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Researchers near goal of using a patient's own cells to make stem cells


Defective BRCA1 causes aberrant expression of non-coding satellite RNA that leads to genomic instability, thereby promoting cancer development. The image shows that overproduction of satellite RNA leads to an abnormal number of centrosomes in a normal human epithelial cell. Centrosomes are pictured in red, tublin in green and chromosomes in blue. The "mirrored" image in the Sputnik satellite is a confocal microscopic image. Center: a mathematical reconstruction of the confocal image to resolve the tubulin fibers and the individual chromosomes.
Image: Quan Zhu (confocal image); Jamie Simon (composition), Salk Institute for Biological Sciences; James Fitzpatrick (reconstructed image) Waitt Advanced Biophotonics Center.

A team in the lab of Inder Verma has developed an improved technique for generating large numbers of blood cells from a patient's own cells. The new technique, published in the journal Stem Cells, will be immediately useful in further stem cell studies and when perfected, could be used in stem cell therapies for a wide variety of conditions, including cancers and immune ailments.

Stem cell researchers have been racing toward this goal since 2006, when techniques for turning ordinary skin cells into induced pluripotent stem cells (iPSCs) were first reported. In principle, iPSCs mimic the embryonic stem cells (ESCs) from which organisms develop. However, researchers don't know yet how to induce iPSCs to become tissue-specific stem cells or mature tissue cells with high efficiency.

Like many other laboratories, the Verma lab has been seeking more efficient ways to turn iPSCs into blood-forming hematopoietic stem cells (HSCs). These may be more valuable medically than any other tissue-specific stem cell because they can supply not only oxygencarrying red blood cells but also all the white blood cells of the immune system.

In this study, the research team took seven lines of human ESCs and iPSCs and experimented with different combinations and sequences of growth factors and other chemical compounds that are known to be present as ESCs move to the HSC state in a developing human. Applying cocktails of these factors, the researchers induced the iPSCs and ESCs to form colonies of cells that bore the distinctive molecular markers of blood cells. With their best such cocktail, they were able to detect blood-specific markers on 84% of their cells after three weeks—a big jump in efficiency from just a few years ago.

Although the technique still has room for improvement—the researchers detected progenitor cells and mature cells from only one category or lineage, and the blood cell population they produced from ESCs and iPSCs contained no indefinitely renewing, transplantable HSCs— Verma notes, "We're now tantalizingly close to our ultimate goal."