The team soon isolated one antibody type or "clone" that could activate the GCSF receptor and stimulate growth in test cells. The researchers then tested an unanchored, soluble version of this antibody on cultures of bone marrow stem cells from human volunteers. Whereas the GCSF protein, as expected, stimulated such stem cells to proliferate and start maturing towards adult white blood cells, the GCSF-mimicking antibody had a markedly different effect.
"The cells proliferated, but also started becoming long and thin and attaching to the bottom of the dish," remembered Xie.
To Lerner, the cells were reminiscent of neural progenitor cells—which further tests for neural cell markers confirmed they were.
A New Direction
Changing cells of marrow lineage into cells of neural lineage—a direct identity switch termed "transdifferentiation"—just by activating a single receptor is a noteworthy achievement. Scientists do have methods for turning marrow stem cells into other adult cell types, but these methods typically require a radical and risky deprogramming of marrow cells to an embryonic-like stem-cell state, followed by a complex series of molecular nudges toward a given adult cell fate. Relatively few laboratories have reported direct transdifferentiation techniques.
"As far as I know, no one has ever achieved transdifferentiation by using a single protein—a protein that potentially could be used as a therapeutic," said Lerner.
Current cell-therapy methods typically assume that a patient's cells will be harvested, then reprogrammed and multiplied in a lab dish before being re-introduced into the patient. In principle, according to Lerner, an antibody such as the one they have discovered could be injected directly into the bloodstream of a sick patient. From the bloodstream it would find its way to the marrow, and, for example, c
|SOURCE Scripps Research Institute|
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