It was first discovered that antibodies can directly transform bone marrow stem cells into neural progenitor cells

In an unexpected discovery, researchers at the Scripps Research Institute discovered a method to directly convert bone marrow stem cells into brain cells. Prior to this, the technique of transforming a patient's bone marrow stem cells into some other type of cell was relatively cumbersome and risky, and had only limited applicability. This new discovery may provide a simpler and more effective technology. Cell therapy using the patient's own cells is expected to be used to treat spinal cord injury, stroke, and other systemic diseases, and rarely poses a risk of immune rejection. Related research results were published online in the PNAS journal on April 22, 2013.

In this study, the researchers sought antibodies developed in the laboratory to activate growth-stimulating receptors on the surface of bone marrow stem cells. As a result, they discovered that an antibody activates this receptor to induce bone marrow stem cells (normal Under conditions, only white blood cells are produced) into neural progenitor cells, where neural progenitor cells are a class of almost mature brain cells.

In 2012, the researchers developed a new antibody discovery technology: mammalian cells are incubated with receptors or other molecules of interest to produce antibodies, allowing them to quickly determine which antibodies in the antibody library bind to a given receptor At the same time, it also allows them to quickly determine which antibodies activate this receptor and thereby change the function of the cell.

In this new study, Richard A. Lerner, a professor in the Cell and Molecular Biology Department at the Scripps Research Institute, and Jia Xie, an assistant researcher in the Lerner laboratory, and colleagues have improved this technology to enable antibodies produced by a given cell Anchored to the outer membrane of the cell in order to access its target receptor. Xie said, "Limiting the activity of antibodies to the cells that efficiently produce it allows us to use a larger antibody library to screen antibodies with specific activities more quickly." Using this improved technology, they were able to Screen a library of tens of millions of antibody molecules within a few days.

In early tests, Xie used this new method to screen for antibodies that can activate granulocyte colony stimulating factor (GCSF) receptors, which are found in bone marrow stem cells and other types of cells .

The researchers quickly isolated an antibody type that activates this GCSF receptor and promotes the growth of the test cells. They then tested the soluble protein version of this antibody, which was not anchored on the outer membrane of the cells, in bone marrow stem cell cultures from volunteers. Although as expected, this GCSF receptor promotes the proliferation of this stem cell and begins to differentiate into mature white blood cells, but this antibody that mimics GCSF exerts a significantly different effect: this stem cell proliferation also begins to become thin It is long and also attached to the bottom of the dish. The elongated cells formed were similar to neural progenitor cells, and further testing of neural cell markers confirmed that they were indeed neural progenitor cells.

Simply turning a single bone marrow stem cell line into a neural progenitor cell line by activating a single receptor is a remarkable achievement. This process of directly changing the identity of the cell is also called transdifferentiation. Scientists do have methods to transform bone marrow stem cells into other types of mature cells, but these methods usually require reprogramming bone marrow stem cells to a state similar to embryonic stem cells (which is extremely exciting and risky), and then under the action of a series of molecules , They transform into a mature cell with a characteristic. However, only relatively few laboratories have reported direct transdifferentiation techniques.

Although the researchers are still not sure why this new antibody has such a strange effect on this GCSF receptor, they speculate that it will bind to this receptor longer than natural GCSF, and this longer mutual The effect changes the signal transduction mode of this receptor.

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