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Salk Institute scientists have isolated cells from the brains of human cadavers that can grow, divide and form specialized classes of brain cells.
Their findings indicate that postmortem tissue may be a potential source of multipotent stem cells with a variety of uses and applications.
"I find it remarkable that we all have pockets of cells in our brains that can grow and differentiate throughout our lives and even after death," said Fred Gage, a professor at The Salk Institute and senior author of the study, which appears in the current Nature.
Previous attempts to recover progenitor cells from adult tissue had failed, but the Gage laboratory applied growth factors to extracted tissue that appear to have made a crucial difference. These factors include FGF-2 (fibroblast growth factor 2) and cystatin C, which were added to the culture medium that bathed the cells.
"Clearly, establishing the right conditions is critical to encouraging growth and differentiation," said Gage. "We isolated cystatin C recently, and although we're still working to optimize conditions, it's made a major difference in our ability to cultivate these cells."
The investigators obtained postmortem or biopsy tissue from 23 individuals, ranging in age from 11 weeks to 72 years old. Tissue from older individuals yielded fewer proliferating cells.
Importantly, the recovered cells had the ability to differentiate into different types of brain cells. The cell types observed include neurons, the cells that form the "wiring" of the nervous system; astrocytes, which nourish and protect neurons; and oligodendrocytes, which insulate neurons with a myelin sheath.
"This study employed a pool of cells from extracted tissue," said Gage. "We haven't yet isolated individual cells from that pool and followed them to see if a single cell can give rise to multiple classes of brain cells," said Gage. "Such a cell would be a neural stem cell by a strict definition."
The study employed postmortem and biopsy tissue from individuals with a number of neurological disorders including epilepsy and myofibromatosis. The cells derived from these tissues constitute a model system for studying the brain cell biology of these disorders, according to Gage.
"Cells recovered from healthy individuals could provide a model for understanding how to stimulate and guide the normal processes of brain cell growth and differentiation," he said, "lending insight to how growth might be stimulated in people suffering from neurodegenerative diseases such as Alzheimer's or Parkinson's."
In addition to isolating single cells in order to determine if true stem cells are present in adult brain tissue, Gage also plans to transplant recovered cells into animals to test if the cells can survive and differentiate in vivo.
"Testing in whole animals is the only way to know if adult tissue can be a source of stem or progenitor cells for transplant purposes to treat neurodegenerative disease," said Gage.
An adult source of stem cells would circumvent the need to derive such cells from fetal tissue, currently an issue of ethical debate.
First author of the study is Theo Palmer, former research associate in the Gage laboratory and currently an assistant professor at Stanford University. Additional Salk co-authors include Phillipe Taupin and Brian Kaspar. The study was done in collaboration with Phillip Schwartz and Stuart Stein at Children's Hospital of Orange County, Calif. The study, titled "Progenitor cells grown from postmortem human brain," was supported by the National Institutes of Health, the National Institute of Aging, the Lookout Fund and the Christopher Reeves Paralysis Foundation.
The Salk Institute for Biological Studies, located in La Jolla, Calif., is an independent nonprofit institution dedicated to fundamental discoveries in the life sciences, the improvement of human health and conditions, and the training of future generations of researchers.
The Institute was founded in 1960 by Jonas Salk, M.D., with a gift of land from the City of San Diego and the financial support of the March of Dimes Birth Defects Foundation. - By Suzanne Clancy
Image of proliferating brain cells (http://www.salk.edu/NEWS/gage043001/gage043001img.html)
The Salk Institute for Biological Studies (http://www.salk.edu/)
Clancy, Warren Froelich ]