sept30 2010
--The
ability to efficiently generate patient-specific stem cells
from differentiated cells and then reliably direct them to form
specialized cells (like neurons or muscle) has tremendous therapeutic
potential for replacing diseased or damaged tissues. However,
despite some successes, there have been significant limitations
associated with existing methods used to generate human induced
pluripotent stem cells (iPSCs).
Now,
a study published by Cell Press on September
30th in the journal Cell Stem Cell
presents a novel strategy for creating
iPSCs that exhibits some significant
advantages when compared with current
iPSC technologies. The new method does
not require risky genetic modification
and holds great promise for making the
reprogramming process more therapeutically
relevant.
"Clinical
application of iPSCs is currently hampered
by low efficiency of iPSC generation
and protocols that permanently alter
the genome to effect cellular reprogramming,"
explains senior study author, Dr. Derrick
J. Rossi from Harvard Medical School.
"Perhaps even more importantly, safe
and effective means of directing the
fate of patient-specific iPS cells towards
clinically useful cell types are lacking."
In
the current study, Dr. Rossi and colleagues
did not take the standard approach to
permanently alter the genome to achieve
expression of protein factors known
to reprogram adult cells into iPSCs.
Instead, they developed synthetic modified
messenger RNA molecules (which they
termed "modified RNAs") that encoded
the appropriate proteins but did not
integrate into the cell's DNA.
Repeated
administration of the modified RNAs
resulted in robust expression of the
reprogramming proteins in mature skin
cells that were then converted to iPSCs
with startling efficiency. "We weren't
really expecting the modified RNAs to
work so effectively, but the reprogramming
efficiencies we observed with our approach
were very high," says Dr. Rossi.
Importantly,
the modified RNA method was also used
to successfully to control the fate
of the iPSCs. "Creation of iPSCs is
the critical first step towards patient-specific
therapies, but to truly realize the
promise of iPS cell technology for regenerative
medicine or disease modeling, we must
harness the potential of iPS cells to
generate clinically useful cell types,"
notes Dr. Rossi. RNA-induced iPSCs with
an RNA associated with muscle cell development
caused the cells to differentiate into
muscle cells —again simply, efficiently
and without the immediate risk of inducing
genetic mutations.
These findings
demonstrate that the novel RNA-induced iPSC technology offers
significant advantages over existing methodologies. "Our technology
represents a safe, efficient strategy for somatic cell reprogramming
and directing cell fate that has wide ranging applicability
for basic research, disease modeling and regenerative medicine,"
concludes Dr. Rossi. "We believe that our approach has the potential
to become a major and perhaps even central enabling technology
for cell-based therapies."
Contact:
Cathleen Genova
cgenova@cell.com
617-397-2802
Article
via: from Eurekalert.com
