Muse cells: ushering in a new era of stem cell-based therapy for stroke

Stem cell-based regenerative therapies have recently become promising and advanced for treating stroke. Mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs) have received the most attention for treating stroke because of the outstanding paracrine function of MSCs and the three-germ-layer differentiation ability of iPSCs. However, the unsatisfactory homing ability, differentiation, integration, and survival time in vivo limit the effectiveness of MSCs in regenerative medicine. The inherent tumorigenic property of iPSCs renders complete differentiation necessary before transplantation, which is complicated and expensive and affects the consistency among cell batches. Multilineage differentiating stress-enduring (Muse) cells are natural pluripotent stem cells in the connective tissues of nearly every organ and thus are considered nontumorigenic. A single Muse cell can differentiate into all three-germ-layer, preferentially migrate to damaged sites after transplantation, survive in hostile environments, and spontaneously differentiate into tissue-compatible cells, all of which can compensate for the shortcomings of MSCs and iPSCs. This review summarizes the recent progress in understanding the biological properties of Muse cells and highlights the differences between Muse cells and other types of stem cells. Finally, we summarized the current research progress on the application of Muse cells on stroke and challenges from bench to bedside.