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Grafted neural progenitors migrate and form neurons after experimental traumatic brain injury
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. (Karin Forsberg Nilsson)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. (Lars Hillered)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
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2009 (English)In: Restorative Neurology and Neuroscience, ISSN 0922-6028, Vol. 27, no 4, 323-334 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Amsterdam: IOS Press , 2009. Vol. 27, no 4, 323-334 p.
Keyword [en]
TBI, EGFP transgenic mice, transplantation, migration, regeneration, neural stem cells, CNS
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-110090DOI: 10.3233/RNN-2009-0481ISI: 000269629700007PubMedID: 19738325OAI: oai:DiVA.org:uu-110090DiVA: diva2:275182
Available from: 2009-11-03 Created: 2009-11-03 Last updated: 2014-10-03Bibliographically approved
In thesis
1. Neural Stem and Progenitor Cells as a Tool for Tissue Regeneration
Open this publication in new window or tab >>Neural Stem and Progenitor Cells as a Tool for Tissue Regeneration
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Neural stem and progenitor cells (NSPC) can differentiate to neurons and glial cells. NSPC are easily propagated in vitro and are therefore an attractive tool for tissue regeneration. Traumatic brain injury (TBI) is a common cause for death and disabilities. A fundamental problem following TBI is tissue loss. Animal studies aiming at cell replacement have encountered difficulties in achieving sufficient graft survival and differentiation. To improve outcome of grafted cells after experimental TBI (controlled cortical impact, CCI) in mice, we compared two transplantation settings. NSPC were transplanted either directly upon CCI to the injured parenchyma, or one week after injury to the contralateral ventricle. Enhanced survival of transplanted cells and differentiation were seen when cells were deposited in the ventricle. To further enhance cell survival, efforts were made to reduce the inflammatory response to TBI by administration of ibuprofen to mice that had been subjected to CCI. Inflammation was reduced, as monitored by a decrease in inflammatory markers. Cell survival as well as differentiation to early neuroblasts seemed to be improved.

To device a 3D system for future transplantation studies, NSPC from different ages were cultured in a hydrogel consisting of hyaluronan and collagen. Cells survived and proliferated in this culturing condition and the greatest neuronal differentiating ability was seen in cells from the newborn mouse brain.

NSPC were also used in a model of peripheral nervous system injury, and xeno-transplanted to rats where the dorsal root ganglion had been removed. Cells survived and differentiated to neurons and glia, furthermore demonstrating their usefulness as a tool for tissue regeneration.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 69 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 500
Keyword
traumatic brain injury, neural stem cells, transplantation, CNS, PNS, progenitor cells, inflammation, CCI
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Neurosurgery; Medical Biochemistry
Identifiers
urn:nbn:se:uu:diva-110095 (URN)978-91-554-7658-8 (ISBN)
Public defence
2009-12-17, B42, Husargatan 3, BMC, 09:15 (Swedish)
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Available from: 2009-11-26 Created: 2009-11-03 Last updated: 2009-11-26Bibliographically approved

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