Substrate elasticity provides mechanical signals for the expansion of hemopoietic stem and progenitor cells.
Surprisingly little is known about the effects of the physical microenvironment on hemopoietic stem and progenitor cells. To explore the physical effects of matrix elasticity on well-characterized primitive hemopoietic cells, we made use of a uniquely elastic biomaterial, tropoelastin. Culturing mouse or human hemopoietic cells on a tropoelastin substrate led to a two- to threefold expansion of undifferentiated cells, including progenitors and mouse stem cells. Treatment with cytokines in the presence of tropoelastin had an additive effect on this expansion. These biological effects required substrate elasticity, as neither truncated nor cross-linked tropoelastin reproduced the phenomenon, and inhibition of mechanotransduction abrogated the effects. Our data suggest that substrate elasticity and tensegrity are important mechanisms influencing hemopoietic stem and progenitor cell subsets and could be exploited to facilitate cell culture.
Holst
Jeff
J
Gene & Stem Cell Therapy Program, Centenary Institute, Camperdown, New South Wales, Australia.
Watson
Sarah
S
Lord
Megan S
MS
Eamegdool
Steven S
SS
Bax
Daniel V
DV
Nivison-Smith
Lisa B
LB
Kondyurin
Alexey
A
Ma
Liang
L
Oberhauser
Andres F
AF
Weiss
Anthony S
AS
Rasko
John E J
JE
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000378:metabolism; D004548:Elasticity / Q000187:drug effects; D005312:Fetal Blood / Q000166:cytology; D005353:Fibronectins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D050505:Mutant Proteins / Q000378:metabolism; D058525:Quartz Crystal Microbalance Techniques; D015398:Signal Transduction / Q000187:drug effects; D013379:Substrate Specificity / Q000187:drug effects; D014333:Tropoelastin / Q000378:metabolism / Q000494:pharmacology
D003432:Cross-Linking Reagents; D005353:Fibronectins; D050505:Mutant Proteins; D014333:Tropoelastin; D003094:Collagen