Cellular senescence occurs in response to stress, damage, and cells hitting the Hayflick limit on replication. Senescent cells cease replication, and begin to secrete a pro-inflammatory, pro-growth mix of signals. In cell cultures, senescence is a common phenomenon. Researchers are beginning to realize that the presence versus absence of senescent cells in culture may explain a sizable fraction of the variation in outcomes resulting from stem cell therapies. Slightly different methodologies of production of stem cells for transplantation may result in sizable differences in the proportion of those cells that are senescent, and thus the ability of the treatment to produce benefits to a patient.
Another consideration is the age of the donor. In today’s open access paper, researchers demonstrate that mesenchymal stem cells taken from bone marrow are more senescent in culture and less capable of inducing regeneration following transplantation when the source is older mice versus younger mice. This problem can be mostly fixed by applying the senolytic combination of dasatinib and quercetin briefly to cultured cells, destroying many of the senescent cells, prior to transplantion. Senolytic treatment of cells to be used in cell
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