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-a 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.

Bioinformatic Exploration of Hub Genes and Potential Therapeutic Drugs for Endothelial Dysfunction in Hypoxic Pulmonary Hypertension

“…The results of GO analysis suggested that the EDGs were markedly enriched in the migration and adhesion (actin filament organization, ameboidal-type cell migration, cellsubstrate adhesion, actin filament binding, extracellular matrix structural constituent, and focal adhesion) and cancer-like response (proteoglycans in cancer), which was in accordance with pathogenesis mentioned before [18,19]. Additionally, KEGG analysis indicated that PI3K-Akt signaling pathway was significantly enriched, which was consistent with the previous demonstration that hypoxia response involves crosstalk with proliferation and apoptosis mechanisms [20,21].…”

miRNA-126-3p carried by human umbilical cord mesenchymal stem cell enhances endothelial function through exosome-mediated mechanisms in vitro and attenuates vein graft neointimal formation in vivo

“…Although the underlying mechanisms are unclear, it is now nearly universally accepted that the therapeutic effects of transplanted MSCs on tissue repair is not only due to their differentiation potential into appropriate cell types that repairs and replaces the damaged tissues, but rather due to enhancing the function of resident cells via paracrine signaling actions [ 9 ]. There is accumulating evidence suggesting that MSCs synthesize and secrete multiple bioactive molecules such as angiogenic factors, growth factors and cytokines which have beneficial effects of endothelial cell behavior in vitro and induce angiogenic programing in vivo [ 10 , 11 ].…”

Targeting inorganic nanoparticles to tumors using biological membrane‐coated technology

“…85 MSCs play a role in tumor progression by secreting relevant factors and hormones that act on target tissues. 50 The unique properties of MSCs are mainly due to their membranes containing a variety of receptors, including cytokine receptors, chemokine receptors, growth factor receptors, cell matrix receptors, and receptors for cell-cell interactions. Therefore, MSC membranes are an ideal potential vehicle for establishing drug delivery systems.…”

“…However, some evidences suggest that MSCs can also promote tumor growth through immune regulation and TME remodeling 85 . MSCs play a role in tumor progression by secreting relevant factors and hormones that act on target tissues 50 . The unique properties of MSCs are mainly due to their membranes containing a variety of receptors, including cytokine receptors, chemokine receptors, growth factor receptors, cell matrix receptors, and receptors for cell–cell interactions.…”