Mammalian Blastema: Possibility and Potentials

Regeneration is a process that restores the structure and function of injured tissues or organs. Regenerative capacities vary significantly across species, with amphibians and fish demonstrating a high regenerative capacity even after severe injuries. This capacity is largely attributed to the formation of a blastema, a mass of multipotent cells reprogrammed from differentiated cells at the injury site. In contrast, mammals exhibit limited regenerative capacities, with blastema- like cells forming only in specific contexts, such as antler or digit tip regeneration. An interesting aspect of blastema formation in highly regenerative organisms is the temporary expression of pluripotency factors as known as the Yamanaka factors (YFs), which is a key requirement for reprogramming somatic cells into induced pluripotent stem cells (iPSCs). While iPSCs hold pros and cons, direct or partial reprogramming with YF has been proposed as a safer alternative. Since blastema formation and partial reprogramming are similar in terms of YF expressions, we found blastema-like cells in mammalian reprogramming with YF. This review outlines the characteristics of blastema across various organisms, emphasizing interspecies differences. We also explore studies on partial reprogramming and the possibility of inducing blastema-like cells via the temporary expression of YF in mammals.