Glucose Delivery System Based-Hydrogel Composite Scaffold for enhancing MSC survival

In the context of cell-based regenerative medicine, exoge-nously administered mesenchymal stromal cells (MSCs) ex-hibited a poor survival rate. A possible explanation for this limited cell survival is that, upon implantation, MSCs encoun-ter a harsh ischemic microenvironment characterized by low oxygen tension and nutrient deprivation. This issue can be overcome by in situ supplying glucose that acts as the main metabolic fuel for MSCs in hypoxia and enhances their sur-vival (Deschepper et al.2011 and 2013). The objective of the study is to engineer a tissue-construct that provides sufficient level of glucose to MSCs and enhances their survival when transplanted in vivo. To this aim, hydrogels containing fibrin, starch (a polymer of glucose) and AMG (an enzyme that re-lease glucose from starch) were formulated. These injectable, self-supported hydrogels released glucose amounts in ac-cordance with that required by hMSCs for their survival. In vitro, under near anoxia, MSCs loaded in fibrin/starch/AMG hydrogels exhibited a survival rate 115 times higher than the one loaded in fibrin hydrogels, after 14 days. Moreover, when ectopically implanted in nude mice, luciferase-labelled hM-SCs loaded in fibrin/starch/AMG hydrogels exhibited a sig-nificant improvement of their viability (x4 after 14 days) in comparison to hMSCs loaded in fibrin gels as demonstrated by the follow-up of the luciferase activity by bioluminescence imaging. These data were further substantiated by monitoring the number of hMSCs remaining in the hydrogels implanted ectopically in mice. At day 14 days, fibrin / AMG / starch scaffolds contained 7.5 times more viable hMSCs than fibrin hydrogels. This work establishes for the first time that a con-struct based on a fibrin/starch/AMG hydrogel delivers glucose over time and enhances the survival of hMSCs. Most inter-estingly, the data obtained with hMSCs are now extended to adipose-derived MSCs and myoblasts.

Keywords:

Mesenchymal Stem Cell , Cell Survival , Bone Repair.