Researchers here demonstrate a more efficient path to the production of large numbers of patient-matched immune cells. Delivering large numbers of immune cells via infusion on a regular basis may prove to be a useful treatment for older individuals suffering the characteristic immune dsyfunction that accompanies aging, a near-term way to restore vital immune functions ranging from clearance of unwanted cells to defense against pathogens, a stop-gap to be used until the underlying causes of immune aging can be reversed. The cost of generating the necessary cells is a big determinant of whether or not a therapy is developed for widespread use, however.
Though immune therapy and regenerative medicine are promising areas of research for future medical therapies, they are limited today by the difficulty of creating stem cells, and scientists around the world are searching for ways to create somatic stem cells in the easiest way possible. Researchers have now found that in immune cells, simply blocking a transcription factor that leads to differentiation is sufficient to keep cells in a multipotent stem cell-like state where they can continue to proliferate and can later differentiate into various cell types. Efforts in the past to create stem cells have typically involved finding ways to take target cells and "dedifferentiate" them into multipotent cells, but this is typically a painstaking process.
The team took mouse hematopoetic progenitor cells - cells that give rise to white blood cells - and modified them to overexpress a protein called Id3. Id3 inhibits the expression of E-proteins, which are involved in differentiation in somatic cells. They then placed the cells into culture conditions containing certain cytokines, and instead of differentiating into B-cells, the cells continued to divide as stem cells. When placed in a culture that did not contain those cytokines, the cells differentiated into various immune cells. To test whether the cells would maintain their multipotency in living animals, the researchers transplanted them into mice whose white blood cells had been depleted, and showed that the new cells could expand and differentiate into various types of white blood cells.
To explore the potential for application, the group then attempted a similar experiment using human blood stem cells taken from umbilical cords, which they transfected with a vector encoding human Id3. They found that like the mouse cells, these human cells could be maintained in a dividing state and then prompted to differentiate by changing the conditions. "This is both a useful tool for giving us a better understanding of the genetic and epigenetic program controlling the self-renewal of stem cells, and on a practical side, it could allow us to inexpensively produce large numbers of immune cells, which could then be used for regenerative medicine or immune therapy."