Living for a while in a new environment can have a big effect on how you dress, talk, and act. Just listen to Madonna’s British accent. Likewise, taking bone marrow mesenchymal stem cells (BM-MSCs) out of the body and into the in vitro cell-culture environment can change them—but not necessarily for the better.
In order to capitalize on all the wonderful traits and potential stem cells have, researchers need to be able to propagate them without any unwanted side effects. Easier said than done.
Recently, researchers from Italy noted that when BM-MSCs are expanded long-term in vitro, their DNA methylation changes, and they start slowing down and aging. Hey it happens to the best of us, but that could mean challenges for therapies that use these cells.
Mouse and rat BM-MSCs can get weird in vitro, spontaneously transforming and having unstable chromosome counts. But the data for human BM-MSCs are conflicting.
To address this issue, the Italian team analyzed hBM-MSCs from healthy human donors at different passages. Here’s what they found:
- In general, the chromosomes of hBM-MSCs were stable.
- Telomeres were shorter at late passages compared with early ones.
- Cells at late passages also didn’t divide as often as those at early passages.
- CpG island methylation decreased significantly in the cells after long culture periods.
- In a GO analysis, they saw that genes whose promoters had a significant methylation change from methylated to demethylated during in vitro culturing were in the “cell signaling” and “apoptosis and cell death” groups.
The team says that the hBM-MSCs are undergoing “replicative senescence” and aging after long-term culturing. Replicative senescence is a program in which normal somatic cells reach a point at which they stop dividing and have a reduced differentiation potential.
“Our data indicate that long-term culture severely affects the characteristics of hBM-MSCs,” they say. Therefore, they urge caution when using these cells in clinical therapies.
Read all the details at Stem Cell Research & Therapy, November 2012.