Culturing Cell Lines and Stimulating Stem Cells to Differentiate

Cell culture  is a term that  refers to the growth  and maintenance of cells in a controlled  environment out- side of an organism.  A successful stem cell culture  is one that  keeps the cells healthy,  dividing, and unspe- cialized. The culturing  of stem cells is the first step in establishing a stem cell line—a propagating collection of genetically identical  cells. Cell lines are important because they provide a long-term  supply of multiply- ing  cells  that   can  be  shared  among   scientists  for research and therapy development. The National Academies report Stem Cells and the Future of Regenerative  Medicine  (2001) described some of the challenges  of maintaining cell lines: “Over  time,  all cell lines…change, typically accumulating harmful genetic mutations. There is no reason to expect stem cell lines to behave  differently.  While there  is much that can be learned using existing stem cell lines…such concerns  necessitate  continued   monitoring of  these cells as well as the development  of new stem cell lines in the future.”


Once they have established  a stable stem cell line, sci- entists start the process of causing the stem cells to dif- ferentiate into specialized cell types. The cellular environment in which stem cells naturally  reside pro- vides scientists  with  clues about  how  to make them differentiate in a culture dish. For example, in  the  bone  marrow,   where  blood  stem  cells reside, bone cells send physical and chemical sig- nals that tell the blood stem cells when to differ- entiate.  Scientists  are  just  beginning  to  under- stand  these signals and have developed  ways to mimic the natural  processes in cell cultures. Usually,  the technology  involves adding  certain proteins to the cell culture  and,  in some cases, introducing specific genes into the stem cells.

It will be essential  that  scientists  are  sure  that stem  cells have  fully  differentiated before  they can use them for medical applications. If completely  undifferentiated stem  cells (such  as embryonic stem cells) are implanted  directly into an  organism,  they  can  cause  a  type  of  tumor called a teratoma,  which scientists have observed in  experiments   using   mice.  Semi-specialized adult  stem cells and  differentiated cells derived from embryonic  stem cells are unlikely to cause teratomas.