title: Treatment of TBI with collagen scaffolds and human marrow stromal cells increases the expression of tissue plasminogen activator.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Henry Ford Health System, 2799 West Grand Boulevard, Detroit, MI 48202, USA. nsaam@neuro.hfh.edu
authors.forename: Asim
authors.initials: A
authors.lastname: Mahmood
authors.forename: Changsheng
authors.initials: C
authors.lastname: Qu
authors.forename: Riuzuo
authors.initials: R
authors.lastname: Ning
authors.forename: Hongtao
authors.initials: H
authors.lastname: Wu
authors.forename: Anton
authors.initials: A
authors.lastname: Goussev
authors.forename: Ye
authors.initials: Y
authors.lastname: Xiong
authors.forename: Susan
authors.initials: S
authors.lastname: Irtenkauf
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D016026:Bone Marrow Transplantation / Q000379:methods*; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D003094:Collagen / Q000502:physiology* / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000379:methods; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D054457:Tissue Scaffolds; D014183:Transplantation, Heterologous / Q000379:methods / Q000473:pathology
chemical_list: D003094:Collagen; D010959:Tissue Plasminogen Activator