Antibody Transforms Stem Cells Directly into Brain Cells

Mika Ono 858-784-2052 mikaono@scripps.edu

Newswise LA JOLLA, CA April 22, 2013 In a serendipitous discovery, scientists at The Scripps Research Institute (TSRI) have found a way to turn bone marrow stem cells directly into brain cells.

Current techniques for turning patients marrow cells into cells of some other desired type are relatively cumbersome, risky and effectively confined to the lab dish. The new finding points to the possibility of simpler and safer techniques. Cell therapies derived from patients own cells are widely expected to be useful in treating spinal cord injuries, strokes and other conditions throughout the body, with little or no risk of immune rejection.

These results highlight the potential of antibodies as versatile manipulators of cellular functions, said Richard A. Lerner, the Lita Annenberg Hazen Professor of Immunochemistry and institute professor in the Department of Cell and Molecular Biology at TSRI, and principal investigator for the new study. This is a far cry from the way antibodies used to be thought ofas molecules that were selected simply for binding and not function.

The researchers discovered the method, reported in the online Early Edition of the Proceedings of the National Academy of Sciences the week of April 22, 2013, while looking for lab-grown antibodies that can activate a growth-stimulating receptor on marrow cells. One antibody turned out to activate the receptor in a way that induces marrow stem cellswhich normally develop into white blood cellsto become neural progenitor cells, a type of almost-mature brain cell.

Natures Toolkit

Natural antibodies are large, Y-shaped proteins produced by immune cells. Collectively, they are diverse enough to recognize about 100 billion distinct shapes on viruses, bacteria and other targets. Since the 1980s, molecular biologists have known how to produce antibodies in cell cultures in the laboratory. That has allowed them to start using this vast, target-gripping toolkit to make scientific probes, as well as diagnostics and therapies for cancer, arthritis, transplant rejection, viral infections and other diseases.

In the late 1980s, Lerner and his TSRI colleagues helped invent the first techniques for generating large libraries of distinct antibodies and swiftly determining which of these could bind to a desired target. The anti-inflammatory antibody Humira, now one of the worlds top-selling drugs, was discovered with the benefit of this technology.

Last year, in a study spearheaded by TSRI Research Associate Hongkai Zhang, Lerners laboratory devised a new antibody-discovery techniquein which antibodies are produced in mammalian cells along with receptors or other target molecules of interest. The technique enables researchers to determine rapidly not just which antibodies in a library bind to a given receptor, for example, but also which ones activate the receptor and thereby alter cell function.

Lab Dish in a Cell

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Antibody Transforms Stem Cells Directly into Brain Cells