Bone marrow mobilization & local SDF-1α delivery enhances nascent supraspinatus muscle fiber growth.

Rotator cuff tear is a significant problem that leads to poor clinical outcomes due to muscle degeneration after injury. The objective of this study was to synergistically increase the number of pro-regenerative cells recruited to injured rotator cuff muscle through a novel dual treatment system, consisting of a bone marrow mobilizing agent (VPC01091), hypothesized to "push" pro-healing cells into the blood, and localized delivery of Stromal cell-derived factor 1α (SDF-1α), to "pull" the cells to the injury site. Immediately after rotator cuff tendon injury in rat, the mobilizing agent was delivered systemically, and SDF-1α-loaded heparin based microparticles were injected into the supraspinatus muscle. Regenerative and degenerative changes to supraspinatus muscle, and the presence of inflammatory/immune cells, mesenchymal stem cells, and satellite cells, were assessed via flow cytometry and histology for up to 21 days. After dual treatment, significantly more mesenchymal stem cells (31.9 ± 8.0% single cells) and T lymphocytes (6.7 ± 4.3 per 20X field of view) were observed in supraspinatus muscle 7 days after injury and treatment compared to Injury alone (14.4 ± 6.5% single cells, 1.2 ± 0.7 per 20X field of view), in addition to an elevated M2:M1 macrophage ratio (3.0 ± 0.5), an indicator of a pro-regenerative environment. These pro-regenerative cellular changes were accompanied by increased nascent fiber formation (indicated by embryonic myosin heavy chain staining) at day 7 compared to SDF-1α treatment alone, suggesting that this method may be a promising strategy to influence the early cellular response in muscle and promote a pro-regenerative micro-environment to increase muscle healing after severe rotator cuff tear.