Juxtaposition of Mesenchymal Stem Cells with Endothelial Progenitor Cells Promoted Angiogenic Potential Inside Alginate-Gelatin Microspheres

Purpose: Here, we investigated the angiogenic potential of endothelial progenitor cells juxtaposed with mesenchymal stem cells (MSCs) inside alginate-gelatin microspheres with stromal derived factor-1α (SDF-1 α) for 7 days. Methods: Six encapsulated groups were allocated including endothelial progenitor cells (EPCs), EPCs/SDF-1α, MSCs, MSCs/SDF-1α, EPCs+MSCs and EPCs+MSCs/SDF-1α. Cells were encapsulated with a mixture of 1% alginate and 2% gelatin hydrogel. Cell survival was examined by MTT assay. Endothelial differentiation was determined by flow cytometry and ELISA. Tubulogenesis assay and Ac-Dil-LDL uptake were used to detect functional activity. Cell migration was analyzed by Transwell insert and gelatin zymography analyses. By using real-time polymerase chain reaction (PCR), we measured the transcription of Akt and PK1. Results: We found an increase in cell viability in MSCs/SDF-1α microspheres compared to EPCs group (P <0.05). EPC/MSCs co-culture contributed to the increase of CD133+ cells while we found high CD31 levels in MSCs group (P <0.05). Juxtaposition of EPC with MSCs increased tubulogenesis compared to SDF-1a-free condition (P <0.001). SDF-1α had the potential to increase in AC-LDL uptake in MSCs and EPCs/MSCs groups. Cells migration and MMP-9 activities increased after treatment with SDF-1α. SDF-1α upregulated PK1 and Akt in encapsulated cells, especially in a co-culture system. Conclusion: Alginate-gelatin microspheres could alter the angiogenic potential of progenitor cells in the presence of SDF-1α