Migration of bone marrow‐derived mesenchymal stem cells induced by tumor necrosis factor‐α and its possible role in wound healing

Abstract

We aimed to investigate the effect of tumor necrosis factor-alpha (TNF-alpha) on the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the migration ability of mesenchymal stem cells (MSCs) in the context of wound healing. We also explored the role of p38 mitogen-activated protein kinase and extracellular signal-regulated kinase (ERK) signaling pathways in the migration of MSCs. MSCs were isolated from the bone marrow and cultured. Immunocytochemistry, Western blotting, and reverse transcription-polymerase chain reaction were used to observe the effect of TNF-alpha on the expression of ICAM-1 and VCAM-1 in MSCs. The chemotaxis effect of TNF-alpha on MSCs was investigated by the trans-well system and the inhibition effect of TNF-alpha using its antibody. Western blotting analysis was used to observe the activation of JAK-STAT and mitogen-activated protein kinase signaling pathways, and ERK was inhibited with PD98059 and p38 with SB203580 to observe the effect of TNF-alpha on MSC migration and ICAM-1 expression. The expression of ICAM-1 could be up-regulated by 50 microg/L TNF-alpha (p<0.05), whereas that of VCAM-1 remained unchanged (p>0.05). Also, TNF-alpha showed a chemotaxis effect by enhancing the migration ability of MSCs (p<0.05). TNF-alpha at 50 microg/L increased the expression of phospho-ERK and phospho-p38, and SB203580, but not PD98059, could suppress the chemotaxis effect and up-regulation of ICAM-1 induced by TNF-alpha in MSCs (p<0.05). Thus, TNF-alpha could up-regulate the expression of ICAM-1 in MSCs and enhance the cells' migration ability, and the p38 signaling pathway might be involved in the TNF-alpha-induced migration ability for a role in wound repair and regeneration.

Highly osteogenic PDL stem cell clones specifically express elevated levels of ICAM1, ITGB1 and TERT

“…It has been shown that ICAM1 plays an important role in direct cell-to-cell contact-mediated signals via mitogen-activated protein kinase (MAPK) pathway including p38, extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) 1/2/3 (Cernuda-Morollon and Ridley 2006, Turowski et al 2005), which could subsequently stimulate osteoblast differentiation of stem/progenitor cells. Fu et al (2009) further suggested that ICAM1 and p38 MAPK also significantly influence the migration of stem cells to their target sites, such as PDL tissue and alveolar bone. These previous evidence, together with our present results, suggest that ICAM1 could also play a significant part in signals initiated by direct cell-to-cell and cell-to-matrix contact, thus subsequently enhancing osteoblast differentiaon of stem cells.…”

“…ICAM1 is an important cell surface adhesion molecule found in many cell types including in stem/progenitor cells and osteoblasts (Fu et al 2009, Tanaka et al 1995. Several lines of evidence support that ICAM1-mediated direct cell contact has a major impact on a wide range of biological responses including cell differentiation (Gortz et al 2004, Long et al 1995, Olsen et al 1988, Saho et al 2003, Tanaka et al 1995.…”

Secretion of immunoregulatory cytokines by mesenchymal stem cells

“…Strengthening the adhesion of MSCs to T cells via ICAM-1 proportionally potentiates the function of MSCs represented by lagging of T cells proliferation [204] . Besides the direct role of ICAM-1 in MSCs interaction with immune cells, the importance of membrane expression of ICAM-1 spans MSCs migration [208] , proliferation and differentiation capacity [209] . Seemingly indirectly related, the essence of the processes like migration, proliferation and differentiation of MSCs is also regulated by the inflammatory environment [66] .…”

RECENT RESEARCH ON THE GROWTH PLATE: Mechanisms for growth plate injury repair and potential cell-based therapies for regeneration

“…Utilising a TNFa antagonist in a rat growth plate injury model, Zhou et al (2006) found that blocking TNFa resulted in a clear delay in the subsequent mesenchymal infiltration response and a reduction of the proliferation of these cells . Similarly, separate studies looking at the role of TNFa during bone fracture repair and wound repair have also found that its inhibition leads to a significant delay in overall mesenchymal progenitor or stem cell (MSC) infiltration and subsequent healing (Gerstenfeld et al 2001, Fu et al 2009). More studies have reported the importance of TNFa in regulating recruitment of MSC, their proliferation and differentiation (Barnes et al 1999, Martin et al 2003, Dimitriou et al 2005.…”