Substrate elasticity provides mechanical signals for the expansion of hemopoietic stem and progenitor cells

• Published in: Nature biotechnology 2010-10, Vol.28 (10), p.1123-1128
• Main Authors: Rasko, John E J, Holst, Jeff, Watson, Sarah, Lord, Megan S, Eamegdool, Steven S, Bax, Daniel V, Nivison-Smith, Lisa B, Kondyurin, Alexey, Ma, Liang, Oberhauser, Andres F, Weiss, Anthony S
• Format: Article
• Language: English
• Subjects: 631/1647/1407/651; 631/532/1542; 631/61/54; Agriculture; Animal cells; Animals; Bioinformatics; Biological and medical sciences; Biological effects; Biomaterials; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedical materials; Biomedicine; Biotechnology; Cell culture; Cell Proliferation - drug effects; Collagen - metabolism; Cross-Linking Reagents - metabolism; Cytokines; Elasticity - drug effects; Establishment of new cell lines, improvement of cultural methods, mass cultures; Eukaryotic cell cultures; Fetal Blood - cytology; Fibronectins - metabolism; Fundamental and applied biological sciences. Psychology; Genetic aspects; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - metabolism; Humans; letter; Life Sciences; Methods. Procedures. Technologies; Mice; Mice, Inbred C57BL; Mutant Proteins - metabolism; Physiological aspects; Quartz Crystal Microbalance Techniques; Signal Transduction - drug effects; Stem cells; Substrate Specificity - drug effects; Substrates; Tropoelastin - metabolism; Tropoelastin - pharmacology
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt.1687

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.