Friday, September 27, 2013

Mimicking Morphogenesis in the Lab

Morphogenesis is the name given to the intricate process through which complex organs and tissues are created during the development of the fetus in-utero.  With the stunning and rapid advances made in the areas of biochemistry, molecular biology and genetics especially in regard to stem cells – stem cells are the pluripotent cells that have the inherent capacity to differentiate into a wide variety of specialized tissue cells -, a significant amount of information has been accumulated regarding the molecular mechanisms behind this process. 
In fact, there have been many recent examples of stem cells that have been induced to initiate morphogenesis in a laboratory setting (in vitro).  These studies have been outlined in a review article by Drs. Toshiro Sato and Hans Clevers from the Department of Gastroenterology at the Keio University School of Medicine in Tokyo, Japan that appeared in the journal Science, Vol. 340. June, 2013.  The example the reviewers cite came directly from their own efforts.  In their studies, they have successfully initiated morphogenesis in the laboratory in three-dimensional human cell cultures that resulted in the elaboration of what they refer to as, “Mini-Guts.”

One of the reasons they chose the small intestine as their in vitro model is because this organ has a higher self-renewal rate than any other mammalian tissue.  In fact, all the cells within the small intestine are renewed within five days.  The reason for this remarkable rate is due to the activity of a particular stem cell.  This stem cell type possesses a unique protein receptor on its surface, Lgr5, that binds preferentially with R-spondins a type of protein essential to the process of morphogenesis.  These Lgr5+ cells differentiate into a host of cell types that constitute a healthy and functional small intestine.  In addition, these Lgr5+ cells persist throughout the entire life of the organism.

To accomplish the successful in vitro production of mini-guts- epithelial organoids - that retain the identity and properties of the original tissue, the investigators used  Matrigel that is, in fact, a laminin and collagen-rich matrix that simulates the structural components of the basal lamina of the small intestine.  Additional factors and components that represent the minimal requirements for stem cell growth were also added to this matrix.

This impressive accomplishment has profound implications for the study of disease processes.  For example, it is now feasible to use this same methodology to produce mini-guts from cells derived from patients with adenomas and colorectal cancers.  These organoids could then be studied alongside of organoids derived from normal tissue.   Such studies could prove invaluable in understanding and delineating the etiology of these illnesses. 

No comments:

Post a Comment