bräuer Rosalinde,
Nuber Ulrike A.,
Dzierzak Elaine A.,
Peschel Christian
Publication year - 2005
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2004-0120
Subject(s) - biology , stromal cell , stem cell , haematopoiesis , bone marrow , microbiology and biotechnology , stem cell factor , immunology , embryonic stem cell , growth factor , cancer research , genetics , gene , receptor
We recently established that two midgestation‐derived stromal clones—UG26‐1B6, urogenital ridge–derived, and EL08‐1D2, embryonic liver–derived—support the maintenance of murine adult bone marrow and human cord blood hematopoietic repopulating stem cells (HSCs). In this study, we investigate whether direct HSC‐stroma contact is required for this stem cell maintenance. Adult bone marrow ckit + Ly‐6C − side population (K6‐SP) cells and stromal cells were cocultured under contact or noncontact conditions. These experiments showed that HSCs were maintained for at least 4 weeks in culture and that direct contact between HSCs and stromal cells was not required. To find out which factors might be involved in HSC maintenance, we compared the gene expression profile of EL08‐1D2 and UG26‐1B6 with four HSC‐nonsupportive clones. We found that EL08‐1D2 and UG26‐1B6 both expressed 21 genes at a higher level, including the putative secreted factors fibroblast growth factor‐7, insulin‐like growth factor‐binding proteins 3 and 4, pleiotrophin, pentaxin‐related, and thrombospondin 2, whereas 11 genes, including GPX‐3 and HSP27 , were expressed at a lower level. In summary, we show for the first time long‐term maintenance of adult bone marrow HSCs in stroma noncontact cultures and identify some secreted molecules that may be involved in this support.