Reawakening atlas: chemical approaches to repair or replace dysfunctional musculature

Muscle diseases are major health concerns. For example, ischemic heart disease is the third most common cause of death. Cell therapy is an attractive approach for treating muscle diseases, although this is hampered by the need to generate large numbers of functional muscle cells. Small molecules have become established as attractive tools for modulating cell behavior and, in this review, we discuss the recent, rapid research advances made in the development of small molecule methods to facilitate the production of functional cardiac, skeletal, and smooth muscle cells. We also describe how new developments in small molecule strategies for muscle disease aim to induce repair and remodelling of the damaged tissues in situ. Recent progress has been made in developing small molecule cocktails that induce skeletal muscle regeneration, and these are discussed in a broader context, because a similar phenomenon occurs in the early stages of salamander appendage regeneration. Although formidable technical hurdles still remain, these new advances in small molecule-based methodologies should provide hope that cell therapies for patients suffering from muscle disease can be developed in the near future.