Characterization of Naked Mole-Rat Mesenchymal Stromal Cells: Comparison with Long- and Short-Lived Mammals

Mesenchymal stem and stromal cells (MSCs) show therapeutic potential by facilitating tissue repair.Here, we describe the isolation and initial characterization of MSCs from the longest-lived rodent, the naked mole rat (NMR).NMR MSCs display the CD90/THY1 surface marker characteristic of human and mouse MSCs.The trilineage differentiation capacity of NMR MSCs revealed a bias toward osteogenic differentiation and limited adipogenic potential.Upon passaging in culture, NMR MSCs enter a senescence(definition)-like state characterized by growth arrest, senescent morphology, diminished CD90/THY1, and activated tumor suppressive signaling.The presence of a senescence-like state makes NMR MSCs more similar to human MSCs than to mouse MSCs.However, unlike human MSCs that do not spontaneously immortalize, NMR MSCs eventually give rise to immortalized, rapidly proliferating clones.Unique gene expression profiles of NMR MSCs compared to human and mouse counterparts showed the absence of CXCL12 production, low levels of DNA methylases, and high levels of Sirtuins 1/2/3/6, raising intriguing questions about their contributions to the NMR's remarkable longevity.In summary, our study identified unique features of NMR MSCs, offering insights into a potentially therapeutically relevant stem cell population in a long-lived species.Further studies are crucial to uncover the underlying molecular mechanisms and their implications for human health and aging.