Stem cells supporting other stem cells

Abstract

Adult stem cell therapies are increasingly prevalent for the treatment of damaged or diseased tissues, but most of the improvements observed to date are attributed to the ability of stem cells to produce paracrine factors that have a trophic effect on existing tissue cells, improving their functional capacity. It is now clear that this ability to produce trophic factors is a normal and necessary function for some stem cell populations. In vivo adult stem cells are thought to self-renew due to local signals from the microenvironment where they live, the niche. Several niches have now been identified which harbor multiple stem cell populations. In three of these niches - the Drosophila testis, the bulge of the mammalian hair follicle, and the mammalian bone marrow - one type of stem cell has been found to produce factors that contribute to the maintenance of a second stem cell population in the shared niche. In this review, I will examine the architecture of these three niches and discuss the molecular signals involved. Together, these examples establish a new paradigm for stem cell behavior, that stem cells can promote the maintenance of other stem cells.

Keywords: Drosophila stem cells; germline stem cell; hair follicle stem cell; hematopoietic stem cells; self-renewal pathways; stem cell niche; stem cell therapy.

FIGURE 1

Tissue architecture of three stem cell niches. (A) In the Drosophila testis niche, two stem cell populations, the GSCs and CySCs, intermingle around a cluster of cells called the hub. When the stem cell populations divide, daughters that move away from the hub differentiate, and the differentiating germ cells, which begin to undergo TA, become encysted by the differentiating cyst cells. In this niche, the CySCs produce signals promoting the self-renewal of neighboring GSCs. (B) In the mammalian hair follicle, the bulge and sHG HFSCs reside next to the dermal papilla during telogen, and the MlSC intermingle with the HFSCs. During anagen, the HFSCs and MlSCs divide to produce matrix cells and melanocytes, respectively, which cluster around the dermal papilla and contribute to growth of the new hair. The HFSCs provide molecular signals a different stages of the hair follicle cycle which regulate the behavior of the MlSCs. (C) In the mammalian bone marrow, HSCs have been identified next to sinusoids (blood vessels) and next to the endosteum (osteoblasts). MsSCs, which are innervated by the sympathetic nervous system, cluster around the sinusoids, and are required for HSC maintenance. Other cell populations with reported contributions in this niche are the endothelial cells, macrophages, osteoclasts, and other perivascular stromal cells.