Cell transplantation cite to treat spinal cord injury
Transplanting neural stem/progenitor cells (NS/PCs) into the spinal cord promotes functional recovery after spinal cord injury (SCI). However, which transplantation sites provide the best benefit?
This question was investigated by a Japanese research team and their findings will be published in a future issue of Cell Transplantation, but are currently freely available on-line as an unedited early e-pub.
"It is critical to determine the optimal transplantation site for NS/PCs aimed at treating SCI," said Dr. Masaya Nakamura of the Department of Orthopedic Surgery at the Keio University School of Medicine.
Previous work by the same research team revealed that NS/PCs injected into non-injury sites by intravenous or intrathecal methods did not graft in sufficient numbers, but often became "trapped" in the lungs and kidneys.
They concluded that intralesion application might be the most effective and reliable method for transplanting NS/PCs.
This study, also using laboratory mice with SCI, sought to determine how effective intralesion injection might be. NS/PCs were obtained from transgenic mice for Venus and luciferase fusion protein, which allowed the cells to be tracked by bioluminescence imaging (BLI) after transplant.
"Wild-type [normal] mice were given a spinal cord injury at the T10 level," explained Dr. Nakamura.
"Low and high doses of NS/PCs derived from fetal transgenic mice were injected into four groups of mice at either the:
1) lesion epicenter [site of injury] (E)
2) rostral (head) and caudal (tail) sites (RC) with neural stem - progenitor cells derived from fetal transgenic mice
3) while a fifth group of controls [untreated] was injected with phosphate buffered saline at E [lesion epicenter or site of injury]."
All four groups of mice receiving the cells experienced motor functional recovery while those in the control group did not. They also found that the photon counts from BLI of the grafted NS/PCs were similar in each of the four transplantation groups.
"This suggests that the survival of the NS/PCs was fairly uniform when more than a certain threshold number of cells were transplanted," said researchers.
"However, analysis showed that brain-derived neurotropic factor expression was higher in the RC [head and tail] segment than in the E [site of injury] segment."
This result may explain why transplanted NS/PCs appear to differentiate more readily into neurons than astrocytes in the RC group due to enhanced expression of brain-derived neurotrophic factor.
"This may mean that the microenvironments of the site of injury and head and tail sites are similarly able to support neural stem/progenitor cells transplanted during the sub-acute phase of spinal cord injury (SCI)."
"This study provides evidence that the lesion microenvironment can support cell survival. The next step is to determine factors that will impact favorably on the optimization of the cell transplantation site," Dr. John Sladek, Cell Transplantation section editor and professor of neurology and pediatrics at the University of Colorado School of Medicine.
Transplantation of neural stem/progenitor cells (NS/PCs) promotes functional recovery after spinal cord injury (SCI); however, few studies have examined the optimal site of NS/PC transplantation in the spinal cord. The purpose of this study was to determine the optimal transplantation site of NS/PCs for the treatment of SCI. Wild-type mice were generated with contusive SCI at the T10 level and NS/PCs were derived from fetal transgenic mice. These NS/PCs ubiquitously expressed ffLuc-cp156 protein (Venus and luciferase fusion protein) and so could be detected by in vivobioluminescence imaging 9 days post-injury. NS/PCs (Low: 250,000 cells per mouse; High: 1 million cells per mouse) were grafted into the spinal cord at the lesion epicenter (E) or at rostral and caudal (RC) sites. Phosphate buffered saline was injected into E as a control. Motor functional recovery was better in each of the transplantation groups (Low-E, High-E,Low-RC and High-RC) than in the control group. The photon counts of the grafted NS/PCs were similar in each of the four transplantation groups, suggesting that the survival of NS/PCs was fairly uniform when more than a certain threshold number of cells were transplanted. Quantitative RT-PCR analyses demonstrated that brain-derived neurotropic factor expression was higher in the RC segment thanin the E segment, and this may underlie why NS/PCs more readily differentiated into neurons than into astrocytes in the RC group. The location of the transplantation site did not affect the area of spared fibers, angiogenesis, or the expression of any other mediators. These findings indicated that the microenvironments of the E and RC sites are able to support NS/PCs transplanted during the sub-acutephase of SCI similarly. Optimally, a certain threshold number of NS/PCs should be grafted into the E segment to avoid damaging sites adjacent to the lesion during the injection procedure.