Combined Administration of ASCs and BMP-12 Promotes an M2 Macrophage Phenotype and Enhances Tendon Healing

摘要: Outcomes after intrasynovial tendon repair are highly variable. An intense inflammatory cascade followed by a delayed healing response can cause adhesion formation and repair-site failure that severely impair the function of repaired digits. No effective remedies exist to fully address these issues. Cell- growth factor-based therapies have been shown modulate inflammation improve cell proliferation matrix synthesis therefore promising treatment approaches for repair. (1) Can autologous adipose-derived mesenchymal stromal cells (ASCs) recombinant bone morphogenetic protein-12 (rBMP-12) be effectively delivered an flexor without adverse effects? (2) Do ASCs injury repair? (3) Does combined application rBMP-12 proliferative remodeling responses Sixteen 1- 2-year-old female canines were used in this study. Autologous ASC sheets, with rBMP-12, applied surface sutured tendons. Fourteen days repair, effects determined using quantitative PCR (six per group) expression genes related macrophage phenotype or (IL-4, CD163, VEGF, NOS2, IL-1B, IFNG), (CCND1), (SCX, TNMD, COL1A1 COL3A1). Proteomics analysis (four was performed examine changes protein abundances. CD146 immunostaining hematoxylin eosin staining detect stem progenitor semiquantitatively evaluate cellularity at repair; analyses done blinded group. Gross inspection tracing showed site deleterious gap formation. Quantitative assessment gene treatment: ASC-sheet modulated postrepair facilitated increasing regenerative M2 macrophages (M2 marker CD204, twofold normal, p = 0.030), inhibitor (prostaglandin reductase 1 [PTRG1], 1.6-fold 0.026), proteins involved (periostin [POSTN], 1.9-fold 0.035). Consistently, semiquantitative qualitative evaluations tissue reduced mononuclear infiltration (12% less than nontreated tendons, 0.021) introduced CD146+ site. The administration further stimulated IL-4 (116-fold 0.002) led increase effector metalloproteinase-12 (twofold 0.016) reduction negative regulator angiogenesis migration (StAR-related lipid transfer domain protein13 [STARD13]; 84% 0.000), thus facilitating stage BMP-12 accelerated progression on functional recovery should evaluated future studies. sheet approach is effective, biocompatible, surgeon-friendly factor delivery during Combined may accelerate while suppressing response.