Figure 5.

Gene expression changes are continuously acquired during long-term culture. In the overlap of senescence-associated gene expression changes of FBS-MSC, pHPL-MSC and MSC-M1, there were eight genes that were differentially expressed by more than two-fold in each of the three datasets: PTPL1-associated RhoGAP 1 (PARG1), serpin peptidase inhibitor (SERPINE1), cyclin-dependent kinase inhibitor 2B (CDKN2B), netrin 4 (NTN4), toll interacting protein (TOLLIP) and brain-derived neurotrophic factor (BDNF) were senescence-induced. Minichromosome maintenance complex component 3 (MCM3) and pleiotrophin (PTN) were senescence-repressed. Analysis of microarray data revealed that most of these changes increase with every passage (A–C; for MSC-M1 data of serial passages of donor 1 were reanalyzed from our previous work).¹⁹ These gene expression changes were also validated by RT-PCR (D–F; mean of two biological replicas are presented).