A group of scientists at the Salk Institute in San Diego transformed umbilical blood cells into cells that look and act a lot like neurons. They call them “neuronal like.” The team, lead by Juan Carlos Izpisua Belmonte and Fred H. Gage, said the new cells transmit electrical impulses. That’s a sign that the cells were mature and functional – very neuronal-like.
Gage, who leads the Gene Expression Laboratory at Salk, is a long-time member of the Reeve Foundation Science Advisory Council; his lab was for many years a member of the Reeve International Research Consortium for Spinal Cord Injury.
The paper, “Cord blood-derived neuronal cells by ectopic expression of Sox2 and c-Myc
," appeared last week in the Proceedings of the National Academy of Sciences.
Headline writers, cued by the Salk PR office, framed it with great optimism: “Cord blood may help treat stroke, traumatic brain injury and spinal cord.” But the research isn’t quite ready for that clinical prediction.
From the published abstract:
Here we show that human cord blood (CB) CD133+ cells lose their hematopoietic signature and are converted into CB-induced neuronal-like cells (CB-iNCs) by the ectopic expression of the transcription factor Sox2, a process that is further augmented by the combination of Sox2 and c-Myc. Gene-expression analysis, immunophenotyping, and electrophysiological analysis show that CB-iNCs acquire a distinct neuronal phenotype characterized by the expression of multiple neuronal markers. CB-iNCs show the ability to fire action potentials after in vitro maturation as well as after in vivo transplantation into the mouse hippocampus. This system highlights the potential of CB cells and offers an alternative means to the study of cellular plasticity, possibly in the context of drug screening research and of future cell-replacement therapies.
While cord blood has a lot of promise, this study is cool because they were able to make a blood cell into to a nerve cell using a single transcription factor, Sox2, a protein switch that acts as a genetic switch. In previous studies, scientists reprogrammed skin cells to become very much like embryonic neural stem cells. These so called induced pluripotent stem cells required four transcription factors. “Unlike previous studies, where multiple transcription factors were necessary to convert skin cells into neurons, our method requires only one transcription factor to convert CB cells into functional neurons,” said Gage.
The researchers demonstrated that these CB cells, which come from the mesoderm, the middle layer of embryonic germ cells, can be switched to ectodermal cells, outer layer cells from which brain, spinal and nerve cells arise. “This study shows for the first time the direct conversion of a pure population of human cord blood cells into cells of neuronal lineage by the forced expression of a single transcription factor,” says Juan Carlos Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory, who led the research team.
The Salk researchers used a retrovirus to introduce Sox2. After testing the new cells, they determined that these induced neuronal-like cells (iNC), could transmit electrical impulses. They put the modified cord blood cells into a mouse brain; the cells integrated into the existing mouse neuronal network and were capable of transmitting electrical signals. There’s a lot of work to do to make the neo-neurons truly functional.
The next step is to refine the tricked-out cells toward a more specified state. More from Salk:
“We also show that the CB-derived neuronal cells can be expanded under certain conditions and still retain the ability to differentiate into more mature neurons both in the lab and in a mouse brain,” says Mo Li, a scientist in Belmonte’s lab and a co-first author on the paper with Alessandra Giorgetti, of the Center for Regenerative Medicine, in Barcelona, and Carol Marchetto of Gage’s lab. “Although the cells we developed were not for a specific lineage-for example, motor neurons or mid-brain neurons-we hope to generate clinically relevant neuronal subtypes in the future.”
Giorgetti notes a number of advantages the cord blood cells have over other types of stem cells. They are not embryonic stem cells and therefore not controversial. They are more plastic, or flexible, than adult stem cells from sources like bone marrow, which may make them easier to convert into specific cell lineages. Moreover, the collection of cord blood cells is safe and poses no risk to the donor. Cord blood can be stored in blood banks for later use. Presumably, one could search the banks for cord cells that are an immunological match to specific patients.