Stem Cells Dev. 2014 Sep 22. [Epub ahead of print]

Mesenchymal stromal cells derived from blood vessels or avascular tissues: What is the better choice to support endothelial cell function?

König J¹, Weiss G, Rossi D, Wankhammer K, Reinisch A, Kinzer M, Huppertz B, Pfeiffer D, Parolini O, Lang I.

Abstract

Mesenchymal stromal cells (MSC) are promising tools for therapeutic revascularization of ischemic tissues and for support of vessel formation in engineered tissue constructs. Recently, we could show that avascular-derived MSC from placental amnion release soluble factors that exhibit survival-enhancing effects on endothelial cells. We hypothesize that MSC derived from placental blood vessels might have even more potent angiogenic effects. Therefore, we isolated and characterized MSC from placental chorionic blood vessels (bv-MSC) and tested their angiogenic potential in comparison to amnion-derived avascular MSC (av-MSC). Bv-MSC express a very similar surface marker profile compared to av-MSC and could be differentiated towards the adipogenic and osteogenic lineage. Bv-MSC exert immunosuppressive properties on peripheral blood mononuclear cells suggesting that they are suitable for cell transplantation settings. Conditioned medium from av-MSC and bv-MSC significantly enhanced endothelial cell viability, whereas only conditioned medium from bv-MSC significantly increased endothelial cell migration and network formation (Matrigel assay). Angiogenesis array analysis of av- and bv-MSC-conditioned medium revealed a similar secretion pattern of angiogenic factors including angiogenin, interleukin-6 and -8, TIMP-1&2. ELISA analysis showed that, in contrast to av-MSC, bv-MSC secreted VEGF. In direct co-culture with bv-MSC, endothelial cells showed a significantly increased formation of vessel-like structures compared to av-MSC. With regard to therapeutic treatment, bv-MSC and particularly their conditioned medium might be valuable to stimulate angiogenesis especially in ischemic tissues. Av-MSC and their conditioned medium could be beneficial in conditions when it is required to promote the survival and stabilization of blood vessels without the risk of unmeant angiogenesis.