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Background The multipotency of adipose-derived mesenchymal stem cells (ADMSC) could be an advantage to regenerate tissues with multiple cell types. However, due to the hostile nature, trauma sites like spinal cord injury can augment the ADMSC differentiation into undesirable lineages. Immersing pre-differentiated neural progenitors in a biomimetic niche during delivery could guard them against any undesired differentiation or death. Objective The study proposes using an insoluble cell-specific fibrin niche for in vitro differentiation of rat ADMSCs to neural progenitor cells (NPCs) and oligodendrocyte progenitor cells (OPCs). Further, the study explores fibrin hydrogel for in vivo progenitor cell delivery, and that can aid post-transplant survival/differentiation. Design The in vitro experiments analyzed for differentiation-specific markers to establish derivation of rADMSCs to rNPCs and rOPCs. The derived progenitors, tagged with fluorescent tracker dye were delivered in rat T10 contusion SCI using fibrin hydrogel. After 28 days, imaged the experiment site to determine cell survival, immunostained the tissues to identify differentiation of transplanted cells, and evaluated the effect of fibrin and cells on regulating the injury-associated immune response. Results The study demonstrated fibrin niche aided stable differentiation of rat ADMSCs into neural progenitors. Fibrin matrix holds up the delivered progenitor cells in the SCI site. The H&E stained tissues revealed regulated cavitation, astrogliosis, and inflammation in test tissues. Progression of transplanted cells into oligodendrocytes upon delivering a mixture of rNPCs, rOPCs, and fibrin is evident …