Cell death

From FETAL PRECURSOR CELL TRANSPLANTATION (FPCT)
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Eukaryotic cells can disappear in two different ways:

1/ necrosis as a result of damage, i.e. induced death;

2/ apoptosis, i.e. programmed cell death. Apoptosis does not lead to cell membrane damage and leak of intracellular contents, that triggers an induction of inflammatory response. Apoptosis is a physiological way of maintaining of homeostasis and tissue regeneration.


1/ Necrotic cell death:


Survival of cells depends upon maintenance of normal intracellular environment. Lack of oxygen and insufficient production of ATP are two key factors that disrupt the intracellular milieu.


Insufficient supply of oxygen causes switching of energetic metabolism to anaerobic glycolysis. Production of lactic acid, dissociating into lactate and H+, causes intracytoplasmatic acidosis with subsequent interference with function of intracellular enzymes, whereby glycolysis slows down, and thereby the last source of ATP dries out.


Inadequate energy supply exposes the cell to oxidative damage because all protective mechanisms against 02-radicals depend upon ATP. There is a threat of cell membrane destruction due to lipid peroxidation with the release of intracellular macromolecules into the extracellular space. Since immune system is normally not exposed to intracellular macromolecules, and thereby no immunotolerance has ever developed, the immune system is activated, inflammatory reaction takes place, and that leads to further cell damage.


2/ Apoptotic cell death:


Hundred billions of cells are eliminated in our bodies daily and replaced by new daughter cells provided by mitosis. Apoptosis is the programmed cell death regulated by physiologic mechanisms that serve the adaptation of tissues to varying demands, elimination of redundant quantity of cells, as well as the elimination of harmful cells, i.e. cancerous, virus-infected, or immunocompetent cells that turned against ‘self’ antigens.


Pathologically increased apoptosis, not planned by organism, causes excessive elimination of functionally necessary cells, leading to an organ insufficiency. In this way apoptosis can lead to neurodegenerative diseases such as Parkinson’s disease, Alzheimer disease, ALS, transverse myelitis with paralysis, multiple sclerosis, etc., or toxic, ischemic or inflammatory apoptosis of liver cells in liver insufficiency, or Beta-cells of islets of pancreas in IDDM, erythropoietic cells in aplastic anemia or lymphocytes in immunodeficiency, AIDS, etc.


Pathologically decreased apoptosis of virus-infected cells becomes the cause of persistent infections. Cells without apoptosis become cancerous. Decreased apoptosis of immunocompetent cells that turned against ‘self’-antigens become a cause of autoimmune diseases. Insuficient apoptosis leads to disturbances of embryonic development, i.e. syndaktylia.


Replacement of a cell lost by apoptosis is a function of regeneration, and regeneration can be therapeutically stimulated only by fetal precursor cell transplantation.