Hydrogel could simplify regenerative medicine

A new stem cell microenvironment created by researchers at the University of Nottingham allows the self-renewal of cells and then their evolution into heart cells. The two distinct phases require different material environments and until now, a single substance that does both jobs has not been available. The new hydrogel contains two polymers – an alginate-rich environment to allow proliferation and self-renewal, and a collagen-rich environment for differentiation. The material uses ionic de-cross-linking to remove the alginate material and switch to the collagen material when the cell population is big enough. This change then triggers the next stage of growth when cells develop their specific purpose. “Our new combination of hydrogels is a first,” said Kevin Shakesheff, Professor of Advanced Drug Delivery and Tissue Engineering. “It allows dense tissue structures to be produced from human pluripotent stem cells (HPSC) in a single step process never achieved before.” “Both alginate and collagen are well used hydrogels in the field of tissue engineering,” research fellow James E Dixon told Laboratory News. “Alginate is known not to really interact with cells and it very easily changes from a liquid to a gel and back again by treating it with non-toxic chemicals. Collagen interacts well with cells and needs a chemical change to make fibres which cells attach to. Using the properties of a cell non-sticky verses sticky gel and changing this property we were able to control the stem cell behaviour.” Adjusting the timing of the switch can promote specific lineage differentiation as in vivo the researchers write in their PNAS paper. They showed that directing early lineage specification using this single system can promote cardiogenesis with increased gene expression in high-density cell populations. “The change in the cell stickiness (and other properties) when we chemically treat the cells in our hydrogels tells the cells to stop being stem cells and to move forward and differentiate into other cell/tissue types,” Dixon said. “To help these cells decide to become cardiomyocytes we gave them additional instructions in the form of growth factors which are involved in this process during pregnancy or we genetically tricked the cells to become heart cells by turning on genes that are involved in making the heart during pregnancy.” “The discovery has important implications for the future of manufacturing in regenerative medicine,” said Shakesheff. “This field of healthcare of a major priority for the UK and we are seeing increasing investment in future manufacturing processes to ensure we are ready to deliver real treatments to patients when HPSC products and treatments go to trial and become standard.” Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation