Illustrative Advances in Stem Cell Research

The field of stem cell research is very broad, very large, and very well funded nowadays - which we should all be appropriately thankful for, given its necessary part in producing the means to reverse the causes and consequences of aging. Regenerative medicine based on the transplant and manipulation of stem cells will be used for critical repairs in age-damaged tissues, and ultimately to replace or repair the stem cells and stem cell niches that have become too damaged to properly maintain the body. Progress towards stem cell therapies is much faster now than even ten years ago, and what would have been major advances back then, heralded in the popular press, are now routinely occurring on a weekly basis.

Stem cell research is also branching into many subfields and distinct, separate lines of research. There are efforts to make stem cell transplants more effective; work on finding signals that will override the programming of aged stem cells in the body; continuing efforts to find and classify populations of stem cells that are good sources for transplants or studies; initiatives seeking better ways to reprogram cells, such that ordinary cells can be transformed into stem cells, or stem cells guided to form specific cell types; and so on. Many distinct infrastructures are being built beneath the umbrella goal of regeneration from injury and aging, much of which involves finding ways to make cells to do as they are told, more effectively and at less expense.

Here are examples of recent advances in this sort of infrastructural work, efforts to make a branch of stem cell therapy or one of the underlying technologies more effective.

Antibody Transforms Stem Cells Directly Into Brain Cells

[Researchers screened] for antibodies that could activate the GCSF receptor, a growth-factor receptor found on bone marrow cells and other cell types. GCSF-mimicking drugs were among the first biotech bestsellers because of their ability to stimulate white blood cell growth - which counteracts the marrow-suppressing side effect of cancer chemotherapy. 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. The cells were reminiscent of neural progenitor cells -- which further tests for neural cell markers confirmed they were.

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."

Stem Cell Transplant Restores Memory, Learning in Mice

Human embryonic stem cells have been transformed into nerve cells that helped mice regain the ability to learn and remember. Once inside the mouse brain, the implanted stem cells formed two common, vital types of neurons, which communicate with the chemicals GABA or acetylcholine.

[Researchers] chemically directed the human embryonic stem cells to begin differentiation into neural cells, and then injected those intermediate cells. Ushering the cells through partial specialization prevented the formation of unwanted cell types in the mice. Ensuring that nearly all of the transplanted cells became neural cells was critical. "That means you are able to predict what the progeny will be, and for any future use in therapy, you reduce the chance of injecting stem cells that could form tumors. In many other transplant experiments, injecting early progenitor cells resulted in masses of cells - tumors. This didn't happen in our case because the transplanted cells are pure and committed to a particular fate so that they do not generate anything else. We need to be sure we do not inject the seeds of cancer."

The mice were a special strain that do not reject transplants from other species. After the transplant, the mice scored significantly better on common tests of learning and memory in mice. For example, they were more adept in the water maze test, which challenged them to remember the location of a hidden platform in a pool.


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