How Does Regeneration Take Place?

There are three mechanisms by which tissue can regenerate itself in mammals:

  1)    Compensatory Hyperplasia
 In order for the organism to survive while a damaged liver re-grows, the hepatocytes (liver cells) must be able to continuously divide while maintaining most or all their functions, including blood filtration, metabolism of toxins, and bile secretion.  Scientists are currently trying to understand how and why hepatocytes are capable of this increase in cell production while still maintaining or even increasing their function to compensate for the loss of tissue.

  2) Activation of Resident or Circulating Adult Stem Cells (ASCs)
Adult stem cells are a subset of cells that are capable of self-renewal and can differentiate into many different cell types.  These cells are present throughout an organism’s lifespan and have several features:
          1)    They are self-renewing.  Typically, when ASCs are triggered to divide, they undergo disproportionate division or asymmetric mitosis.  One cell remains an adult stem cell and the other goes on to become whatever cell is needed at that time.  

          2)    ASCs can be picky.  Unlike Embryonic Stem Cells (ECS), ASC are not able to differentiate into just any type of tissue.  The ability of an ASC to develop depends on its stage in life or the tissue that houses it.  The surrounding factors of the ASC will send signals that will influence how the    cell functions.  Examples of tissues that harbor ASCs are skin, liver, bone marrow, and skeletal muscle. 

          3)    Family is everything, at least for an ASC.   ASCs rely on their home, or what scientists call microniches, to maintain their stem cell capabilities.  These microniches create an environment of free and open communication by acting as liaison between the stem cells and the rest of the tissue by sending and receiving soluble and insoluble signals.  The niches are important for three reasons:

1.    They keep the ASCs happy and in a state of “stemness” where the cells can maintain their status as Stem Cell
2.    They keep the ASCs’ feet on the ground, literally.  The connection beweteen the ASCs and their microniche environment is essential for their function.  When scientists mutate genes that disconnect ASCs from their niche, they can no longer remain stem cells.
3.    The microniche helps determine whether a stem cell will divide asymmetrically (division of 1 stem cell into 1 daughter stem cell and 1 daughter cell that is committed to differentiate) or symmetrically (division of 1 adult stem cell into 2 daughter stem cells)

4)    Creation of Stem Cells via Dedifferentiation
Cells that have already developed to their end fate (differentiated cells) are capable of turning back into adult stem cells (dedifferentiation).  These cells give up their current occupation to return back to it’s position as stem cell.  This is seen primarily in low order vertebrates such as fish, lizards, and amphibians.   These organisms are able to regenerate limbs, tails, fins, jaws, parts of the eye, nerves, and intestine. 

5)    Signaling Pathways inside and between cells
At any given time, millions of cells in our body are hard at work, maintaining our daily functions and helping us do all the things we love to do.  Cells work by using signaling pathways to talk to themselves and to other cells within the body.  It is this communication that enables our systems to operate as the giant symphony we know as the human body.  For example, the endocrine system is spread over 8 different organs throughout the body that must communicate with each other on a constant basis.  These organs use signaling pathways throughout the bloodstream to interact and function as an entire system.  All stem cells use both internal and external signal transduction pathways in order to interact with each other as well as other cells in their microniche.  These pathways will regulate division patterns of the stem cells.