Résumé
In most western countries, the average age of the population increases, raising a series of challenges to achieve healthy aging. The risk of bone frailty and fractures is significantly increased with aging, altering the quality of life for elderly people and constituting a major public health problem. Declining bone turnover results from progressive degenerative processes observed in the bone-marrow. These include loss of regenerative potential, low grade inflammatory microenvironment due to senescence associated secretory phenotype (SASP), epigenetic modifications and a myeloid differentiation bias. Bone-marrow mesenchymal stromal cells (BM-MSCs) are adult progenitor cells contributing both to hematopoietic stem cell niche and bone tissue repair functions thanks to multipotence capacities and paracrine functions. We developed an in vitro model of 3D spheroids originated from human BM-MSCs enriched in stress-induced senescent BM-MSCs to study how senescence of BM-MSC subtypes impact their progenitor functions and bone microenvironment through SASP secretion.