A new study in Stem Cell Reports this week shows that a biological platform containing immobilised Wnt proteins can act as an artificial stem cell niche by supporting the long-term maintenance of Wnt-responsive stem cells. The platform can also direct cell migration and differentiation in 3D cultures. These findings provide new insights into the conditions required to artificially engineer human tissue.
Wnt signalling pathways are heavily implicated in many aspects of cell biology including cell proliferation, differentiation, migration, cell morphology and apoptosis. It is therefore not surprising that there is great interest in exploiting Wnt proteins for the production of human tissues to repair injury. In living tissues, Wnt proteins are often secreted locally and presented to one side of the responsive cells. While powerful genetic tools can be used to manipulate Wnt signalling, studies of hydrophobic Wnt proteins have been hampered by difficulties with purification and by their localised action. Shukry Habib and his team had previously addressed these difficulties by covalently immobilising biologically active Wnt proteins to microbeads, which mimicked the cellular niche by inducing Wnt signalling pathways in nearby cells. These Wnt signalling pathways affect cell fate decisions in single mammalian stem cells by controlling asymmetric cell division, a process that is essential for tissue formation and regeneration. This approach was an improvement on previous approaches that required Wnt proteins to be dissolved in cytotoxic detergent and thus represented a major breakthrough in the advancement of tools for studying Wnt signalling.
In the current study, Shukry Habib and colleagues devised a one-step immobilisation technique to bind detergent-free Wnt proteins onto commercially available platforms comprising aldehyde surfaces. These Wnt-modified platforms could also be dehydrated and stored for several months without losing biological activity. When Habib’s team seeded cultured stem cells onto these surfaces, they were able to induce Wnt signalling, which enriched and maintained the seeded cultures. When they moved to a 3D culture system whereby an additional dimension was created by adding a layer of gel over seeded human mesenchymal stem cells, they found that the Wnt-modified platform could maintain the stem cell population and direct multilayer formation of mature bone cells. These results are the first to describe in vitro 3D culture conditions where a human stem/progenitor cell population is maintained alongside the formation of differentiated cells in an organized manner.
Although further studies are needed to determine the precise platform specifications required for optimal stem cell division, enrichment and migration, the hope is that these findings will greatly facilitate efforts to produce artificially engineered human tissue.
Shukry Habib states that “Despite major advances in this field, in vitro cell-based assays fail to replicate the complex nature of the 3D microenvironment to effectively model tissues or organs. Furthermore, in vivo results using tissues and cells from commonly used non-primate animals don’t always translate to humans due to cross-species differences. We plan to expand our studies so that they are applicable to other tissues including skin and brain. We are confident that our findings will be pivotal in transforming not just the approaches being developed for human tissue production, but also drug and toxicity testing in these tissues.”
Immobilised Wnt proteins act as a stem cell niche for tissue engineering
Published online: 12th July 2016