SIMPLE METHOD TURNS HUMAN SKIN CELLS IN TO IMMUNE STRENGTHENING WHITE BLOOD CELLS
For the first time,
scientists have turned human skin cells into transplantable white blood cells,
soldiers of the immune system that fight infections and invaders. The work,
done at the Salk Institute, could let researchers create therapies that
introduce into the body new white blood cells capable of attacking diseased or
cancerous cells or augmenting immune responses against other disorders
The work, as detailed
in the journal Stem Cells, shows that only a bit of creative
manipulation is needed to turn skin cells into human white blood cells.
"The process is quick
and safe in mice," says senior author Juan Carlos Izpisua Belmonte, holder
of Salk's Roger Guillemin Chair. "It circumvents long-standing obstacles
that have plagued the reprogramming of human cells for therapeutic and
regenerative purposes."
Those problems
includes the long time -- at least two months -- and tedious laboratory work it
takes to produce, characterize and differentiate induced pluripotent stem (iPS)
cells, a method commonly used to grow new types of cells. Blood cells derived
from iPS cells also have other obstacles: an inability to engraft into organs
or bone marrow and a likelihood of developing tumors.
The new method takes
just two weeks, does not produce tumors, and engrafts well.
"We tell skin
cells to forget what they are and become what we tell them to be -- in this
case, white blood cells," says one of the first authors and Salk
researcher Ignacio Sancho-Martinez. "Only two biological molecules are
needed to induce such cellular memory loss and to direct a new cell fate."
Belmonte's team
developed the faster technique (called indirect lineage conversion) and
previously demonstrated that these approaches could be used to produce human
vascular cells, the ones that line blood vessels. Rather than reversing cells
all the way back to a stem cell state before prompting them to turn into
something else, such as in the case of iPS cells, the researchers
"rewind" skin cells just enough to instruct them to form the more
than 200 cell types that constitute the human body.
The technique
demonstrated in this study uses a molecule called SOX2 to become somewhat
plastic -- the stage of losing their "memory" of being a specific
cell type. Then, researchers use a genetic factor called miRNA125b that tells
the cells that they are actually white blood cells.
The researchers are
now conducting toxicology studies and cell transplantation proof-of-concept
studies in advance of potential preclinical and clinical studies.
"It is fair to
say that the promise of stem cell transplantation is now closer to
realization," Sancho-Martinez says.
Study co-authors
include investigators from the Center of Regenerative Medicine in Barcelona,
Spain, and the Centro de Investigacion Biomedica en Red de Enfermedades Raras
in Madrid, Spain.
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