Researchers from UT Southwestern Medical Center announce in a recent study their success at boosting the regeneration of mature nerve cells in the spinal cords of adult mammals.
Senior author Dr Chun-Li Zhang, associate professor of Molecular Biology at UT Southwestern, and his team focus on glial cells, which support nerve cells in the spinal cord and form scar tissue in response to injury.
In their study, Zhang and his team created new nerve cells in the brains and spinal cords of mice by introducing transcription factors that promoted the transition of adult glial cells into more primitive, stem cell-like states, and then coaxed them to mature into adult nerve cells. The number of new spinal nerve cells generated by this process was low, however, leading researchers to focus on ways to amplify adult neuron production, , explains a media release from UT Southwestern Medical Center
In a two-step process, the researchers first silenced parts of the p53-p21 protein pathway that acts as a roadblock to the reprogramming of glial cells into the more primitive, stem-like types of cells with potential to become nerve cells. Although the blockade was successfully lifted, many cells failed to advance past the stem cell-like stage. In the second step, they screened mice for factors that could boost the number of stem-like cells that matured into adult neurons.
Via this process, the scientists identified two growth factors — BDNF and Noggin — that accomplished this goal. The team then was able to increase the number of newly matured neurons by tenfold, the release continues.
“Silencing the p53-p21 pathway gave rise to progenitor (stem-like) cells, but only a few matured. When the two growth factors were added, the progenitors matured by the tens of thousands,” Zhang says in the release.
Further experiments that looked for biomarkers commonly found in nerve cell communication indicated that the new neurons may form networks, he adds.
“Because p53 activation is thought to safeguard cells from undergoing uncontrolled proliferation, as in cancer, we followed mice that had temporary inactivation of the p53 pathway for 15 months without observing any increased cancer risk in the spinal cord,” he states.
“Our ability to successfully produce a large population of long-lived and diverse subtypes of new neurons in the adult spinal cord provides a cellular basis for regeneration-based therapy for spinal cord injuries. If borne out by future studies, this strategy would pave the way for using a patient’s own glial cells, thereby avoiding transplants and the need for immunosuppressive therapy,” he concludes, per the release.
The study was published recently in Cell Reports.
[Source(s): UT Southwestern Medical Center, Science Daily]