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IBEC Seminar: Alexandra P. Marques
Friday, June 12, 2015 @ 10:00 am–11:00 am
Driving skin wound healing: stem cells and extracellular matrix role
Alexandra P. Marques, 3B’s Research Group, University of Minho, Portugal
Wound care products have evolved into skin tissue engineered substitutes, which despite the longest history of application and the highest record of marketing, proved to represent replacement strategies instead of promoting tissue regeneration.
Current research indicates that the interactions between resident progenitor cells and their niche dictate the triggering of skin regeneration pathway. In alignment, mesenchymal stem cells (MSCs)-based therapies, have been proposed to enhance cutaneous wound healing. The rationale lies on transplanted cells ability to interact/respond to the wound microenvironment, which is advantageous when compared to the exogenous administration of healing factors. However, the involved mechanisms are still elusive and poor outcomes were achieved in terms of attainment of functional skin tissue due to low cell survival rates, and poor engraftment or cell fusion upon transplantation. Extracellular matrix (ECM)-mimicking is currently seen as the “Holy Grail” of Tissue Engineering in the sense that by recreating natural tissues microenvironments researchers will be able to increase the residence time and consequently the action of the transplanted cells and thus uncover “therapeutic niches”.
Under this context we have been exploring two perspectives; one takes advantage of the tunable ECM-like properties along with the 3D support that hydrogels can provide, and the second benefits from an intact native ECM offered by cell sheet engineering technology. Hydrogels features such as high hygroscopic nature, tunable elasticity and facilitated mass transportation, render such materials attractive for the development of skin ECM-analogues. Although succeeding in improved cell engraftment, hydrogels fail to provide biological instructive cues as well as cell adhesion sites, only overcome by cell adhesive peptides bonding to polymers backbone. We developed a new method of processing gellan gum-based materials, having as start material gellan gum-based hydrogels, to obtain structures that exhibit features of both sponges and hydrogels depicting intrinsic cell-adhesive properties. By creating constructs comprising adipose tissue cells and artificial and natural ECM we were able to demonstrated that skin healing is dependent on tissue engineered constructs self cell-cell and cell-ECM interactions, as well as on constructs cell-cell interactions and paracrine signaling with resident cells. In particular, our results suggest that cell-ECM and cell-cell interactions have a dramatic effect over re-epithelialisation. In opposition, neo-vascularisation did not seem to be dependent on the nature of the cell-ECM interactions, but was significantly improved with the incorporation of microvascular endothelial cells.
Ultimately the generation of knowledge on how to direct skin regeneration lead the creation of “off-the-shelf” 3D stem cell-based engineered products inspired by the role of wound healing microenvironments.