Disease-in-a-Dish – Another Application of Stem Cell Research

Stem cells have the capacity to be transformed into any specialized body cells under the right conditions.  This may seem very surprising, but there is an explanation that has at its roots in the nature of the genetic structure of living cells.  All cells in the human body, regardless of their structure and function, have the identical set of genes (genome).  If the genes determine the structure and function of cells, what, therefore, establishes the various unique and diverse tissue cell types such as liver, kidney, skin, etc.  The answer lies in what genes are expressed, turned on and what genes are not expressed, turned off.  The process of selectively turning genes on or off to produce specialized cell types is referred to as differentiation.  Stem cells are pluripotent – they are capable of becoming any specialized cell type under the appropriate conditions.

A considerable controversy erupted over the use of stem cells due to the fact that the source of these cells was from human embryos – so-called embryonic stem cells.  However, a new class of stem cells has been developed that are derived from the use of ordinary tissue cells treated with a cocktail of specific initializing factors that transform these cells to stem cells, so-called induced pluripotent stem cells (iPS) that have been shown to exhibit the same capacity as embryo-derived cells.

The following is a description of a direct application that utilizes iPS in a very interesting and potentially useful way.  Doctor K. Eggan and his colleagues from the Harvard Stem Cell Institute (HSCI) collected skin cells from two patients suffering from amyotrophic lateral sclerosis (ALS).  ALS is a degenerative disease of the nerve cells in the brain and spinal cord that control voluntary muscle movement also known as Lou Gehrig's disease.  These fibroblast cells were subsequently grown in culture and treated with the appropriate regulator genes to reprogram the cells to become iPS cells and thereby pluripotent  in behavior.  These iPS cells tend to clump into what is referred to as "embryoid bodies" and to these clumps were added retinoic acid and a compound that is known to accelerate cell division.  The result of the addition of these added factors was to successfully transform these embryoid bodies into motor neurons.

Since these newly derived nerve cells originated from patients with ALS, they retain all of the genetic properties and characteristics of the disease.  This affords an excellent opportunity to test these cells with drugs that may have potential therapeutic value for ALS patients. 

This  approach as outlined above is referred to as "disease-in-a-dish" and is an expansion of the pioneering efforts of Doctor Yamanaka from Japan.   It offers great promise in the study of such intractable diseases as ALS.