Sorour Nemati - Chemical Engineering Faculty, Sahand University of Technology, Tabriz, Iran
Aysa Rezabakhsh - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
Ali Baradar Khoshfetrat - Chemical Engineering Faculty, Sahand University of Technology, Tabriz, Iran
Alireza Nourazarian - Department of Biochemistry and Clinical Laboratories, Tabriz University of Medical Sciences, Tabriz, Iran

Background and Aim: Up to present, numerous attempts have beencollected in the favor of cell-based therapies by using sophisticatedmethodologies and delivery approaches. Micro-capsules have thepotential to provide safe micro-environment for cells delivery duringtransplantation in a physiological 3D milieu.Methods: Here, we investigate the impact of alginate gelatinencapsulation on angiogenic potential of human endothelial cells after 5days. Human umbilical vein endothelial cells were encapsulated by thealginate-gelatin substrate and kept in vitro for 5 days. Cell survival assay(MTT) and autophagy PCR array analysis were used to study HUVECssurvival rate. To monitor angiogenesis capacity, cell distribution of Tie-1,VEGFR-1, and VEGFR-2 and Tie-2, were measured by ELISA. In additionto in vitro tubulogenesis assay, we measured the protein level of VEcadherinby Western blotting. The migration of encapsulated HUVECswas confirmed by measuring MMP-2 and MMP-9 activity via gelatinzymography. The in vivo angiogenic potential of encapsulated HUVECswas analyzed in immune-compromised mouse implant model during 7days post-transplantation.Results: Encapsulation increased HUVECs cell survival and proliferationrate. Compared to the control, no significant differences were observedin the autophagic response of encapsulated cells (P > 0.05). The celldistribution of Tie-1, Tie-2, VEGFR-1, and VEGFR-2 were induced butdid not reach significant levels. Encapsulation suppressed MMP-2, -9activities while increased the VE-cadherin peptide in enclosed cells(P < 0.05). Moreover, an enhanced in vivo angiogenic response ofencapsulated HUVECs was evident as compared to non-capsulated cells(P < 0.05).Conclusion: Data suggest that alginate-gelatin encapsulation induces theangiogenic response of endothelial lineage in the in vivo and in vitroconditions.

Alginate-gelatin encapsulation; Angiogenesis; Human endothelial cells; Migration; Receptor tyrosine kinases; VE-cadherin