Affiliations: Department of Medical Biochemistry and Microbiology,
Uppsala University, Biomedical Center, Uppsala, Sweden | Department of Neuroscience, Neurosurgery, Uppsala
University Hospital, Uppsala, Sweden
Note: [] Corresponding author: Karin Forsberg-Nilsson, PhD, Department of
Medical Biochemistry and Microbiology, Box 582, Biomedical Center, 751 23
Uppsala, Sweden. Tel.: +46 18 471 41 58; Fax: +46 18 471 46 73; E-mail:
karin.nilsson@imbim.uu.se
Abstract: Purpose: Neural stem and progenitor cells (NSPC) generate neurons
and glia, a feature that makes them attractive for cell replacement therapies.
However, efforts to transplant neural progenitors in animal models of brain
injury typically result in high cell mortality and poor neuronal
differentiation. Methods: In an attempt to improve the outcome for grafted NSPC after
controlled cortical impact we transplanted Enhanced Green Fluorescent Protein
(EGFP)-positive NSPC into the contra lateral ventricle of mice one week after
injury. Results: Grafted EGFP-NSPC readily migrated to the injured
hemisphere where we analyzed the proportion of progenitors and differentiated
progeny at different time points. Transplantation directly into the injured
parenchyma, resulted in few brains with detectable EGFP-NSPC. On the contrary,
in more than 90% of the mice that received a transplant into the lateral
ventricle detectable EGFP-positive cells were found. The cells were integrated
into the lateral ventricle wall of the un-injured hemisphere, throughout the
corpus callosum, and in the cortical perilesional area. At one-week post
transplantation, grafted cells that had migrated to the perilesion area mainly
expressed markers of neural progenitors and neurons, while in the corpus
callosum and the ventricular lining, grafted cells with a glial fate were more
abundant. After 3 months, grafted cells in the perilesion area were less
abundant whereas cells that had migrated to the walls of the third- and
lateral- ventricle of the injured hemisphere were still detectable, suggesting
that the injury site remained a hostile environment. Conclusion: Transplantation to the lateral ventricle, presumably for
being a neurogenic region, provides a favorable environment improving the
outcome for grafted NSPC both in term of their appearance at the cortical site
of injury, and their acquisition of neural markers.
