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Researchers grow human astrocytes in situ for the first time for potential ALS cure.

Researchers from the University of Wisconsin have developed a unique model for learning more about the role of human astrocytes.  The findings may lay a foundation for the treatment of a number of neurodegenerative diseases, including ALS (amyotrophic lateral sclerosis) and debilitating spinal cord injuries.  The team state that they expect astrocytes may help neuronal survival and improve disease conditions in ALS and spinal cord injury.  Studies are now ongoing because of these findings.  The current opensource study is published in the Journal of Clinical Investigation.

Astrocytes, so named because of their star shape, are thought to perform a number of important roles in the human brain and spinal cord, and in human health and disease. Animal studies show they are necessary for the development and maintenance of healthy neurons, proper nervous system signaling, and in the formation and maintenance of the crucial blood-brain barrier.  Defects in astrocytic function are associated with ALS and diseases like Rett syndrome, Alexander disease and Huntington’s disease.

The medical community knows very little about human astrocytes, with it commonly being held that they are crucial in human health and disease.  However, studying astrocytes is very difficult.  This is especially true of studying human astrocytes in adults. Previous studies have used newborn mice, which provide a different biological environment for astrocytes, yet at least some of these neurodegenerative diseases, and many spinal cord injuries, occur in human adults.

To overcome this problem the team transplanted immature human nervous system cells, generated from adult stem cells, into the spinal cords of mice. These cells matured into astrocytes.  The researchers checked in from time to time, and within nine months, found the astrocytes had travelled long distances along the mouse spinal cord, hugging the mouse neurons, connecting to blood vessels and joining with one another, just as mouse astrocytes do. They replaced the mouse astrocytes in the process, but did not affect the ability of the mice to function normally.

The team were amazed at this positive outcome.  The researchers suspect that what may actually be happening is the human astrocytes are out-dividing their smaller, mouse counterparts, developing in larger numbers and essentially ‘pushing’ the mouse cells out via natural selection.

The researchers repeated the experiments with astrocytes matured from human patients with ALS. The astrocytes replaced the mouse astrocytes, behaving just like those from nonALS individuals, except they disrupted motor function in the mice, just like in ALS.  The team observed that these mice had problems with movement in their legs and were just beginning to show signs of neuron degeneration.  This showed the researchers that it’s not just a physical replacement, it’s really a functional integration with consequence.

The team now plan to take these findings in the lab to human patients in the clinic.  The team feel that stem cells can be utilized for medical purposes and plan to treat spinal cord injury, and especially ALS.

Source:  Board of Regents of the University of Wisconsin System

Integration of astrocytes from patients with ALS and its effect on mouse MNs.  Integration of astrocytes from patients with ALS and its effect on mouse MNs. Human-derived neural progenitors functionally replace astrocytes in adult mice.  Zhang et al 2015.
Integration of astrocytes from patients with ALS and its effect on mouse MNs. Integration of astrocytes from patients with ALS and its effect on mouse MNs. Human-derived neural progenitors functionally replace astrocytes in adult mice. Zhang et al 2015.

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