Nov 05, 2002
By Karla Gale
By implanting a biodegradable scaffold along with neural stem cells into large brain lesions, the donor and host cells' regenerative ability is vastly improved in a murine model of severe cerebral palsy, according to a Nature Biotechnology study published online October 15th.
"We also showed that there is real cross-talk in a stem cell implant," coauthor Dr. Evan Y. Snyder, of Harvard Medical School in Boston, told Reuters Health. "People often think of stem cells as initiating a one-way conversation. What we saw here is that the brain 'talks' to the stem cell and the stem cell 'talks' to the brain during the repair process."
In their study, Dr. Snyder's team seeded cultured lacZ-expressing murine neural stem cells onto a woven array of polyglycolic acid (PGA) fibers. They then implanted these "biobridges" into the evolving infarction cavity induced 7 days earlier in week-old mice by ligation of the right common carotid artery followed by hypoxia.
The implants forestalled the parenchymal loss normally seen in this type of injury and became incorporated into the injured cerebrum, the authors maintain, with vascularization apparent 2 weeks later. This suggests "not only assimilation of donor with host tissues but an intimate communication between the two, possibly including elaboration of angiogenic signals," they write.
In contrast to animals implanted with PGA alone, stem cells alone, or placebo, the mice with stem cells and PGA scaffolds exhibited normal behavior.
The lacZ-expressing donor cells differentiated into neurons and oligodendrocytes, even extending axons into the contralateral hemisphere. A web of neuronal fibers interconnected with residual PGA contained neurons derived from both the host and donor, the report indicates. In addition, neurons in the intact hemisphere were found to extend their axons toward the reconstituted cortical penumbra.
"The intricate reciprocal interactions between the neural stem cell-PGA complex and injured brain appeared additionally to promote arborization of host neurites," the researchers note. While all this was happening, they found that mononuclear cell infiltration and astroglial scarring were greatly diminished in the treatment group compared with the control group.
"Theoretically, this approach should be useful not only for brain disease where a vast amount of tissue is lost, but maybe even for other organs, such as the heart, pancreas, or gut," Dr. Snyder said.
He and his colleagues hope next to identify the molecules that allowed for the donor-host "cross-talk," Dr. Snyder said. They also want to replicate these results using human neural stem cells, both in vitro and in vivo by implantation into immunosuppressed mice.
"If that works, then we will scale up to a large animal model, such as a monkey or goat," Dr. Snyder added.
© 2002 Reuters Ltd