Reawakening Atlas: Chemical Approaches To Repair or Replace Dysfunctional Musculature

Abstract

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.

Naturally derived and synthetic scaffolds for skeletal muscle reconstruction

“…Similarly, mice treated with the small molecule 2-acetyl-4(5)-tetrahydroxybutlimidazole (THI), previously shown to increase S1P expression, had a 4-fold increase in the number of cells expressing myf5, a protein that plays a key role in regulating myogenesis and a 3.6-fold increase in the number of muscle cell fibers [168]. Another interesting approach that has been explored is using small molecules to dedifferentiate multinucleated myoblasts into mononuclear proliferatory cells and satellite cells which can then contribute to the regeneration at a different site [169,170]. The use of small molecule therapy for skeletal muscle regeneration has been recently reviewed [171].…”

Small-molecule based musculoskeletal regenerative engineering

“…Although muscles typically regenerate themselves, the regenerative property can become compromised as people age, if they suffer from a muscular degenerative disease (29), or if they experience a large, traumatic injury, in which the natural repair mechanism is unable to cope with the large muscle loss (30). Small molecules can offer an attractive option to satisfy the clinical need for muscle recovery therapeutics (10, 31).…”

“…Interestingly, various groups have demonstrated that the dedifferentiation of myoblasts can be beneficial to muscular regeneration. Under certain conditions, multinucleated myoblasts can dedifferentiate into mononuclear proliferatory cells, satellite cells, which then have potential to differentiate into multinucleated cells at another site (29). Recently, Kim et al .…”

Herzregeneration: Chancen und Aufgaben für die Wirkstoff‐Forschung mit neuartigen chemischen und therapeutischen Methoden oder Agentien

“…[53] [13d, 47,48] Es ist noch viel Arbeit erforderlich, um aufbauend auf diesen Studien Verbindungen -und letztlich klinische Kandidaten -zu identifizieren, die spätere Stadien der Kardiomyozytendifferenzierung adressieren und zu therapeutisch relevanten Kardiomyozytenpopulationen sowie letzten Endes zu einer verbesserten Herzfunktion führen. [54] 2.2. Mikro-RNAs und Anti-Mikro-RNA-Oligonukleotide Mikro-RNAs (miRs) sind kurze (ca.…”