Reparative effect of mesenchymal stromal cells on endothelial cells after hypoxic and inflammatory injury

Abstract

Background: The renal endothelium is a prime target for ischemia-reperfusion injury (IRI) during donation and transplantation procedures. Mesenchymal stromal cells (MSC) have been shown to ameliorate kidney function after IRI. However, whether this involves repair of the endothelium is not clear. Therefore, our objective is to study potential regenerative effects of MSC on injured endothelial cells and to identify the molecular mechanisms involved. Methods: Human umbilical vein endothelial cells (HUVEC) were submitted to hypoxia and reoxygenation and TNF-α treatment. To determine whether physical interaction or soluble factors released by MSC were responsible for the potential regenerative effects of MSC on endothelial cells, dose-response experiments were performed in co-culture and transwell conditions and with secretome-deficient MSC. Results: MSC showed increased migration and adhesion to injured HUVEC, mediated by CD29 and CD44 on the MSC membrane. MSC decreased membrane injury marker expression, oxidative stress levels, and monolayer permeability of injured HUVEC, which was observed only when allowing both physical and paracrine interaction between MSC and HUVEC. Furthermore, viable MSC in direct contact with injured HUVEC improved wound healing capacity by 45% and completely restored their angiogenic capacity. In addition, MSC exhibited an increased ability to migrate through an injured HUVEC monolayer compared to non-injured HUVEC in vitro. Conclusions: These results show that MSC have regenerative effects on injured HUVEC via a mechanism which requires both physical and paracrine interaction. The identification of specific effector molecules involved in MSC-HUVEC interaction will allow targeted modification of MSC to apply and enhance the therapeutic effects of MSC in IRI.

TNFα priming through its interaction with TNFR2 enhances endothelial progenitor cell immunosuppressive effect: new hope for their widespread clinical application

“…CB-ECFCs were incubated with increasing doses of TNFα. After 24 h, cells were analyzed for the expression of ICAM, VCAM and TIE-2 pro-inflammatory/injury markers [ 51 ]. We observed that 0.01 and 0.1 ng/ml of TNFα provided low inflammation.…”

Tropoelastin improves adhesion and migration of intra-articular injected infrapatellar fat pad MSCs and reduces osteoarthritis progression

“…Here, our results showed that compared with NS, HA, and PRP solution, IPFP-MSCs suspended in TE solution had strong adhesion at early stages. Previous studies normally analyzed number of adherent cells, with no further analysis of the adhesion morphology of MSCs [ 51 , 52 ]. In this study, adhesion area and height of IPFP-MSCs at 2 h were detected by SEM and Pro-film 3D scanning.…”

Expanded Hemodialysis Therapy Ameliorates Uremia-Induced Systemic Microinflammation and Endothelial Dysfunction by Modulating VEGF, TNF-α and AP-1 Signaling

“…Our manuscript focuses on readout of the TNFa, sTNF-R1/ R2, AP1/cFOS, and VEGF signaling axis in the context of detrimental effects of uremia on microvascular ECs and amelioration thereof by employing novel dialysis filters with improved molecular cutoff. For better understanding to readers, we have focused on these main mediators, but in principle the list of studied markers could be expanded to many other markers indicative of endothelial maladaptation/injury/damage markers, such as endothelial E-Selectin (ELAM-1), ICAM-1, VCAM-1, IL-6, IL-8, Tie-2 and the production of reactive oxygen species (ROS), as outlines in other studies on endothelial inflammation (37,46,(57)(58)(59).…”