Senescence of mesenchymal stem cells and its impact on clinical applications

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Isla, Natalia De | Targa, Laurie | Charif, Naceur | Roeder, Émilie | Cauchois, Ghislaine | Stoltz, Jean-François | Rubio, Marie-Thérèse | Bensoussan, Danièle

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International audience. Endogenous and exogenous stresses could induce senescence, a phenomenon through which the capacity of cell division, growth, and function is lost. Even if senescence is considered a barrier against cancer since it blocks the proliferation of transformed cells, it contributes to organismal aging. Recently, senescence has been proposed to support other biological processes such as development and tissue repair. A sharp definition of what a senescent cell is still lacking since we do not have in depth understanding of mechanisms that induce cellular senescence. In addition, senescent cells are heterogeneous, in that not all of them express the same genes and present the same phenotype.Therapeutic applications of mesenchymal stem cells (MSCs) for treating various diseases have increased in recent years. To ensure that treatment is effective, an adequate MSC dosage should be determined before these cells are used for therapeutic purposes. To obtain a sufficient number of cells for therapeutic applications, MSCs must be expanded in long-term cell culture, which inevitably triggers cellular senescence. Thus, the identification of markers for evaluating the status of MSC senescence during long-term culture may enhance the success of MSC-based therapy. This calls for the investigation of the mechanisms of senescence and the development of efficient means to reverse it.

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