Stem Cell Dormancy Enables Them to Remain Viable Days After Death

A collaboration of several researchers from French Institutions has demonstrated that humans and mouse stem cells have the ability to become dormant when their environment becomes hostile, including several days after the death of the organism. This ability to significantly reduce metabolic activity enables them to preserve their potential for cellular division, even a long time after death. Once isolated from the cadaver, the stem cells retain their healing abilities. This discovery could be the beginning of new therapeutic avenues for treating numerous diseases.

Skeletal muscle stem cells have the ability to survive for seventeen days in humans and sixteen days in mice, after death. This discovery was made by researchers from the Institut Pasteur, the Université de Versailles Saint-Quentin-en-Yvelines, the Paris Public Hospital Network (AP-HP), and the CNRS under the direction of Professor Fabrice Chrétien, in collaboration with a team led by Professor Shahragim Tajbakhsh. These laboratories showed that once the stem cells from the cadavers were grown in culture, they retained their capacity to differentiate into perfectly functioning muscle cells.

Once they made this surprising discovery, the next step was to determine precisely how these cells survive such adverse conditions. As it turns out, the stem cells enter a deeper state of sleep (quiescence), and this drastically lowers their metabolism. This so-called “dormant” state results from stripping the functional structures of the cell to their bare minimum. For example, these cells have fewer mitochondria (cellular power plants using oxygen to produce energy in cells) and diminished stores of energy.

Fabrice Chrétien explained it this way: “We can compare this to pathological conditions where cells are severely deficient in resources, before regaining a normal cell cycle for regenerating damaged tissues and organs. When muscle is in the acute phase of a lesion, the distribution of oxygen is highly disrupted. We have even observed that muscle stem cells in anoxia (totally deprived of oxygen) at 4°C have a better survival rate than those regularly exposed to ambient levels of oxygen.”

Chrétien’s team wondered if other cell types showed similar capacities. Once again, the results were surprising. Stem cells from bone marrow where blood remained viable for four days after death in mice. More importantly, they retained their ability to reconstitute tissue after a bone marrow transplant.

This discovery could form the basis of a new source, and more importantly new methods of conservation, for those stem cells used to treat different conditions. For example, leukemia treatments require a bone marrow transplant to restore those blood and immune cells that were destroyed by chemotherapy and radiation. By harvesting stem cells from the bone marrow of consenting donors after death, doctors could address to some extent, the shortage of tissues and cells. Although highly promising, this approach in the realm of cellular therapy still requires more testing and validation before it can be used in clinical applications. However, it paves the way to investigate the viability of stem cells from all tissues and organs post-mortem.