Adipose-derived endothelial and mesenchymal stem cells enhance vascular network formation on three-dimensional constructs in vitro

Alina Freiman, Yulia Shandalov, Dekel Rozenfeld, Erez Shor, Sofia Segal, Dror Ben-David, Shai Meretzki, Dana Egozi*, Shulamit Levenberg

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

82 Scopus citations


Background: Adipose-derived mesenchymal stem cells (MSCs) have been gaining fame mainly due to their vast clinical potential, simple isolation methods and minimal donor site morbidity. Adipose-derived MSCs and microvascular endothelial cells have been shown to bear angiogenic and vasculogenic capabilities. We hypothesized that co-culture of human adipose-derived MSCs with human adipose-derived microvascular endothelial cells (HAMECs) will serve as an effective cell pair to induce angiogenesis and vessel-like network formation in three-dimensional scaffolds in vitro. Methods: HAMECs or human umbilical vein endothelial cells (HUVECs) were co-cultured on scaffolds with either MSCs or human neonatal dermal fibroblasts. Cells were immunofluorescently stained within the scaffolds at different time points post-seeding. Various analyses were performed to determine vessel length, complexity and degree of maturity. Results: The HAMEC:MSC combination yielded the most organized and complex vascular elements within scaffolds, and in the shortest period of time, when compared to the other tested cell combinations. These differences were manifested by higher network complexity, more tube alignment and higher α-smooth muscle actin expression. Moreover, these generated microvessels further matured and developed during the 14-day incubation period within the three-dimensional microenvironment. Conclusions: These data demonstrate optimal vascular network formation upon co-culture of microvascular endothelial cells and adipose-derived MSCs in vitro and constitute a significant step in appreciation of the potential of microvascular endothelial cells and MSCs in different tissue engineering applications that can also be advantageous in in vivo studies.

Original languageEnglish
Article number5
JournalStem Cell Research and Therapy
Issue number1
StatePublished - 11 Jan 2016
Externally publishedYes


FundersFunder number
Ministry of Industry and Trade, Israel
Horizon 2020 Framework Programme281501, 640579
European Research Council


    • Adipose MSCs
    • Microvascular ECs
    • PLLA/PLGA scaffolds
    • Tissue engineering
    • Vascularization


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