Dormancy of stem cells enables them to remain viable many days after death
15 June 2012
Stem cells can adopt a dormant state when their environment becomes hostile, including several days after death. This ability, observed both in humans and mice, to significantly reduce metabolic activity, allows stem cells to preserve their potential for cellular division, even after extended periods post mortem. This discovery by a team of researchers from the Institut Pasteur, the Université de Versailles Saint-Quentin-en-Yvelines, the Paris Public Hospital Network (AP-HP), and CNRS, under the supervision of Fabrice Chrétien and in collaboration with Shahragim Tajbakhsh, could open new therapeutic avenues for the treatment of numerous diseases.
Once isolated, stem cells could indeed be used to repair damaged organs or tissues. This study is published today in the journal Nature Communications.
Remarkably, skeletal muscle stem cells can survive post mortem, for as long as seventeen days in humans and sixteen days in mice, well beyond the previously-estimated 1-2 day period. In addition, the scientists have succeeded in demonstrating that these stem cells, once placed back in culture, retain their capacity to differentiate into perfectly functioning muscle cells.
In light of this astonishing result, the researchers then sought to characterise these cells to understand how they survive in such adverse conditions. They observed that these cells enter a deeper state of quiescence, drastically lowering their metabolism. This so-called "dormant" state is a result of cellular organisation stripped to the bare minimum: fewer mitochondria (cellular power plants using oxygen to produce energy in cells) and reduced stores of energy.
''We can compare this to pathological conditions where cells severely lack resources, before regaining a normal cell cycle for regenerating damaged tissues and organs," explains Fabrice Chrétien. When a muscle lesion is in the acute phase, oxygen distribution is highly disrupted. We have even observed that muscle stem cells in anoxia (i.e. totally deprived of oxygen) at 4°C display a better survival rate than those regularly exposed to ambient oxygen levels.''
Fabrice Chrétien's team then examined whether these results were consistent with other cell types. Tests were then performed on stem cells taken from bone marrow, where blood cells are produced. These cells remained viable for four days post mortem in mice models, and more importantly, they retained their capacity 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 stem cells used to treat a number of pathologies. This is the case for leukemia, for example, which requires a bone marrow transplant to restore a patient's blood and immune cells destroyed by chemotherapy and radiation.
By harvesting stem cells from the bone marrow of consenting donors post mortem, doctors could, to a certain extent, address the shortage of tissues and cells. Although highly promising, this approach in the field of cellular therapy still requires further testing and validation before it can be used in clinical applications. Nevertheless, it paves the way for investigating the viability of stem cells from all tissues and organs post mortem.