Replicative Senescence of Mesenchymal Stem Cells: A Continuous and Organized Process

摘要: Mesenchymal stem cells (MSC) comprise a promising tool for cellular therapy. These are usually culture expanded prior to their application. However, precise molecular definition of MSC and the sequel long-term in vitro yet unknown. In this study, we have addressed impact replicative senescence on human preparations. Within 43 77 days cultivation (7 12 passages), demonstrated morphological abnormalities, enlargement, attenuated expression specific surface markers, ultimately proliferation arrest. Adipogenic differentiation potential decreased whereas propensity osteogenic increased. mRNA profiling revealed consistent pattern alterations global gene signature at different passages. changes not restricted later passages, but continuously acquired with increasing Genes involved cell cycle, DNA replication repair significantly down-regulated late from chromosome 4q21 were over-represented among differentially regulated transcripts. Differential 10 genes has been verified independent donor samples as well that isolated under conditions. Furthermore, miRNA an up-regulation hsa-mir-371, hsa-mir-369-5P, hsa-mir-29c, hsa-mir-499 hsa-let-7f upon propagation. Our studies indicate preparations is continuous process starting first passage onwards. This includes far reaching phenotype, potential, patterns, profiles need be considered therapeutic application