The Bone Marrow Microenvironment is Sensitive to the Stresses of Aging
The open access paper here is a good companion to yesterday's review of what is know of the way in which chronic inflammation disrupts hematopoiesis. Hematopoiesis is the complex process by which hematopoietic stem cells in the bone marrow produce blood and immune cells, vital to the function of the immune system. The immune system becomes overactive in later life, pushed into a constant state of low grade inflammation by the damage of aging and its consequences, such as rising numbers of senescent cells that produce inflammatory signaling. This chronic inflammation causes dysfunction in hematopoiesis, thus further harming immune function.
In the skeletal system, vasculature plays a crucial role in nutrient delivery and maintenance of the resident stem cells and progenitor cells that regulate osteogenesis and hematopoiesis. Bone marrow (BM) harbors stem and progenitor cells of different lineages including hematopoietic and mesenchymal stem cells that differentiate into a variety of mature functional cells, contributing to osteogenesis and hematopoiesis. These stem and progenitor cells reside in specialized local microenvironments within the BM, known as BM niches. BM niches provide crucial signals for stem and progenitor cell survival, quiescence, mobilization, and differentiation. These signals come in the form of soluble factors, cell surface ligands, or cell-to-cell interactions which regulate stem and progenitor cell fates.
The BM microenvironment is highly sensitive to stress. Growing evidence suggests that stress-induced molecular changes of the BM microenvironment disrupt homeostasis. BM endothelial cells (ECs) and their secreted factors, called angiocrine factors, regulate hematopoietic stem and progenitor cell homeostasis and function. Stress associated with aging, inflammation, bone diseases, or bone malignancies can disrupt vascular morphology and angiocrine signaling, with significant impacts on osteogenesis, bone angiogenesis, and hematopoiesis.
The response of the BM microenvironment to stressful conditions and diseases has received increased attention over the past few years. Nevertheless, the knowledge about the effects of stress on the BM microenvironment remains incomplete and is a hot topic of research. This review aims to define the cellular and molecular response of the BM vascular niche to different stresses by comparing the BM vascular niches in homeostasis and under various stress conditions such as aging, inflammation, and malignancy.