New method for generating human stem cells is remarkably efficient

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New method for generating human stem cells is remarkably efficient

http://www.eurekalert.org/pub_releases/2010-09/cp-nmf092410.php

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. "