A case report: bone marrow mesenchymal stem cells from a Rett syndrome patient are prone to senescence and show a lower degree of apoptosis.

Rett syndrome (RTT) is one of the most common genetic diseases responsible for a progressive disabling neurodevelopmental disorder. Mutations in the MeCP2 gene were identified in the great majority of RTT patients. MeCP2 protein binds to methylated DNA and produces changes in chromatin structure. This is a key event in regulation of gene expression. It has been suggested that MeCP2 might be important for neuronal development. Moreover, the frequent occurrence of osteoporosis and scoliosis in RTT patients suggests impaired bone formation and/or remodeling. Mesenchymal stem cells (MSCs) can differentiate as mesodermal cells such as bone, cartilage cells, and adipocytes. MSCs have been shown to possess great somatic plasticity; in fact, they can differentiate as neurons and astrocytes. We studied RTT patients' MSCs because they are progenitors of osteocytes, and it has been suggested that RTT patients' osteogenesis could be impaired. Moreover, MSCs might represent a useful model for the study of neurogenesis. MSCs from RTT patient showed precocious signs of senescence in a comparison with the MSCs of healthy-patient control groups. This was in agreement with the reduced gene-expression in the control of stem cell self-renewal and upregulation of lineage specific genes, such as those involved in osteogenesis and neural development. Control groups enabled us to observe a lower degree of apoptosis in RTT patient cells. This means that aberrant stem/progenitor cells, instead of being eliminated, can survive and become senescent. Our research provides a new insight into RTT syndrome. Senescence phenomena could be involved in triggering RTT syndrome-associated diseases.