I kappa B kinase 2 (IKK-2) mediates tumor necrosis-factor alpha (TNF alpha) induced invasion of human mesenchymal stem cell (hMSC) to sites of tissue injury. Suppressing IKK-2 activity leads to reduced expression of proteolytic enzymes and impaired invasive capacity. In order to further reveal mechanisms of hMSC recruitment, we here aimed to analyse the impact of IKK-2 on two-dimensional migration upon TNF alpha stimulation in contrast to three-dimensional invasion. An immortalized hMSC line (SCP-1) was transduced with a dominant-negative mutant of I kappa B kinase 2 (SCP-1 dnIKK). Migration was assessed using a linear-gradient chemotaxis chambers by time-lapse analysis. Invasive capacity through human extracellular matrix was analysed using transwell invasion assays. RT-PCR confirmed increased IKK-2 expression levels in SCP-1 dnIKK cells, while TNF alpha receptor I and II expression was not altered. Invasion upon TNF alpha stimulation was significantly reduced by 78% in SCP-1 dnIKK. In contrast, migration was significantly increased, represented by a 60% elevated forward migration index and a 2.1-fold higher mean dislocation of the center of mass towards TNF alpha. In conclusion, our data confirms the impact of IKK-2 in TNF alpha dependent hMSC recruitment. Interestingly, reducing IKK-2 function increases two-dimensional migration towards TNF alpha, while invasive capacity is impaired. These findings contribute to a deeper understanding of MSC's biological properties orchestrating the complex processes of stem cell recruitment and homing. (C) 2013 Elsevier Inc. All rights reserved.