Effect of biodegradable fibrin scaffold on survival, migration, and differentiation of transplanted bone marrow stromal cells after cortical injury in rats

Abstract

In this study the authors' aim was to assess whether fibrin matrix could act as an injectable, valuable scaffold in bone marrow stromal cell (BMSC) transplantation for injured CNS tissue. Both clotting time and 3D structure of fibrin matrix were analyzed with various concentrations of fibrinogen and CaCl(2). The BMSCs were harvested from green fluorescent protein-transgenic mice and cultured. A cortical lesion was produced in rats by application of a very cold rod to the right cerebral hemisphere. The BMSCs, fibrin matrix, or BMSC-fibrin matrix complex was transplanted into the lesion though a small bur hole 7 days after the insult. Using immunohistochemical analysis, the authors evaluated the survival, migration, and differentiation of the transplanted cells 4 weeks after transplantation. Based on in vitro observations, the concentrations of fibrinogen and CaCl(2) were fixed at 2.5 mg/ml and 2 microM in animal experiments, respectively. Fibrin matrix almost completely disappeared 4 weeks after transplantation. However, immunohistochemical analysis revealed that fibrin matrix exclusively enhanced the retention of the transplanted cells within the lesion, migration toward the lesion boundary zone, and differentiation into the neurons and perivascular cells. Injectable fibrin matrix enhanced the survival, migration, and differentiation of the BMSCs transplanted into the cortical lesion in rats. The authors believe that it is one of the promising candidates for a potential, minimally invasive scaffold for CNS disorders. The present findings strongly suggest that such a strategy of tissue engineering could be a therapeutic option for CNS regeneration in patients with CNS injuries.