Treatment of TBI with collagen scaffolds and human marrow stromal cells increases the expression of tissue plasminogen activator

This study examines the effects of combination therapy of collagen scaffolds and human marrow stromal cells (hMSCs) on the expression of tissue plasminogen activator (tPA) after traumatic brain injury (TBI) in rats. Adult male Wistar rats (n=48) were injured with controlled cortical impact and treat...

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Bibliographic Details
Published in:	Journal of neurotrauma Vol. 28; no. 7; p. 1199
Main Authors:	Mahmood, Asim, Qu, Changsheng, Ning, Riuzuo, Wu, Hongtao, Goussev, Anton, Xiong, Ye, Irtenkauf, Susan, Li, Yi, Chopp, Michael
Format:	Journal Article
Language:	English
Published:	United States 01-07-2011
Subjects:	Animals Bone Marrow Cells - cytology Bone Marrow Cells - metabolism Bone Marrow Transplantation - methods Brain Injuries - metabolism Brain Injuries - pathology Brain Injuries - surgery Collagen - physiology Collagen - therapeutic use Combined Modality Therapy - methods Disease Models, Animal Gene Expression Regulation - physiology Humans Male Rats Rats, Wistar Stromal Cells - cytology Stromal Cells - metabolism Stromal Cells - transplantation Tissue Plasminogen Activator - biosynthesis Tissue Plasminogen Activator - genetics Tissue Plasminogen Activator - secretion Tissue Scaffolds Transplantation, Heterologous - methods Transplantation, Heterologous - pathology
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Summary:	This study examines the effects of combination therapy of collagen scaffolds and human marrow stromal cells (hMSCs) on the expression of tissue plasminogen activator (tPA) after traumatic brain injury (TBI) in rats. Adult male Wistar rats (n=48) were injured with controlled cortical impact and treated either with scaffolds suffused with hMSCs (3×10(6)) or hMSCs (3×10(6)) alone transplanted into the lesion cavity 1 week after TBI. A control group was treated with saline. Neurological function was assessed using the Morris Water Maze test (MWM) and modified Neurological Severity Scores (mNSS). The rats were sacrificed 14 days after TBI and brain samples were processed for immunohistochemical analysis and quantitative Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) studies. Enhanced functional improvement was observed on both the mNSS and MWM tests in the scaffold+hMSC-treated group compared to the other two groups. Immunostaining with anti-human mitochondrial antibody (E5204) showed more hMSCs in the injury zone of the scaffold+hMSC group compared to the hMSC-alone group. Triple staining showed that more neurons were tPA-positive in the scaffold+hMSC group compared to the other two groups (p<0.05). Western blot analysis and qRT-PCR showed that scaffold+hMSC and hMSC-alone treatment enhanced the expression of tPA compared to controls (p<0.05), but tPA expression was significantly greater in the scaffold+hMSC group. The induction of tPA by hMSCs after TBI may be one of the mechanisms involved in promoting functional improvement after TBI.
ISSN:	1557-9042
DOI:	10.1089/neu.2010.1694