Reparative effect of mesenchymal stromal cells on endothelial cells after ischemic and inflammatory injury
M. Eijken, B. Jespersen, B. Moller, C.C. Baan, M. Hoogduijn, A. Merino, R.J. Ploeg, J.M. Sierra Parraga
Wednesday 4 march 2020
17:00 - 17:10h
at Joep Nicolas zaal
Parallel session: Parallel sessie VII – Basale- en Klinische abstracts
Background: Renal endothelium is damaged by ischemia reperfusion injury during transplantation as a result ischemia-reperfusion injury. It has been shown that mesenchymal stromal cells (MSC) are able to repair injured renal tissue. However, the mechanisms behind these MSC effects are still poorly understood.
Therefore, our objective was to evaluate the role of MSC in repairing injured endothelium and to determine the specific interactions involved in this process. The role of physical interaction and cytokine secretion in the reparative action of MSC was studied as well as its molecular mechanisms.
Methods: Human umbilical vein endothelial cells (HUVEC) were submitted to hypoxic and inflammatory insult with TNF-a during culture. HUVEC became activated, which was proven by an increased expression of activation molecules such as CD54, CD62e and HLA-II. Consequently, an increase of 20% in the adherence of MSC to HUVEC was observed. Moreover, an increase of 20% on MSC migratory capacity towards injured HUVEC was observed, the same increase which was observed in their ability to transmigrate through HUVEC monolayers.
Results: MSC were added to culture either prior or after injuring the endothelial cells. Once MSC were in contact with HUVEC, the oxidative stress of HUVEC decreased as observed by a decrease in reactive oxygen species, their proliferative status improved and MSC restored the endothelial monolayer stability to levels close to those from healthy HUVEC.
To determine whether physical interaction or soluble factors released by MSC are fundamental for MSC regenerative capacity we performed experiments in a Boyden chamber system and we observed that both were required to achieve the full reparative effect of MSC. Moreover, we observed an increase in the expression of CD44 and CD29 adhesion molecules on MSC membrane as well as their ligands CD62e and CD106 on HUVEC membrane.
Conclusions: We conclude that MSC are able to prevent and repair the injury caused by both ischemic and inflammatory injury on HUVEC via a mechanism that requires both physical and paracrine interaction between MSC and HUVEC. We are currently studying possible effector proteins for cell-to-cell interaction of MSC and HUVEC as specific molecules involved in this reparative effect which will allow us to target them to further improve the regenerative effects of MSC therapy on injured endothelial cells.
