26 Jul 2001

As the political debate about stem cell research heats up once again, scientists continue to wrestle with the most fundamental questions about these cells: Where do they come from? Are the stem cells scientists have extracted from the adult brain indeed direct descendants of the ones that built the organ during development? And how relevant can they truly be to the repair of the damaged brain?

A report in tomorrow's Science attempts to address these questions with a single experiment. Stem cell researcher Evan Snyder at Harvard Medical School collaborated with Curt Freed at the University of Colorado School of Medicine in Denver, best known for research on fetal transplantation in Parkinson's disease. The scientists injected a traceable clone of human neural stem cells (isolated originally from the ventricular zone of an aborted 15-week-old fetus) into a cerebral ventricle of fetal bonnet monkeys. A month later, they delivered the developing monkeys and looked to which brain areas the human neural stem cells had migrated.

The authors found human cells in two subpopulations. One set had traveled up to half an inch outward along radial glia. They had differentiated into neurons in cortical layers II/III, which were building up their neuronal populations during this developmental period, and into glial cells in the deeper layers IV-VI, which by this time had completed neurogenesis and progressed to adding glial cells in between the neurons. (The mammalian cortex develops in an inside-out fashion. Cells continuously generated deep inside the brain crawl outward past older ones to add new layers on the surface. Each cortical layer first becomes populated with neurons, and then adds glia.)

The second set of human cells remained undifferentiated and was dispersed mostly along the subventricular zone, which is widely considered to contribute to adult homeostasis. Yet small groups of human stem cells were also found intermixed with differentiated cells in the striatum and cortex. The authors suggest that their findings reflect an underlying strategy of neural stem cell allocation during development. The progeny of stem cells segregate to contribute to organogenesis on the one hand while setting aside some cells to establish resident pools of pluripotent cells throughout the brain on the other hand, the authors propose. Their findings also contradict the view that the stem cells recovered in earlier studies were artifacts of the experimental procedures or were dedifferentiated versions of previously mature cells.—Gabrielle Strobel