A stem cell niche is an environment within the body where a specific variety of stem cell is nurtured:

Stem-cell populations are established in 'niches' - specific anatomic locations that regulate how they participate in tissue generation, maintenance and repair. The niche saves stem cells from depletion, while protecting the host from over-exuberant stem-cell proliferation. It constitutes a basic unit of tissue physiology, integrating signals that mediate the balanced response of stem cells to the needs of organisms. Yet the niche may also induce pathologies by imposing aberrant function on stem cells or other targets. The interplay between stem cells and their niche creates the dynamic system necessary for sustaining tissues, and for the ultimate design of stem-cell therapeutics ... The simple location of stem cells is not sufficient to define a niche. The niche must have both anatomic and functional dimensions.

Niches age with the rest of your tissue, and for much the same reasons; an accumulation of a variety of types of cellular and biochemical damage. The machine gathers faults and rust over the years, and gradually moves towards serious failure.

There has been some debate over the past few years as to whether the well-known decline in function of stem cell populations with age occurs because of changes in the stem cells, or because of changes in their niches. It seems that the consensus is presently leaning towards the niche explanation:

Adult stem cells provide the basis for regeneration of aging tissue. Their dual ability for self-renewal and multilineage differentiation is controlled by direct interaction with a specific microenvironment - the so called "stem cell niche".

Hematopoietic stem cells (HSC) reside in the bone marrow. It is still under debate if HSC can rejuvenate infinitively or if they do not possess "true" self-renewal and undergo replicative senescence such as any other somatic cell. Furthermore, the question arises to what extent age-related changes in HSC are due to intrinsic factors or regulated by external stimuli. There is growing evidence, that the stem cell niche is most important for the regulation of cellular aging in adult stem cells.

It is the stem cell niche that (i) maintains HSC in a quiescent state that reduces DNA damage as well as replicative senescence, (ii) protects from radicals and toxic compounds, (iii) regulates cell intrinsic signal cascades and (iv) modulates gene expression and epigenetic modifications in HSC. Thus, the interplay with the stem cell niche controls HSC function including the aging process of the hematopoiesis.

As accumulating age-related damage causes the cells and processes of the niche to malfunction, the stem cells it supports suffer. One consequence of the dominance of the aging niche is the direction taken in order to develop the next generation of stem cell therapies. Clearly it's not enough to gain far better control over stem cells if the damaged niche then sabotages your efforts.

I believe that this will likely see the large and well-funded regenerative medicine industry start down the path of trying to rejuvenate and repair stem cell niches. I don't know when that will start in earnest, but it will be a tremendous opportunity for those of us interested in the success of more general strategies for biochemical repair throughout the body - a chance to apply large-scale funding and a large research community to specific challenges in repairing the damage of aging.

Posted by Reason at May 28, 2008 6:24 PM | TrackBack (0)