Very recently, we evaluated the utility of a fibrin matrix as a biodegradable scaffold in cell transplantation for a hemisected spinal cord in rats. The results showed that the animals treated with the BMSC-fibrin matrix construct showed significantly more pronounced recovery of neurologic function than vehicle- or BMSC-treated animals. Histological analysis revealed that the fibrin scaffold markedly improved the survival and migration of the transplanted cells [2].

However, these techniques of tissue engineering for CNS disorders are based on the direct injection of donor cells and biomaterial into the injured CNS tissue. Such techniques may provoke additional CNS injury. In the present study, therefore, we aimed to develop a noninvasive tissue-engineering technique for CNS disorders; we found that the implantation of the BMSC-TGP construct onto the intact neocortical surface promoted the survival, migration, and differentiation of BMSCs in our animal cerebral infarct model. The BMSCs migrated extensively into the peri-infarct neocortex, hippocampus, corpus callosum, and contralateral neocortex, and the majority of them morphologically simulated neurons and expressed neuronal markers.

This is the first report that denotes the utility of a noninvasive tissue-engineering procedure for CNS disorders. This study clearly showed that BMSCs could penetrate through the pia mater of the intact neocortex and migrate towards the damaged brain within 4 weeks. The engrafted cells morphologically simulated neurons and expressed NeuN and MAP2, markers specific for neurons. However, their engraft-ment was much less pronounced when the cell suspension was only decanted onto the surface of brain. Therefore, the TGP-BMSC construct transplantation technique may be safer and less invasive than a direct injection of cell suspension or tissue-engineered graft into the injured CNS, because it has no potential risk of inducing additional injury in the host CNS. In other words, the TGP-BMSC construct may act as a noninvasive "biofilm" or "poultice" which includes the donor cells and regenerates the damaged tissue of the host CNS.

In conclusion, this study confirms that surgical transplantation of tissue-engineered BMSCs onto the intact neocortex enhances the engraftment of donor cells around a cerebral infarct. Furthermore, TGP hydrogel, because of its unique biochemical properties, could be a promising candidate as a valuable scaffold in BMSC transplantation for CNS disorders.

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