A combinatorial approach for spinal cord injury repair using multifunctional collagen-based matrices: development, characterization and impact on cell adhesion and axonal growth.

Spinal cord injury is a devastating condition of the central nervous system, in which traditional treatments are largely ineffective due to the complex nature of the injured tissue. Therefore, biomaterial-based systems have been developed as possible alternative strategies to repair the damaged tissue. In the present study, we aimed to design bioactive agent loaded scaffolds composed of two layers with distinct physical properties to improve tissue regeneration. An electrospun layer with aligned nanofibers was made of collagen (Col) Type-I, poly(lactide-co-glycolide) (PLGA) and laminin to promote cell attachment of mesenchymal-like stem cells towards the direction of fibers, while a Col-based second layer was fabricated by plastic compression to act as a releasing system for NT-3 and chondroitinase ABC, so that axonal growth could be stimulated. Results showed that a source of mesenchymal stem cell (MSC)-like cells, adipose tissue-derived stem cells cultured on the fibrous layer of the matrices were able to adhere and proliferate, where the aligned fibers promoted the cell growth in an organized way. Furthermore, the bilayered matrices also promoted dorsal root ganglion neurite outgrowth. The bilayered matrice with Col/PLGA + laminin top layer appears to promote higher neurite growth. Collectively, the designed constructs show promising structural properties and biological performance for being employed as a scaffold for engineering the spinal cord tissue.

Exploiting the impact of the secretome of MSCs isolated from different tissue sources on neuronal differentiation and axonal growth.

Cell transplantation using Mesenchymal stem cell (MSC) secretome have recently been presented as a possible free-based therapy for CNS related disorders. MSC secretome is rich in several bio-factors that act synergically towards the repair of damaged tissues, thus making it an ideal candidate for regenerative applications. Great effort is currently being made to map the molecules that compose the MSC secretome. Previous proteomic characterization of the secretome (in the form of conditioned media - CM) of MSCs derived from adipose tissue (ASC), bone-marrow (BMSC) and umbilical cord (HUCPVC) was performed by our group, where proteins relevant for neuroprotection, neurogenic, neurodifferentiation, axon guidance and growth functions were identified. Moreover, we have found significant differences among the expression of several molecules, which may indicate that their therapeutic outcome might be distinct. Having this in mind, in the present study, the neuroregulatory potential of ASC, BMSC and HUCPVC CM in promoting neurodifferentiation and axonal outgrowth was tested in vitro, using human telencephalon neuroprogenitor cells and dorsal root ganglion explants, respectively. The CM from the three MSC populations induced neuronal differentiation from human neural progenitor cells, as well as neurite outgrowth from dorsal root ganglion explants. Moreover, all the MSC populations promoted the same extent of neurodifferentiation, while ASC CM demonstrated higher potential in promoting axonal growth.