Year: 2008
Type: article
Abstract: Mesenchymal stem cells (MSCs), which potentially transdifferentiate into multiple cell types, are increasingly reported to be beneficial in models of organ system injury. However, the molecular mechanisms underlying interactions between MSCs and host cells, in particular endothelial cells (ECs), remain unclear. We show here in a matrigel angiogenesis assay that MSCs are capable of inhibiting capillary growth. After addition of MSCs to EC-derived capillaries in matrigel at EC:MSC ratio of 1:1, MSCs migrated toward the capillaries, intercalated between ECs, established Cx43-based intercellular gap junctional communication (GJC) with ECs, and increased production of reactive oxygen species (ROS). These events led to EC apoptosis and capillary degeneration. In an in vivo tumor model, direct MSC inoculation into subcutaneous melanomas induced apoptosis and abrogated tumor growth. Thus, our findings show for the first time that at high numbers, MSCs are potentially cytotoxic and that when injected locally in tumor tissue they might be effective antiangiogenesis agents suitable for cancer therapy.
Source: Blood
Institution: Columbia University
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G382402740, G4390587119, G6077820604, ALVEOLO-CAPILLARY SIGNALING IN LUNG IMMUNOLOGY, MICROPUNCTURE STUDIES OF LUNG WATER AND SOLUTE EXCHANGE, NOVEL MECHANISMS OF ALVEOLAR INFLAMMATION., Mechanistic role of membrane pore formation in lung-endothelial barrier failure due to blood-borne pathogens.
OpenAlex ID: W2058855830