Degenerative disc disease (DDD) is a major cause of chronic low back pain. For mild/intermediate DDD, regeneration by injecting adipose stem cells (ASCs) into the nucleus pulposus (NP) may be considered. The goal of this study is to investigate whether NP cells can direct ASCs towards the NP phenotype. Interactions between NP cells and ASCs were studied in transwell co-cultures, employing both monolayer and micromass configurations. Micromass culturing significantly up-regulated aggrecan and collagen type II gene expression in NP cells. In ASCs, expression of these genes and of osteopontin, collagen type I and PPAR-gamma were not significantly affected. Strikingly, only when both cell types were micromass-cultured, ASCs could be chondrogenically differentiated, as shown by induction of collagen type II and aggrecan, and concomitant down-regulation of osteopontin, collagen type I and PPAR-gamma. We conclude that ASCs can be directed towards the NP cell-like phenotype by soluble factor(s) secreted by NP cells. (c) 2007 Elsevier Inc. All rights reserved.