The myelopoietic supportive capacity of mesenchymal stromal cells is uncoupled from multipotency and is influenced by lineage determination and interference with glycosylation.
Cultured bone marrow stromal cells create an in vitro milieu supportive of long-term hemopoiesis and serve as a source for multipotent mesenchymal progenitor cells defined by their ability to differentiate into a variety of mesodermal derivatives. This study aims to examine whether the capacity to support myelopoiesis is coupled with the multipotency. Our results show that the myelopoietic supportive ability of stromal cells, whether from the bone marrow or from embryo origin, is not linked with multipotency; cell populations that possess multipotent capacity may or may not support myelopoiesis, whereas others, lacking multipotency, may possess full myelopoietic supportive ability. However, upon differentiation, the ability of multipotent mesenchymal progenitors to support myelopoiesis is varied. Osteogenic differentiation did not affect myelopoietic supportive capacity, whereas adipogenesis resulted in reduced ability to support the maintenance of myeloid progenitor cells. These differences were accompanied by a divergence in glycosylation patterns, as measured by binding to lectin microarrays; osteogenic differentiation was associated with an increased level of antennarity of N-linked glycans, whereas adipogenic differentiation caused a decrease in antennarity. Inhibition of glycosylation prior to seeding the stroma with bone marrow cells resulted in reduced capacity of the stromal cells to support the formation of cobblestone areas. Our data show that myelopoietic support is unrelated to the multipotent phenotype of cultured mesenchymal progenitors but is dependent on the choice of differentiation pathway and upon correct glycosylation of the stromal cells.
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Vered
V
Morad
Meirav
M
Pevsner-Fischer
Sivan
S
Barnees
Albena
A
Samokovlisky
Liat
L
Rousso-Noori
Rakefet
R
Rosenfeld
Dov
D
Zipori
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D006031:Glycosylation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D039902:Multipotent Stem Cells / Q000166:cytology*; D038042:Myelopoiesis; D017154:Stromal Cells / Q000166:cytology