Implicaciones del calcio extracelular y su receptor en mebrana (CaSR) en la angiogénesis y la osteogénesis. Relevancia en ingeniería tisular.

Abstract

Bone injury is a major health problem nowadays. Bone tissue engineering is a promising strategy to solve it. In this field many reports pointed out the role of scaffolds containing a calcium phosphate glass, such as G5, in the promotion of bone regeneration. These kinds of biomaterials release Ca2+ during degradation. Moreover, extracellular calcium (Ca2+0) is able to activate a special extracellular receptor called Calcium Sensing Receptor (CaSR), which can modulate migration, chemotaxis and differentiation. In that sense, present work aims to evaluate the role of extracellular calcium and CaSR as key factor in the induction of bone regeneration. We isolated endothelial progenitor cells (EPCs) and Mesenchymal Stromal cells (MSCs) from young rat’s bone marrow and they were stimulated with 10 mM Ca2+0. Results provided strong evidences about the role of Ca2+0 and CaSR in the modulation of chemotaxis, and angiogenic differentiation on EPCs, whilst on MSCs calcium exerted osteoinduction and proliferation through the CaSR. Furthermore, using biodegradable releasing calcium composite (PLA/G5) was measured the ability of that kind of biomaterials in the induction of bone and blood vessels formation in vivo. Finally, using a shell-less chick embryo model was compared the effect of the Ca2+0 and the ionic compound released by PLA/G5, demonstrating that the released Ca2+0 is the key factor in the promotion of angiogenesis and bone formation in vivo. The knowledge developed during this project will be a valuable tool to enhance the efficiency of biomaterials used in bone tissue engineering