Wnt signaling activation: targets and therapeutic opportunities for stem cell therapy and regenerative medicine.
RSC Chem Biol
This review article talks about the use of small molecules that target specific proteins from a signaling pathway present in the stem cells called Wnt signaling pathway with the aim of using them to treat limbal stem cell deficiency.
Wnt proteins are secreted morphogens that play critical roles in embryonic development, stem cell proliferation, self-renewal, tissue regeneration and remodeling in adults. While aberrant Wnt signaling contributes to diseases such as cancer, activation of Wnt/beta-catenin signaling is a target of interest in stem cell therapy and regenerative medicine. Recent high throughput screenings from chemical and biological libraries, combined with improved gene expression reporter assays of Wnt/beta-catenin activation together with rational drug design, led to the development of a myriad of Wnt activators, with different mechanisms of actions. Among them, Wnt mimics, antibodies targeting Wnt inhibitors, glycogen-synthase-3beta inhibitors, and indirubins and other natural product derivatives are emerging modalities to treat bone, neurodegenerative, eye, and metabolic disorders, as well as prevent ageing. Nevertheless, the creation of Wnt-based therapies has been hampered by challenges in developing potent and selective Wnt activators without off-target effects, such as oncogenesis. On the other hand, to avoid these risks, their use to promote ex vivo expansion during tissue engineering is a promising application.