Stem cell niche
Stem cell niche
Stem cells in animal tissues are often located and controlled by special tissue microenvironments known as niches. Stem cells are emerging as one of the fundamental underpinnings of tissue biology. They allow blood, bone, gametes, epithelia, nervous system, muscle, and myriad other tissues to be replenished by fresh cells throughout life. Additional stem cells lie dormant, but can be activated at particular life cycle stages, or following injury.
The impairment in tissue homeostasis, repair, and regeneration with age is largely attributed to a decline in the ability of resident stem cells in individual tissues to efficiently and effectively give rise to new parenchymal cells. To understand the processes that contribute to declining stem cell function with age, it would be necessary to identify the factors that influence stem cell activity. Importantly, the efficiency with which stem cells replace tissue is a combinatorial function of cell-extrinsic and cell-intrinsic factors that govern stem cell activity. Support cells within the niche influence stem cell function via direct interaction of membrane proteins present on the apposing cells, and also by the secretion of soluble factors and extracellular matrix components that bind to integral proteins expressed by stem cells and modulate their behavior. For instance, in the bone marrow, the resident osteoblasts secrete the matrix sialoprotein, osteopontin, that binds to receptors, such as CD44, α4β1integrin and α5β1 integrin, expressed on the hematopoietic stem cells. The absence of osteopontin results in an increase in the number of stem cells. In the skin, extracellular matrix proteins secreted by support cells bind to β1integrin expressed on matrix stem cells and regulate their proliferation.
The reduced capacity to regenerate injured tissues or organs and an increased propensity to infections and cancers are probably the most prominent features of aging. Adult stem cells such as hematopoietic stem cells (HSC) or mesenchymal stem cells (MSC) assure lifelong regeneration of adult tissues (e.g. all different types of blood cells or bone, fat and cartilage, respectively). If the rejuvenating effect of stem cells was perfect, senescent cells could be replaced indefinitely. Aging is not only associated with functional alterations of HSC but also with an altered microenvironment that is required for hematopoietic differentiation. HSC from young mice had a reduced differentiation potential towards lymphocyte phenotype in aged than in young recipients. On the other hand, HSC from aged mice also had a reduced lymphoid differentiation potential in young mice. These studies indicate that aging is associated with HSC intrinsic changes as well as with changes in the microenvironment. Taken together, the stem cell niche undergoes extensive changes during the lifetime of the organism and these might play an important role for external control of stem cell aging.