Cord Blood-Derived Stem Cells – a New Therapeutic Option for Brain Disorders?
Stem cell technology has the potential to revolutionize medicine, but the revolution has been considerably slower than expected. Government restrictions and ethical dilemmas have put up roadblocks to fast-paced biological research, and even when these roadblocks are absent, controlling the behavior of stem cells (cells that have the ability to form a number of cell types and tissues) in a petri dish has proved tricky to say the least.
In one particular area of stem cell research, however, progress has been steady. Cord blood stem cells can be harvested from the umbilical cord and placenta of a newborn baby and stored for future use, the idea being that they can be used down the road should that baby (or a genetically similar relative) become sick. These stem cells have been used to treat close to 100 blood-based conditions, including several types of leukemia.
One particular challenge has been to force cord blood stem cells to become anything other than a blood cell. This is because stem cells exist in varying degrees of “stemness”; that is they differ in their ability to form different kinds of tissue or cells. For example, blood stem cells are really good at generating all of the different types of blood cells, but do not generate skin cells. However, researchers at the Salk Institute for Biological Studies in collaboration with scientists in Barcelona, Spain, have succeeded in coaxing these stem cells to become neurons, a groundbreaking step in the treatment of traumatic brain injury and other neuronal disorders.
When a stem cell divides, the DNA of one cell retains its stem cell identity. The DNA in the second cell, on the other hand, can assume a different identity. The first step in assuming this identity (known as differentiation) generally involves turning on a master-regulator gene that then controls the activity of another gene and another gene and so on until, for example, the cell becomes a neuron. The key to controlling stem cells, therefore, lies in figuring out how to turn on the master-regulator.
In order to turn cord blood cells into neuronal cells, Alessandra Giorgetti and colleagues first manipulated the cells so that they produced an increased amount of a gene called Sox2. They then cultured the cells and analyzed their genetic behavior. What they found was that these manipulated cells were starting to behave like immature neurons: Sox2 was the master-regulator.
The next challenge was to keep the cells on track so that they finished the job of becoming a neuron. Using special conditions the team managed to get the cells to form mature neurons that both extended long nerve-like projections and responded to electrical stimulation in vitro.
The real test, however, was whether or not these cells repopulate a damaged brain. It is one thing to generate a single cell type, and quite another to induce those cells to form a coherent and functional tissue. Giorgetti and her colleagues therefore took the cord blood-derived neuronal cells and transplanted them into immuno-compromised mice (that could not reject the non-mouse graft) and monitored their progress over a period of three months. They found that indeed the cord blood-derived neurons grew and integrated into the mouse brains, and were capable of limited activity.
While it maybe some time before such a treatment reaches the clinic, this work emphasizes the potential of this type of stem cell. With cord blood banking becoming more and more commonplace, and an expansion of the application of cord blood stem cells beyond the treatment of blood disorders, these malleable cells are fast becoming the stars of stem cell research.
Alessandra Giorgettia, Maria C. N. Marchettob, Mo Lic, Diana Yub, Raffaella Fazzinaa, Yangling Mub, Antonio Adamoa, Ida Paramonova, Julio Castaño Cardosoa, Montserrat Barragan Monasterioa, Cedric Bardyb, Riccardo Cassiani-Ingonia, Guang-Hui Liuc, Fred H. Gageb, & Juan Carlos Izpisua Belmontea (0). Cord blood-derived neuronal cells by ectopic expression of Sox2 and c-Myc PNAS DOI: 10.1073/pnas.1209523109