Impairment of endothelial cell differentiation from bone marrow–derived mesenchymal stem cells: New insight into the pathogenesis of systemic sclerosis

Abstract

Objective. Systemic sclerosis (SSc) is a disorder characterized by vascular damage and fibrosis of the skin and internal organs. Despite marked tissue hypoxia, there is no evidence of compensatory angiogenesis. The ability of mesenchymal stem cells (MSCs) to differentiate into endothelial cells was recently demonstrated. The aim of this study was to determine whether impaired differentiation of MSCs into endothelial cells in SSc might contribute to disease pathogenesis by decreasing endothelial repair.Methods. MSCs obtained from 7 SSc patients and 15 healthy controls were characterized. The number of colony-forming unit-fibroblastoid colonies was determined. After culture in endothelial-specific medium, the endothelial-like MSC (EL-MSC) phenotype was assessed according to the surface expression of vascular endothelial growth factor receptors (VEGFRs). Senescence, chemoinvasion, and capillary morphogenesis studies were also performed.Results. MSCs from SSc patients displayed the same phenotype and clonogenic activity as those from controls. In SSc MSCs, a decreased percentage of VEGFR-2؉, CXCR4؉, VEGFR-2؉/CXCR4؉ cells and early senescence was detected. After culturing, SSc EL-MSCs showed increased expression of VEGFR-1, VEGFR-2, and CXCR4, did not express CD31 or annexin V, and showed significantly decreased migration after specific stimuli. Moreover, the addition of VEGF and stromal cell-derived factor 1 to cultured SSc ELMSCs increased their angiogenic potential less than that in controls.Conclusion. Our data strongly suggest that endothelial repair may be affected in SSc. The possibility that endothelial progenitor cells could be used to increase vessel growth in chronic ischemic tissues may open up new avenues in the treatment of vascular damage caused by SSc.

Trafficking of Multipotent Mesenchymal Stromal Cells from Maternal Circulation Through the Placenta Involves Vascular Endothelial Growth Factor Receptor-1 and Integrins

“…Previous data indicate the presence of a small but significant population of mesenchymal stem cells in the blood circulation of adult women [10,42]. Trafficking of maternal MSCs to the fetus during pregnancy has not been demonstrated.…”

Vascular endothelial growth factor is highly expressed in muscle tissue of patients with polymyositis and patients with dermatomyositis

“…The possibility of systemic production is supported by the increased serum levels of VEGF in our patients with myositis. High serum levels of VEGF have also been recorded in other autoimmune diseases (35)(36)(37). The source of serum VEGF in these conditions is still not clarified but may be platelets (38), inflammatory cells (39), or endothelial cells (35).…”

Multipotent mesenchymal stromal cells for autoimmune diseases: teaching new dogs old tricks

“…85 MSCs from human autoimmune disease Autologous BM-derived MSCs have been shown to be potently antiproliferative to stimulated T-cells from normal participants and autoimmune (RA, SSc, Sjoegren's, SLE) patients, 86 and in SSc patients these MSCs were normal with respect to proliferation, clonogenicity and differentiation to bone and fat. 87 However, one group has shown defective differentiation into endothelial precursors in BM-derived MSCs from SSc patients, 88 which should be considered when choosing autologous or allogeneic MSC sources for SSc treatment. In another study, MSCs isolated from MS patients exhibit the same properties of MSCs from healthy donors in terms of proliferation, phenotype, in vitro differentiation and immunosuppressive ability.…”