title: Substrate elasticity provides mechanical signals for the expansion of hemopoietic stem and progenitor cells.
abstract: 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.
authors.affiliation: Gene & Stem Cell Therapy Program, Centenary Institute, Camperdown, New South Wales, Australia.
authors.forename: Jeff
authors.initials: J
authors.lastname: Holst
authors.forename: Sarah
authors.initials: S
authors.lastname: Watson
authors.forename: Megan S
authors.initials: MS
authors.lastname: Lord
authors.forename: Steven S
authors.initials: SS
authors.lastname: Eamegdool
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Bax
authors.forename: Lisa B
authors.initials: LB
authors.lastname: Nivison-Smith
authors.forename: Alexey
authors.initials: A
authors.lastname: Kondyurin
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.forename: Andres F
authors.initials: AF
authors.lastname: Oberhauser
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Weiss
authors.forename: John E J
authors.initials: JE
authors.lastname: Rasko
mesh_terms: 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
chemical_list: D003432:Cross-Linking Reagents; D005353:Fibronectins; D050505:Mutant Proteins; D014333:Tropoelastin; D003094:Collagen