RT Journal Article
SR Electronic
T1 Exogenous Neural Precursor Cell Transplantation Results in Structural and Functional Recovery in a Hypoxic-Ischemic Hemiplegic Mouse Model
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0369-18.2018
DO 10.1523/ENEURO.0369-18.2018
A1 Prakasham Rumajogee
A1 Svetlana Altamentova
A1 Lijun Li
A1 Junyi Li
A1 Jian Wang
A1 Alan Kuurstra
A1 Stephanie Beldick
A1 Ravi S. Menon
A1 Derek Van Der Kooy
A1 Michael G. Fehlings
YR 2018
UL http://www.eneuro.org/content/early/2018/10/22/ENEURO.0369-18.2018.abstract
AB Cerebral palsy (CP) is a common pediatric neurodevelopmental disorder, frequently resulting in motor and developmental deficits and often accompanied by cognitive impairments. A regular pathobiological hallmark of CP is oligodendrocyte maturation impairment resulting in white matter (WM) injury and reduced axonal myelination. Regeneration therapies based on cell replacement are currently limited, but neural precursor cells (NPCs), as cellular support for myelination, represent a promising regeneration strategy to treat CP, although the transplantation parameters (e.g. timing, dosage, mechanisms) remain to be determined.We optimised a hemiplegic mouse model of neonatal hypoxia-ischemia that mirrors the pathobiological hallmarks of CP and transplanted NPCs into the corpus callosum (CC), a major white matter structure impacted in CP patients. The NPCs survived, engrafted and differentiated morphologically in male and female mice. Histology and MRI showed repair of lesioned structures. Furthermore, electrophysiology revealed functional myelination of the CC (e.g. restoration of conduction velocity), while Cylinder and CatWalk tests demonstrated motor recovery of the affected forelimb. Endogenous oligodendrocytes, recruited in the CC following transplantation of exogenous NPCs, are the principal actors in this recovery process.The lack of differentiation of the transplanted NPCs is consistent with enhanced recovery due to an indirect mechanism, such as a trophic and/or a “bio-bridge” support mediated by endogenous oligodendrocytes. Our work establishes that transplantation of NPCs represents a viable therapeutic strategy for CP treatment, and that the enhanced recovery is mediated by endogenous oligodendrocytes. This will further our understanding and contribute to the improvement of cellular therapeutic strategies.SIGNIFICANCE STATEMENT Cerebral palsy (CP) is one of the most common pediatric neurodevelopmental disorders, affecting more than 17 million people worldwide. Current treatment options for CP are largely restricted to rehabilitative approaches that alleviate and mitigate symptoms.