TNF-alpha enhances engraftment of mesenchymal stem cells into infarcted myocardium

Abstract

TNF-alpha released from ischemic heart after acute MI increases the production of other cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). Activation of nuclear factor kappa B (NF-kappa B) by TNF-alpha , up-regulates the expression of molecules which are involved in inflammation and cell adhesion. For these reasons, we assessed the extent that treatment of MSC with tumor necrosis factor (TNF)-alpha modifies the characteristics of MSC, important to their engraftment in experimental myocardial infarct. Here, we show that pre-treatment of MSC prior to transplantation with tumor necrosis factor (TNF)-alpha increases adhesiveness, and migration of MSC in vitro and leads to increased expression of bone morphogenetic protein (BMP)-2 by MSC. Moreover, this treatment increases the rate of engraftment of MSC and improves recovery of cardiac function after myocardial infarction. These insights might provide better strategies for the treatment of myocardial infarction.

Mesenchymal stem cells: a new strategy for immunosuppression and tissue repair

“…MSCs can up-regulate both intracellular and membrane expression of CXCR4 after a short pretreatment with cytokines, gaining enhanced engraftment ability to the bone marrow of irradiated NOD/SCID mice, and transplantation of cytokines-treated MSCs results in faster hematological recovery [74]. Another recent study showed that TNF-α pretreatment before transplantation could increase MSC engraftment efficiency and improve recovery of cardiac function after cardiac infarction [81].…”

Alarmins: awaiting a clinical response

“…This dual role is exemplified by the proinflammatory cytokine TNF-α. While sustained upregulation has a destructive role in many inflammatory conditions, TNF-α also acts as a growth factor for myelin-producing cells (114), differentiation factor for mesenchymal stem cells (115), and potential therapeutic in the infarcted myocardium (116) or bone fractures (117).…”

TNF-α modulates the migratory response of mesenchymal stem cells to TRAIL

“…While most initial studies underlined a negative prognostic role of elevated levels of circulating TNF-a in the physiopathology of heart failure (HF) in AMI patients, other more recent studies have suggested that TNF-a might exert a beneficial role by increasing the recruitment of mesenchymal stem cells (MSC) [5,6]. Interestingly, one of the major transcriptional targets of TNF-a is osteoprotegerin (OPG), a soluble member of the TNF receptor superfamily [7,8].…”