In Silico and In Vivo Experiments Reveal M-CSF Injections Accelerate Regeneration Following Muscle Laceration
Authored by Kyle S Martin, Silvia S Blemker, Shayn M Peirce, Kelley M Virgilio, Christopher D Kegelman, Julianna A Passipieri, George J Christ
Date Published: 2017
DOI: 10.1007/s10439-016-1707-2
Sponsors:
United States National Science Foundation (NSF)
Platforms:
NetLogo
Model Documentation:
Other Narrative
Flow charts
Model Code URLs:
https://simtk.org/projects/regenerationabm
Abstract
Numerous studies have pharmacologically modulated the muscle milieu in
the hopes of promoting muscle regeneration; however, the timing and
duration of these interventions are difficult to determine. This study
utilized a combination of in silico and in vivo experiments to
investigate how inflammation manipulation improves muscle recovery
following injury. First, we measured macrophage populations following
laceration injury in the rat tibialis anterior (TA). Then we calibrated
an agent-based model (ABM) of muscle injury to mimic the observed
inflammation profiles. The calibrated ABM was used to simulate
macrophage and satellite stem cell (SC) dynamics, and suggested that
delivering macrophage colony stimulating factor (M-CSF) prior to injury
would promote SC-mediated injury recovery. Next, we performed an
experiment wherein 1 day prior to injury, we injected M-CSF into the rat
TA muscle. M-CSF increased the number of macrophages during the first 4
days post-injury. Furthermore, treated muscles experienced a swifter
increase in the appearance of PAX7(+) SCs and regenerating muscle
fibers. Our study suggests that computational models of muscle injury
provide novel insights into cellular dynamics during regeneration, and
further, that pharmacologically altering inflammation dynamics prior to
injury can accelerate the muscle regeneration process.
Tags
Agent-based model
inflammation
Macrophages
Force transmission
Apoptotic cells
Tgf-beta
Injury
Muscle regeneration
Computational
model
Regenerative pharmacology
Satellite stem cells
Growth-factor-i
Mouse skeletal-muscle
Satellite cells
Macrophage
phenotype
Tendon transfer
Factor-beta