Abstract
Mesenchymal stromal cells (MSC) are currently tested in a large number of clinical trials and raise high hope in regenerative medicine. These cells have to be expanded in vitro before transplantation and several studies demonstrated that long-term culture evokes continuous changes in MSC: proliferation rate decays, the cell size increases, differentiation potential is affected, chromosomal instabilities may arise and molecular changes are acquired. Long-term culture of cell preparations might also have therapeutic consequences, although this has hardly been addressed in ongoing trials so far. Reliable therapeutic regimens necessitate quality control of cellular products. This research perspective summarizes available methods to track cellular aging of MSC. We have demonstrated that gene expression changes and epigenetic modifications are continuously acquired during replicative senescence. Molecular analysis of a suitable panel of genes might provide a robust tool to assess efficiency and safety of long-term expansion.
Highlights
There is growing interest in transplantation of ex vivo amplified cell preparations for various therapeutic applications
Mesenchymal stromal cells (MSC) are currently tested in a large number of clinical trials and raise high hope in regenerative medicine. These cells have to be expanded in vitro before transplantation and several studies demonstrated that long‐term culture evokes continuous changes in MSC: proliferation rate decays, the cell size increases, differentiation potential is affected, chromosomal instabilities may arise and molecular changes are acquired
We have demonstrated that gene expression changes [1] and epigenetic modifications [2] are continuously acquired during replicative senescence
Summary
There is growing interest in transplantation of ex vivo amplified cell preparations for various therapeutic applications. The use of MSC as cellular therapeutics necessitates standardized isolation and reliable quality control of cell preparations. We have demonstrated, that long-term culture is associated with continuous changes in the global gene expression profile [1] (Figure 1).
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