Locally controlled release of immunosuppressive promotes survival of transplanted adult spinal cord tissue

Abstract

Transplantation of adult spinal cord tissue (aSCT) is a promising treatment for spinal cord injury (SCI) basing on various types of neural cells and matrix components inside aSCT. However, long-term systemic administration of immunosuppressors (e.g. tacrolimus, TAC) is required for the survival of allogeneic tissue, which often associated with severe side effects such as infection, liver damage, and renal failure, etc. In this study, a triglycerol monostearate-based (TGM) TAC delivery system (e.g. TAC@TGM) with high drug loading concentration was developed, which possessed injectable properties as well as sustainable and immune-responsive drug release behaviors. In complete transected SCI model, locally injected TAC@TGM could reduce the infiltration of inflammation cells, enhance the survival of transplanted aSCT (e.g. Tuj-1+ and NF+ neurons), and promote the recovery of locomotor function. Moreover, controlled release of TAC by TAC@TGM attenuated side effects of TAC on liver and kidneys compared with traditional systemic administration. More importantly, the developed TAC@TGM system provided a facile single dose of long-term immunosuppressive effect not just for aSCT transplantation, but also for other tissue/organ and cell transplantations. Graphical abstract

Sustained delivery of NT-3 and curcumin augments microenvironment modulation effects of decellularized spinal cord matrix hydrogel for spinal cord injury repair

“…It was widely acknowledged that SCI triggers innate inflammatory events with immediate infiltration of inflammatory cells into the lesion site, which further forms a harsh microenvironment and hinders nerve regeneration. Therefore, controlled regulation of inflammatory responses in the early stage has been a valid therapeutic approach [ 49 ], in which case, the phenotype modulation of microglia and macrophages becomes critical in treatments of SCI [ 50 ]. In this study, a general biomarker CD68 was used for identification of macrophages/microglia, co-stained with biomarker CD206 for their anti-inflammatory phenotypes to assess different subpopulation of the activated macrophage/microglia at the lesion sites of all groups 2 weeks after contused SCI ( Figure 8A–C ).…”