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Reprogramming patients' cells offers powerful new tool for studying, treating blood diseases
Date:7/30/2013

esearchers corrected the genetic defect that causes DBA, the iPSCs developed into red blood cells in normal quantities. "This showed that in principle, it's possible to repair a patient's defective cells," said Weiss.

Weiss cautioned that this proof-of-principle finding is an early step, with many further studies to be done to verify if this approach will be safe and effective in clinical use.

However, he added, the patient-derived iPSCs are highly useful as a model cell system for investigating blood disorders. For instance, DBA is often puzzling, because two family members may have the same mutation, but only one may be affected by the disease. Because each set of iPSCs is specific to the individual from whom they are derived, researchers can compare the sets to identify molecular differences, such as a modifier gene active in one person but not the other.

Furthermore, the cells offer a renewable, long-lasting model system for testing drug candidates or gene modifications that may offer new treatments, personalized to individual patients.

The second study in Blood provides a concrete example of using iPSCs for drug testing, specifically for the often-aggressive childhood leukemia, JMML. First the study team generated iPSCs from two children with JMML, and then manipulated the iPSCs in cell cultures to produce myeloid cells that multiplied uncontrollably, much as the original JMML cells do.

They then tested the cells with two drugs, each able to inhibit a separate protein known to be highly active in JMML. One drug, an inhibitor of the MEK kinase, reduced the proliferation of cancerous cells in culture. "This provides a rationale for a potential targeted therapy for this specific subtype of JMML," said Weiss.

A stem cell core facility at CHOP, directed by study co-author Deborah French under the auspices of the hospital's Center for Cellular and Molecular Therapeutics, generated the iPSCs lines used in these
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Contact: John Ascenzi
Ascenzi@email.chop.edu
267-426-6055
Children's Hospital of Philadelphia
Source:Eurekalert

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