Stem cell niche

Stem cell niche is a phrase loosely used in the scientific community to describe the microenvironment in which stem cells are found, which interacts with stem cells to regulate stem cell fate. The word 'niche' can be in reference to the in vivo or in vitro stem cell microenvironment. During embryonic development, various niche factors act on embryonic stem cells to alter gene expression, and induce their proliferation or differentiation for the development of the fetus. Within the human body, stem cell niches maintain adult stem cells in a quiescent state, but after tissue injury, the surrounding microenvironment actively signals to stem cells to either promote self renewal or differentiation to form new tissues. Several factors are important to regulate stem cell characteristics within the niche: cell-cell interactions between stem cells, as well as interactons between stem cells and neighbouring differentiated cells, interactions between stem cells and adhesion molecules, extracellular matrix components, the oxygen tension, growth factors, cytokines, and physiochemical nature of the environment including the pH, ionic strength (eg Ca 2+ concentration, metabolites like ATP are also important. The stem cells and niche may induce each other during development and reciprocally signal to maintain each other during adulthood.

Scientists are studying the various components of the niche and trying to replicate the in vivo niche conditions in vitro. This is because for regenerative therapies, cell proliferation and differentiation must be controlled in flasks or plates, so that sufficient quanitity of the proper cell type are produced prior to being introduced back into the patient for therapy.

Human embryonic stem cells are often grown in fibroblastic growth factor-2 containing, fetal bovine serum supplemented media. They are grown on a feeder layer of cells, which is believed to be supportive in maintaining the pluripotent characteristics of embryonic stem cells. However, even these conditions may not truly mimick in vivo niche conditions.

Adult stem cells remain in an undifferentiated state throughout adult life. However, when they are cultured in vitro, they often undergo an 'aging' process in which their morphology is changed and their proliferative capacity is decreased. It is believed that currect culturing conditions of adult stem cells needs to be improved so that adult stem cells can maintain their "stemness" over time.

A Nature Insight review defines niche as follows: ""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""

- David T. Scadden

History
Though the concept of stem cell niche was prevailing in vertebrates, the first characterization of stem cell niche in vivo was worked out in Drosophila germinal development.

Drosophila gonads
A. Ovary

In the Drosophila ovary the niche consists of terminal filament cells and cap cells which support two adjacent stem cell populations: the germline stem cells and escort stem cells. The somatic follicle stem cells are maintained in an acellular niche, apparently by long-range signals from the terminal filament and cap cells.

B. Testis

In the Drosophila testis the niche consists of the hub cells which support two adjacent stem cell populations: the germline stem cells and the somatic cyst progenitor cells.

ES Cell niche
For vertebrate embryonic stem cells in vivo the niche is formed by the trophoblasts.

A. Hematopoietic stem cell niche
Vertebrate hematopoietic stem cells niche in the bone marrow is formed by cells subendoosteal osteoblasts, sinusoidal endothelial cells and bone marrow stromal (also sometimes called reticular) cells which includes a mix of fibroblastoid, monocytic and adipocytic cells.

B. Hair follicle stem cell niche
The bulge area at the junction of arectores pili muscle to the hair follicle seath has been shown to host the skin stem cells with maximum span of developmental potential. There cells are maintained by signaling in concert with niche cells - signals include paracrine (eg sohic hedgehog), autocrine and juxtacrine signals.

C. Intestinal stem cell niche
The subepithelial fibroblast/myofibroblast network which surround the intestinal crypts constitute the niche.