The corticospinal tract extends from the cerebral cortex in the upper brain down into the spinal cord tissue and is integral for controlling voluntary movement.
Regenerating this tissue would improve mobility in people who have suffered spinal cord damage, but so far such efforts have been unsuccessful, according to the senior author of a study published yesterday in the journal Nature Medicine.
“Previous attempts failed because an appropriate substance or cell type for the corticospinal tracts to grow through had not been identified,” Mark Tuszynski, professor in the UC San Diego (UCSD) School of Medicine Department of Neurosciences, told Biopharma-Reporter.com.
His team demonstrated successful regeneration of the corticospinal tract in rats by grafting multipotent neural stem cells into sites of corticospinal injury in rats and directing the cells to specifically develop as a spinal cord.
“A combination of growth factors, chemicals and cell culture dish coatings – ‘substrates’ - are used to programme these cells to become spinal cord cells,” he said.
Neural stem cells were tested for the first time and have shown they can support regeneration, he added.
“We tested cells from a variety of sources, including ‘approved’ embryonic stem cell lines, as well as mouse and rat stem cells. We also reprogrammed cells from adult human skin to become neural cells, and drove these to spinal cord cells. This approach works with a variety of cell types, as long as they are driven to a spinal cord fate.”
The research is still in its early stages, but may be a major breakthrough in treating spinal injuries, Tuszynski continued.
“This identifies, in our opinion, the optimal cell type to use in a potential treatment for spinal cord injury.”
Stem Cells in a Bottle
The research was carried out at the UCSD School of Medicine and Veterans Affairs San Diego Healthcare System, along with scientists in Japan and Wisconsin, but Tuszynski said there has so far been no involvement from Biopharma.
Industry interest in using stem cells in regenerative medicine is increasing.
For example, California-based biopharma firm StemCells has a candidate in Phase II clinical trials targeting regeneration in the cervical region of the spine using its using its HuCNS-SC, human neural stem cell platform.
The company first isolated and expanded human neural stem cells in 1999. Monoclonal antibodies are used against specific cell surface markers to prospectively isolate the population of neural stem cells from human brain tissue, which are then purified and expanded into cryopreserved cell banks.
According to StemCells, “a single ‘bank’ of stem cells derived from an original tissue source can supply a multitude of human doses, depending on the dose used in the indication.”
Furthermore, the firm claims “HuCNS-SC cells can ultimately be manufactured at commercial-scale as ‘stem cells in a bottle,’ then distributed for patient doses, much like an off-the-shelf pharmaceutical product for on-demand use.”
Source: NATURE MEDICINE
Title: ‘Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration’
Authors: Ken Kadoya, Paul Lu, Kenny Nguyen, Corinne Lee-Kubli, Hiromi Kumamaru, Lin Yao, Joshua Knackert, Gunnar Poplawski, Jennifer N Dulin, Hans Strobl, Yoshio Takashima, Jeremy Biane, James Conner, Su-Chun Zhang & Mark H Tuszynski