Introduction to Stem Cells

Human tissues

The human body consists of about 35 billion  (35,000,000,000,000) cells.  To perform diverse functions in a multicellular organism the cells are highly specialized in different tissues. It is estimated that the entire complement of human tissues contains approximately  two hundred terminally differentiated cell types. Many cells which are highly specialized have lost the ability to divide and their life-span is shortened.  For example enterocytes (intestinal cells specialized for absorption of nutrients) are alive for 4-6 days and red blood cells remain functional for 120 days. Even those differentiated cells that have not lost the ability to divide can enter the cell cycle only 50-60 times (known as the Hayflick limit). To maintain the structure and function of tissues composed of cells that die or have a limit in their mitotic activity, it is crucial to replenish the pool of lost cells. This task is performed by stem cells. 

Stem cells
In contrast to specialized (i.e. differentiated) cells, stem cells are preserved in tissues in the undifferentiated state. This means they do not bear any features typical to differentiated cells, rather they have the characteristics of primitive cells. This explains why stem cells were overlooked in adult tissues for so many decades. Their presence was eventuallly recognized because of their behaviour that is so different from specialized cells. Stem cells can divide indefinitely and generate copies of themselves (stem cell self-renewal) and differentiated cells at the same time. The easiest way that explains this behaviour is by asymmetric cellular division . A division of the mother cell gives rise to two daughter cells that are not equal. One new cell is identical to the original mother cell and occupies its original site (this is the stem cell) whereas the second daughter cell (progenitor cell) that differs slightly is pushed outside. The progenitor cells produce differentiated cells in the tissue.  

Where do stem cells come from?
All diverse cells in multicellular organisms derive from the fertilized egg (zygote). The zygote cannot self-renew and for this reason is not considered to be a stem cell although its differentiation potential is totipotent. After initial divisions (cleavage), the morula arises and its cells (blastomeres) already bear the features of stem cells which are also totipotent. As the embryo grows, new cells are produced which are more specialized. As a result differentiated potential of younger stem cells becomes narrower and narrower. For example, the stem cells of the inner cell mass in the blastocyst are pluripotent whereas primordia of developing tissues contain tissue-specific stem cells which are usually multipotent. In the course of development, the stem cells divide and produce differentiated cells of the tissue. At early developmental stages the number of stem cells is high but during organ maturation differentiated cells exceed stem cells in number. It is estimated that in adult tissues there is approximately 1 stem cell per 10,000 differentiated cells.