Alginate hydrogel encapsulated MDSC cell spheroids delivery as a regenerative therapy to muscle injury in vivo

Abstract

Being the most abundant tissue in the human body, skeletal muscle is subject to several conditions that are relatively common in the medical field, such as lacerations and bruises, resulting from trauma, ischemia, resulting from vascular insufficiency, and neurological dysfunction, which can be secondary to the trauma itself or associated diseases. The various disorders caused by these mechanisms affect the muscle, significantly impacting the maintenance of quality-adjusted life years (QALYs), relating to a higher incidence of recurrent muscle diseases. In the meantime, it is known that the muscle is one of the organs with the greatest regeneration capacity. This fact is due to a pool of satellite cells, with different characteristics and lineages, destined to the process of differentiation and repair of injured muscle fibers. Among this set of cells, the lineage entitled muscle-derived stem-like cells (MDSC) exhibits an excellent ability to differentiate into myoblastic lineages, as well as endothelial and neuronal lineages, in the setting of appropriate stimuli. This is due to a partial state of reprogrammed pluripotency inherent to the constituents of the genetic heritage of this lineage. Given the frequent epidemiology of muscle injury and its impact on quality of life, the present project explores the possibility of creating a therapeutic flap model from three-dimensional cell coculture of MDSC spheroids, differentiated into myoblastic and endothelial lineages, and then encapsulated with alginate hydrogel, creating a favorable microenvironment for cellular interaction with the extracellular matrix, to then be delivered to the injured murine muscle with volumetric muscle loss, for evaluating its regenerative potential.