Tissue stem cells

Most tissues, also in adults, can renew with the help of the tissue stem cells that reside in them.

The activity of tissue stem cells and the pace of tissue renewal varies a lot depending on the tissue. The inside lining of the intestine for example, renews completely approximately in five days when the stem cells divide and produce new cells that replace the old ones. In comparison, the renewal capacity of for example the brain is very limited.

Tissue renewal

Tissue stem cells renew tissues by dividing and differentiating into specialized cells. An example of tissue stem cells are blood stem cells (hematopoietic stem cells) which are found in the bone marrow and produce red and white blood cells and platelets. Another example are intestinal stem cells, which differentiate into both nutrient absorbing cells and cells that secrete hormones or mucus.

Depending on the tissue, the tissue renewing stem cells are either multipotent and can produce many types of specialized cells, or unipotent and can differentiate only into one type of cell. During development, tissues are built up of many types of embryonic cells. In adults, many different types of tissue stem cells take part in maintaining the function of each organ including for example it’s blood supply and support tissues.

Tissue stem cells have to maintain the functions of the tissues that were built during development, despite of many challenges. To replace cells that are damaged and die as a result of normal tissue function, tissue stem cells produce new specialized cells at a relatively constant pace. Blood stem cells and intestinal stem cells for example constantly produce new progeny. In contrast to this, muscle stem cells are normally quiescent and activate only if they receive a signal of muscle injury.    


The stem cell niche

Tissue stem cells are dependent on their surroundings and neighbour cells and in tissues they always work in cooperation with the stem cell niche. For example, intestinal stem cells, which reside in invaginations or crypts of the intestinal epithelium, where they renew the epithelial cells around once a week, are dependent on other cells such as niche cells or stromal cells and on signals from the extracellular matrix. 

The stem cells receive signals from the specialized cells of the stem cell niche and these signals control for example the proliferation and differentiation of the stem cells. The stem cell niche also provides protection and nutrients for the stem cells. Many tissue stem cells are in addition to producing functional cells of the tissue, also able to produce their own niche or support cells and can thus in principle build a new tissue on their own. Because of this self-organizing capacity, tissue stem cells can produce mini-organs or so-called organoids. Organoids are used as tools in tissue renewal research and may possibly in the future enable manufacturing of tissues in the laboratory.   

Plasticity and dedifferentiation

Sometimes tissues are injured for example because of an accident. Wounds of the skin are closed independently of stem cell activity at first to prevent bleeding, but ultimately the skin stem cells renew the wounded skin where possible. The renewal of tissues or damaged structures is however very limited in humans after fetal development. In contrast, for example salamanders can even build new limbs after amputation. This is because tissue renewal in salamanders in not solely dependent on stem cells. Instead, specialized cells can return to a stem cell like state and reactivate cell programs from the developmental stages. This kind of dedifferentiation is rare in humans. Thus, most injuries leave a mark, even if tissue function can be restored.  

The ability of some specialized cells to return to a stem cell state has challenged the long dominating notion of stem cells being on top of a clear and one-directed hierarchy of cells. In tissues, where stem cells divide actively and compete for contacts with the niche, single stem cells can lose their place and thus be forced to differentiate. On the other hand, if part of the stem cells die, for example because of a disease, some specialized cells can dedifferentiate and regain stem cell properties. This is referred to as cell plasticity, or capability to change. The human body can however not for example grow new organs or limbs.

Tissues are also exposed to changes as a result of the functions of other tissues or for example changes in nutrition. Tissues adapt to changed conditions by gradually adjusting the behaviour of the stem cells through a process that can take days or even years. With time, stem cells lose their ability to renew and change the tissues. When damaged stem cells are no longer replaced with new ones, the function of the tissue declines and it gets susceptible to disease. The declined function of tissue stem cells is a normal and critical part of aging.