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Biological Chemistry

Stem Cell Multiplier

Medicinal Chemistry: Small molecule spurs the proliferation of blood stem cells

by Sarah Everts
August 9, 2010 | APPEARED IN VOLUME 88, ISSUE 32

Propagation Aid
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Credit: Science
As shown in these optical microscopy images, SR1 helps blood stem cells proliferate (various colors, right) instead of differentiating into blood cells (purple, left) after five days. Images are at 40× magnification
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Credit: Science
As shown in these optical microscopy images, SR1 helps blood stem cells proliferate (various colors, right) instead of differentiating into blood cells (purple, left) after five days. Images are at 40× magnification

Researchers in California are reporting a small molecule that might help human blood stem cells propagate. The molecule, called SR1, also targets a receptor not previously known to play a role in blood stem cell biology.

The intention of the new work is to increase the supply of these valuable human blood stem cells, which are required to replenish the blood and immune systems of leukemia patients and those experiencing the aftereffects of radiation therapy.

Blood stem cells, also known as hematopoietic stem cells, have been transplanted directly from bone marrow or umbilical cord blood donors into patients for decades. However, researchers have long wanted to find a way to cultivate the valuable cells in a lab prior to transplantation so that more patients could be treated from one donation. For instance, the stem cells in one umbilical cord blood donation aren’t enough to treat an adult, so the treatment is limited to children unless multiple suitable donors are found.

Researchers led by Peter G. Schultz at Scripps Research Institute and Michael P. Cooke at the Genomics Institute of the Novartis Research Foundation (GNF) screened a library of 100,000 heterocycles to find SR1, 
a purine derivative that, when added to a protein cocktail, multiplies the number of blood stem cells 17 times 
(Science, DOI: 10.1126/science.1191536).

“It’s an important advance,” comments Harvey F. Lodish, a stem cell researcher at Whitehead Institute for Biomedical Research. SR1 replaces two protein components in a cocktail previously developed by Lodish and his former postdoc Chengcheng Zhang, now a stem cell biologist at the University of Texas Southwestern Medical Center. That cocktail, which propagates blood stem cells by an amount similar to the SR1-containing mixture, will soon go into clinical trials at Singapore General Hospital.

Using the small molecule instead of proteins could simplify procedures to propagate blood stem cells should they reach a clinical setting, comments Christopher Y. Park, who specializes in stem cells and cancer at Memorial Sloan-Kettering Cancer Center.

The Scripps and GNF researchers report that SR1 works by antagonizing the aryl hydrocarbon receptor, a previously unknown player in blood stem cell biology. “This opens up the possibility of further understanding how human hematopoietic stem cells are regulated, which then allows one to try to modulate human hematopoietic stem cell activity for clinical benefit in other ways,” comments Hal E. Broxmeyer, a stem cell researcher at Indiana University School of Medicine.

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