Cellular Senescence in Mesenchymal Stem Cells
Cellular senescence is a cause of aging. Cells become senescent in response to a variety of circumstances: damage, a toxic environment, reaching the Hayflick limit on replication, and so forth. In all cell populations, older individuals exhibit increasing numbers of senescent cells, perhaps largely due to the progressive decline of the immune system and its growing failure to clear out unwanted or harmful cells. Lingering senescent cells secrete a potent mix of signals that rouse the immune system into a state of chronic inflammation, and degrade tissue function and structure. The more of them there are, the worse the outcome.
Mesenchymal stem cells (MSCs) are located in specific areas of tissues, called "niches", and are characterized as being in a state of relative quietness, from which they can exit under the proper conditions to obtain the proliferative potential necessary for tissue regeneration. MSCs have sustained interest among researchers by contributing to tissue homeostasis and modulating inflammatory response, all activities accomplished primarily by the secretion of cytokines and growth factors, because their paracrine action is the main mechanism explaining their effects, regardless of source.
Senescence is defined as a mechanism for limiting the regenerative potential of stem cells. It is now evident that senescent cells secrete dozens of molecules, for which the terms "senescence-associated secretory phenotype (SASP)" and "senescence-messaging secretome (SMS) factors" have been proposed. The secreted factors contribute to cellular proliferative arrest through autocrine/paracrine pathways as well as in vivo and in vitro. SMS factors released by senescent cells play a key role in cellular senescence and physiological aging by activation of cytoplasmic signalling circuitry.
The population of mesenchymal stem cells, also known as mesenchymal stromal cells, contributes directly to the homeostatic maintenance of organs; hence, their senescence could be very deleterious for human bodily functions. The milestone in MSC investigation will be discovering senescence markers to determine the quality of the in vitro cells for cell-based therapies. Researchers have proposed TRAIL receptor CD264 as the first cellular senescence mesenchymal marker in bone marrow-derived MSCs, because it has the same expression profile of p21 during culture passage.