Stem Cell Transplantation for Muscular Dystrophy: The Challenge of Immune Response
Figure 1
Dynamics of inflammation and muscle regeneration in acute and chronic injury. Acute muscle injury (a) triggers local release of chemoattractants that induce PMNs and M1 invasion into the damaged tissue. PMNs and M1 release an array of molecules (such as NO) that further amplify local inflammation, contributing to debris clearance and SC activation. This initial Th1-driven inflammation is later overcome by an anti-inflammatory response that coincides with a M1-to-M2 switch. By day 4 Tregs reach the site of injury, modulating Tconv expansion and activation and SC differentiation through amphiregulin release. M2 and Th2 cytokines reduce local inflammation and contribute to SCs differentiation, thus promoting the latest stages of muscle regeneration. Upon damage repair, SCs return to quiescence. Chronic muscle injuries (b) are characterised by persistent inflammation. Muscles feature infiltrates of PMNs, M1 together with M2, Tconv, and Treg; moreover, the simultaneous release of pro- and anti-inflammatory molecules promotes incomplete tissue regeneration and fibrosis. The SC pool undergoes depletion due to continuous rounds of activation and differentiation, resulting in terminal muscle wasting. SC: satellite cells; PMN: neutrophils; M1: M1 macrophages; M2: M2 macrophages; Tconv: CD4+ conventional T cell; Tregs: CD4+ Foxp3+ regulatory T cell; NO: nitric oxide; Red box: Th1-driven response; Green box; Th2-driven response.
