This microscope image shows a colony of neurons derived from cord-blood cells using stem cell reprogramming technology. The green and red glow indicates that the cells are producing protein makers found in neurons, evidence that the cord-blood cells did in fact morph into neurons. The blue glow marks the nuclei of the neurons. Image: Courtesy of Alessandra Giorgetti |
For
more than 20 years, doctors have been using cells from blood that
remains in the placenta and umbilical cord after childbirth to treat a
variety of illnesses, from cancer and immune disorders to blood and
metabolic diseases.
Now,
scientists at the Salk Institute for Biological Studies have found a
new way—using a single protein, known as a transcription factor—to
convert cord blood (CB) cells into neuron-like cells that may prove
valuable for the treatment of a wide range of neurological conditions,
including stroke, traumatic brain injury and spinal cord injury.
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 study, a collaboration with
Fred H. Gage, a professor in Salk’s Laboratory of Genetics, and his
team, was published on July 16 in the Proceedings of the National Academy of Sciences.
“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,” says
Gage.
The
Salk researchers used a retrovirus to introduce Sox2, a transcription
factor that acts as a switch in neuronal development, into CB cells.
After culturing them in the laboratory, they discovered colonies of
cells expressing neuronal markers. Using a variety of tests, they
determined that the new cells, called induced neuronal-like cells (iNC),
could transmit electrical impulses, signaling that the cells were
mature and functional neurons. Additionally, they transferred the
Sox2-infused CB cells to a mouse brain and found that they integrated
into the existing mouse neuronal network and were capable of
transmitting electrical signals like mature functional neurons.
“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.”
Importantly,
says Marchetto, “We could use these cells in the future for modeling
neurological diseases such as autism, schizophrenia, Parkinson’s or
Alzheimer’s disease.”
Cord
blood cells, says Giorgetti, offer a number of advantages over other
types of stem cells. First, they are not embryonic stem cells and thus
they are 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. The collection of CB
cells is safe and painless and poses no risk to the donor, and they can
be stored in blood banks for later use.
“If
our protocol is developed into a clinical application, it could aid in
future cell-replacement therapies,” says Li. “You could search all the
cord blood banks in the country to look for a suitable match.”
Other
researchers on the study were Diana Yu, Yangling Mu, Cedric Bardy and
Guang-Hui Liu, from the Salk Institute; and Rafaella Fazzina, Antonio
Adamo, Ida Paramonov, Julio Castaño Cardoso, Montserrat Barragan
Monasterio and Riccardo Cassiani-Ingoni of the Center for Regenerative
Medicine in Barcelona.
The
work was supported by the California Institute for Regenerative
Medicine, The Lookout Foundation, the G. Harold and Leila Y. Mathers
Charitable Foundation, the Leona M. and Harry B. Helmsley Charitable
Trust, the JPB Medical Foundation, MINECO, Fundacion Cellex and Sanofi.
Source: Salk Institute