Decellularized Brain Matrix Enhances Macrophage Polarization and Functional Improvements in Rat Spinal Cord Injury
- Decellularized Brain Matrix Enhances Macrophage Polarization and Functional Improvements in Rat Spinal Cord Injury
- 김수현; 서유진; 홍진영; Ganchimeg Davaa; 김해원; 현정근
- Issue Date
- Acta Biomaterialia
- VOL 101-371
- Spinal cord injury (SCI) is a devastating lesion lacking effective treatment options currently available in clinics. The inflammatory process exacerbates the extent of the lesion through a secondary injury mechanism, where proinflammatory classically activated macrophages (M1) are prevalent at the lesion site. However, the polarized alternatively activated anti-inflammatory macrophages (M2) are known to play an important role in wound healing and regeneration following SCI. Herein, we introduce porcine brain decellularized extracellular matrix (dECM) to modulate the macrophages in the injured spinal cord. The hydrogels with collagen and dECM at various dECM concentrations (1, 5, and 8？mg/ml) were used to cultivate primary macrophages and neurons. The dECM hydrogels were shown to promote the polarization of macrophages toward M2 phase and the neurite outgrowth of cortical and hippocampal neurons. When the dECM hydrogels were applied to rat SCI models, the proportion of M1 and M2 macrophages in the injured spinal cord was substantially altered. When received dECM concetration of 5？mg/ml, the expression of molecules associated with M2 (CD206, arginase1, and IL-10) was significantly increased. Consistently, the population of total macrophages and cavity area were substantially reduced in the dECM-treated groups. As a result, the locomotor functions of injured spinal cord, as assessed by BBB and ladder scoring, were significantly improved. Collectively, the porcine brain dECM with optimal concentration promotes functional recovery in SCI models through the activation of M2 macrophages, suggesting the promising use of the engineered hydrogels in the treatment of acute SCI.
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