Question: Does anyone know much about stem cell use in therapeutic cloning? One of my students was asking how a group of stem cells can be cultured to differentiate into one specific cell type over another. How do scientists control what the cells will become?

Alena Pance answered on 31 Dec 2019:

This is indeed the basis of much of the work we do with stem cells. Though they are pluripotent, which means they have the potential to differentiate into a variety of cell types, the differentiation is not at all a straight forward process. We have quite complex protocols to achieve this in the lab. Some are driven by providing signalling molecules in the medium, called cytokines that ‘tell’ the cell what to do, ie what genes to switch on in order to become the cell type we are after. Another way to do it, that we have worked on quite a lot is to introduce factors into the stem cells that will directly switch on the needed genes. These are called transcription factors and their function is precisely to regulate gene expression, so finding those that are crucial for a particular cell type is the first step for this process.
For example our protocol to generate red blood cells from stem cells has several stages during which the cells are exposed to different sets of cytokines and the whole process takes around a month.
In terms of therapeutic applications, it is very important that all the cells differentiate in the same way and to the same extent. This depends very much on the cell type being generated but in general, is really difficult. In general, we always get a mixture of cells that are at different stages of differentiation and some are even different cell types. So the culture has to be purified either by eliminating the unwanted cells or by selecting the ones we want. This depends on the application though because sometimes putting the cells in their microenvironment in the body drives them to differentiate correctly. For example, the oldest cell therapy we have: bone marrow transplant, relies on introducing haematopoietic stem cells into the recipient, which will repopulate the bone marrow and generate all the cell types of the blood.