Abstract

Surprisingly little is known regarding the effects of the physical microenvironmental niche on haemopoietic stem cells. We have explored the effects of matrix elasticity on stem cell properties using a unique synthetic substrate, tropoelastin, which we used to show that both murine and human primitive haemopoietic cells are more efficiently maintained on an elastically extensible substrate than controls. We have shown that culturing primitive murine and human cord blood haemopoietic cells on tropoelastin in vitro led to increases in cell number, clonogenicity, proliferation and engraftment following transplantation. Atomic force measurements of truncations and crosslinked tropoelastin strengthen the hypothesis that stem cells sense the elasticity of their microenvironment. A consequence of this idea is that alterations to niche elasticity in disease states may contribute to abnormal haemopoiesis. Further, elastic substrates such as tropoelastin may offer a new approach to biomaterial design aimed to achieve optimal ex vivo culture conditions for primitive haemopoietic cells. In order to take advantage of this type of observation arising from the basic research laboratory (and many other opportunities in cellular therapies), a basic introduction in the principles and regulatory aspects of good manufacturing practice of cellular therapeutics will be provided.

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