%0 Journal Article
%T DNA Methylation Changes during In Vitro Propagation of Human Mesenchymal Stem Cells: Implications for Their Genomic Stability?
%A Angela Bentivegna
%A Mariarosaria Miloso
%A Gabriele Riva
%A Dana Foudah
%A Valentina Butta
%A Leda Dalprš€
%A Giovanni Tredici
%J Stem Cells International
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/192425
%X Mesenchymal stem cells (MSCs) hold great promise for the treatment of numerous diseases. A major problem for MSC therapeutic use is represented by the very low amount of MSCs which can be isolated from different tissues; thus ex vivo expansion is indispensable. Long-term culture, however, is associated with extensive morphological and functional changes of MSCs. In addition, the concern that they may accumulate stochastic mutations which lead the risk of malignant transformation still remains. Overall, the genome of human MSCs (hMSCs) appears to be apparently stable throughout culture, though transient clonal aneuploidies have been detected. Particular attention should be given to the use of low-oxygen environment in order to increase the proliferative capacity of hMSCs, since data on the effect of hypoxic culture conditions on genomic stability are few and contradictory. Furthermore, specific and reproducible epigenetic changes were acquired by hMSCs during ex vivo expansion, which may be connected and trigger all the biological changes observed. In this review we address current issues on long-term culture of hMSCs with a 360-degree view, starting from the genomic profiles and back, looking for an epigenetic interpretation of their genetic stability. 1. Properties of Mesenchymal Stem Cells Mesenchymal stem cells (MSCs) are multipotent adult stem cells with a great therapeutic potential in tissue engineering, regenerative medicine, autoimmune diseases, and pathologies characterized by chronic inflammatory processes [1, 2]. MSCs from bone marrow (BM-MSCs) are the best characterized adult stem cells but MSC-like populations have been isolated from several tissues such as adipose tissue, umbilical cord blood, skin, skeletal muscle, and also from dental tissues as dental pulp, exfoliated deciduous teeth, and periodontal ligament [3, 4]. Compared with other stem cell types, such as embryonic stem cells (ESCs) and neural stem cells, MSCs have several advantages and no ethical concerns limit their use. MSCs can be easily isolated, have a capacity for extensive proliferation and self-renewal, present a low risk of tumorigenicity, and can be used autologously. Moreover MSCs are considered immunoprivileged because they express low level of MHC-I molecules but not MHC-II and costimulatory molecules CD80, CD86, and CD40 [5]. The therapeutic effect of MSCs is mainly based on some key properties: (1) MSCs are able to differentiate not only into mesodermal lineages (osteogenic, adipogenic, and chondrogenic lineages) but also towards endodermal or ectodermal
%U http://www.hindawi.com/journals/sci/2013/192425/