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New porous hydrogel could boost success of stem-cell-based tissue regeneration.

Stem cell therapies are often limited by low survival of transplanted stem cells and the lack of precise control over their differentiation into the terminal cell types needed to repair or replace injured tissues. Now, a team led by Wyss Institute Core Faculty member David Mooney, Ph.D., has developed a new strategy — embedding stem cells into porous, transplantable hydrogels — that has experimentally improved bone repair by boosting the survival rate of transplanted stem cells and influencing their cell differentiation.

Stem cell therapies bear tremendous hopes for the repair of many tissues and bone or even the replacement of entire organs. Tissue-specific stem cells can now be generated in the laboratory. However, no matter how well they grow in the laboratory, stem cells must survive after they are transplanted and function correctly at the site of injury to be useful for clinical regenerative therapies. As of now, transplanted cell death remains a major challenge.

To improve the therapeutic ability of transplanted stem cells, Mooney’s team has drawn inspiration from naturally occurring stem cell “niches. ” A ‘stem cell niche’ is a unique support system for stem cells consisting of other cell types and an extracellular molecular matrix that affects their fate.

Recently, Mooney’s team as well as other researchers have identified specific chemical and physical cues from the niche that act in concert to promote stem cell survival, multiplication and maturation into tissue. Whereas chemical signals that control stem cell behaviour are increasingly understood, much less is known about the mechanical properties of stem cell niches. Stem cells like those present in bone, cartilage or muscle cultured in laboratories, however, have been found to possess mechanosensitivities; meaning they require a physical substrate with defined elasticity and stiffness to proliferate and mature on.

“This study provides the first demonstration that the physical properties of a biomaterial can not only help deliver stem cells but also tune their behaviour in vivo,” said Mooney. “While so far we have focused on orchestrating bone formation, we believe that our hydrogel concept can be broadly applied to other regenerative processes as well.”

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