Stem cells isolated from human embryos were injected into rats suffering from neuronal damage caused by a virus. The stem cells helped recover movement by releasing growth factors that helped the damaged neurons to recover.
In their experiments, spearheaded and majorly funded by the private organization Project ALS, the scientists first infected rats with a virus (Sindbis) they developed that selectively destroys nerve cells that control muscles in the hind limbs. Lou Gehrig's disease, also known as ALS or amyotrophic lateral sclerosis, is similarly marked by a gradual loss of the nerves that control muscles, although its cause is unknown.
One-third of the animals then received transplants of human embryonic germ cells, which are capable of becoming any cell type, into their spinal fluid. The other rats served as controls and received either hamster kidney cells or human cells that don't have stem cell properties.
Twelve weeks later, the 15 paralyzed rats that got human stem cells partially recovered control of their hind limbs. Moreover, their hind limbs were 40 percent stronger than control animals'. By 24 weeks, 11 of the 15 turned over at least three seconds faster when placed on their backs than before getting the human cells. Control rats did not improve, on average, over the 24 weeks of the study.
In paralyzed rats, Kerr and his team found that most of the implanted human cells migrated into the spinal cord, and many became cells of the nervous system -- astrocytes, neurons and even motor neurons -- while in uninjured animals the transplanted cells just sat on the spinal cord's outer surface. However, even in injured animals, only about four human cells per rat became motor neurons that actually extended out of the spinal cord and into muscle, potentially creating a circuit that could control movement.
"We saw some physical recovery, and we saw human stem cells that had become motor neurons, but it turns out that the two observations weren't related," says Kerr. "We saw functional recovery that wasn't due to new neurons, and we had no idea how that could be possible."
Kerr then discovered that the rats' own neurons were healthier in animals that received human stem cells. In subsequent laboratory experiments, Kerr found that the human stem cells produced copious amounts of two key growth signals. These were transforming growth factor-alpha (TGF-alpha), which promotes neurons' survival, and brain derived neurotrophic factor (BDNF), which strengthens their connections to other neurons. When the scientists blocked these two signals in the laboratory, the stem cells' beneficial effects disappeared.
"Even before motor neurons die, connecting neurons peel back as if they sense a sinking ship," says Kerr. "Simply keeping a neuron alive can't improve physical abilities if it's not connected to other neurons. It must be part of a circuit.
"In some ways our results reduce stem cells to the non-glamorous role of protein factories, but the cells still do some amazing, glamorous things we can't explain," he adds. "For example, the white matter that surrounds the spinal cord was thought to be an impenetrable barrier to axon growth, but some of the transplanted cells not only migrated into the spinal cord, but also sent axons back out. It is just incredible."
This is the second study to come out in the last couple of weeks that showed a beneficial effect from stem cells where the stem cells worked their benefit by releasing compounds that transformed other existing cells. The other was the use of bone marrow stem cells to restore insulin production to existing pancreatic cells. These are surprising results.
These two sets of results suggest that in addition to serving as a supply of new cells to replace damaged or lost cells a normal function of stem cells may be to supply signals to encourage growth and change of cell type in existing non-stem cells.
These results also make me think that the therapeutic value of stem cells as growth factor delivery vehicles could be enhanced by genetic engineering. If stem cells are needed to deliver a particular growth factor or set of growth factors then their effects might be able to be enhanced by genetically engineering them to produce more of whichever growth factors are needed for a specific therapeutic purpose. Damaged neurons need different growth factors than damaged pancreatic cells for instance. So it makes sense to use gene therapy to program stem cells to produce the exact growth factors needed for each purpose.
|Share |||Randall Parker, 2003 June 29 09:18 PM Biotech Therapies|