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Intralesional Transplantation of Matrix-Embeded Human Fetal Neural Stem Cell in Rat Model of Penetrating Traumatic Brain Injury (PTBI)

Investigator: Lee-Onn Chieng

Mentor: Ross Bullock, MD, PhD

PTBI has been associated with high mortality as well as severe cognitive and motor deficits. Currently, there is no neurorestorative therapy for PTBI. Experimental models of PTBI such as the “ penetrating ballistic brain injury” (PBBI) has shown ~15-25% engraftment of human NSC’s, but cell therapy needs to address the toxic microenvironment in the lesion core. The hypothesis of this study is that survival of human neural stem cell (hNSC) in the lesion core will be improved when they are embedded within a fibrin-matrix.

In our study, athymic Sprague-Dawley rats with unilateral PBBI were randomly assigned to groups:1) hNSC without matrix 2) hNSC with matrix. Stereotactic injection of control or fibrin-matrix embedded hNSCs into lesion core was carried out a week following PBBI. Animals were sacrificed at 2 weeks or 6 weeks endpoint. Immunohistochemistry staining and confocal microscopy was used to analyze survival, distribution, differentiation and potential tumor formation.

Histological analysis revealed cell survival and distribution in the group with fibrin scaffold and differentiation was greater than in the group without matrix at both time points post transplantation. The transplants seem to migrate into the lesion penumbra as well as extending processes to contralateral hemisphere through corpus callosum. The grafted cells were predominantly stained for immature neuronal but not astrocytic markers. In addition no abnormal aggregation of undifferentiated cells were observed in either groups.

In this model, we concluded that there was robust engraftment of FDA-approved hNSCs observed up to 6 weeks, suggesting that this injury is conducive for repair.

Last modified: 2/01/2017

Updated on February 3, 2017.

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