Neural precursor cells can be delivered into the injured cervical spinal cord by intrathecal injection at the lumbar cord.
Neural precursor cells (NPCs) are promising grafts for treatment of traumatic CNS injury and neurodegenerative disorders because of their potential to differentiate into neurons and glial cells. When designing clinical protocols for NPC transplantation, it is important to develop alternatives to direct parenchymal injection, particularly at the injury site. We reasoned that since it is minimally invasive, intrathecal delivery of NPCs at lumbar spinal cord (lumbar puncture) represents an important and clinically applicable strategy. We tested this proposition by examining whether NPCs can be delivered to the injured cervical spinal cord via lumbar puncture using a mixed population of neuronal-restricted precursors (NRPs) and glial-restricted precursors (GRPs). For reliable tracking, the NPCs were derived from the embryonic spinal cord of transgenic donor rats that express the marker gene, human placental alkaline phosphatase, under the control of the ubiquitous Rosa 26 promoter. We found that mixed NRP/GRP grafts can be efficiently delivered to a cervical hemisection injury site by intrathecal delivery at the lumbar cord. Similar to direct parenchymal injections, transplanted NRP/GRP cells survive at the injury cavity for at least 5 weeks post-engraftment, migrate into intact spinal cord along white matter tracts and differentiate into all three mature CNS cell types, neurons, astrocytes, and oligodendrocytes. Furthermore, very few graft-derived cells localize to areas outside the injury site, including intact spinal cord and brain. These results demonstrate the potential of delivering lineage-restricted NPCs using the minimally invasive lumbar puncture method for the treatment of spinal cord injury.
Lepore
Angelo C
AC
Department of Neurobiology and Anatomy, 2900 Queen Lane, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Bakshi
Ajay
A
Swanger
Sharon A
SA
Rao
Mahendra S
MS
Fischer
Itzhak
I
D000469:Alkaline Phosphatase; D000818:Animals; D030801:Animals, Genetically Modified; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D058851:GPI-Linked Proteins; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D007278:Injections, Spinal / Q000379:methods; D007527:Isoenzymes / Q000235:genetics; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000628:therapy*; D013129:Spinal Puncture / Q000379:methods; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000502:physiology*; D016896:Treatment Outcome
D015415:Biomarkers; D058851:GPI-Linked Proteins; D007527:Isoenzymes; D000469:Alkaline Phosphatase; C019839:alkaline phosphatase, placental