Stable, Self-Renewing Neural Stem Cells


Researchers at the University of California, San Diego School of Medicine, the Gladstone Institutes in San Francisco and colleagues reported a monumental advance in stem cell science: the creation of long-term, self-renewing, primitive neural precursor cells from human embryonic stem cells (hESCs) that can be directed to become many types of neuron without increased risk of tumor formation.

Kang Zhang, professor of ophthalmology and human genetics at Shiley Eye Center and director of the Institute for Genomic Medicine, at UC San Diego said, “It’s a big step forward . . . It means we can generate stable, renewable neural stem cells or downstream products quickly, in great quantities and in a clinical grade – millions in less than a week – that can be used for clinical trials and, eventually, for clinical treatments. Until now, that has not been possible.”

Human embryonic stem cells can become any kind of cell needed to repair and restore damaged tissues, and for this reason, a great deal of hope has been placed in them when it comes to regenerative medicine. But the potential of hESCs is constrained by practical problems, not least of which is the difficulty of growing sufficient quantities of stable, usable cells and the risk that some of these cells might form tumors.

To produce neural stem cells, Zhang, with co-author Sheng Ding, former professor of chemistry at The Scripps Research Institute and now at the Gladstone Institutes, and their colleagues added small molecules in a chemically defined culture condition that induces hESCs to become primitive neural precursor cells, but then halts further differentiation processes.

Zhang added, “And because it doesn’t use any gene transfer technologies or exogenous cell products, there’s minimal risk of introducing mutations or outside contamination.” Assays of these neural precursor cells found no evidence of tumor formation when introduced into laboratory mice.

By adding other chemicals, scientists were able to then direct the precursor cells to differentiate into different types of mature neurons. This means that you can explore potential clinical applications for a wide range of neurodegenerative diseases. You can generate neurons for specific conditions like amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease), Parkinson’s disease or eye-specific neurons that are lost in macular degeneration, retinitis pigmentosa or glaucoma.

The new process promises to have broad applications in stem cell research. The same method can be used to push induce pluripotent stem cells (stem cells artificially derived from adult, differentiated mature cells) to become neural stem cells. In principle, by altering the combination of small molecules, you might be able to create other types of stem cells capable of becoming heart, pancreas, or muscle cells. The next step is to use these stem cells to treat different types of neurodegenerative diseases, such as macular degeneration or glaucoma in animal models.

One problem this study does not address is the immunological rejection of implanted stem cells.  Deriving such cells from induced pluripotent stem cells would be a much more desirable and practical technology from a clinical standpoint.  Also, the use of induced pluripotent stem cells would not require the death of anymore young human beings.

Published by

mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).