Stem cells downregulate the elevated levels of tissue plasminogen activator in rats after spinal cord injury.
We investigated the involvement of tPA after SCI in rats and effect of treatment with human umbilical cord blood derived stem cells. tPA expression and activity were determined in vivo after SCI in rats and in vitro in rat embryonic spinal neurons in response to injury with staurosporine, hydrogen peroxide and glutamate. The activity and/or expression of tPA increased after SCI and reached peak levels on day 21 post-SCI. Notably, the tPA mRNA activity was upregulated by 310-fold compared to controls on day 21 post-SCI. As expected, MBP expression is minimal at the time of peak tPA activity and vice versa. Implantation of hUCB after SCI resulted in the downregulation of elevated tPA activity/expression in vivo in rats as well as in vitro in spinal neurons. Our results demonstrated the involvement of tPA in the secondary pathogenesis after SCI as well as the therapeutic potential of hUCB.
Veeravalli
Krishna Kumar
KK
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL 61605, USA.
Dasari
Venkata Ramesh
VR
Tsung
Andrew J
AJ
Dinh
Dzung H
DH
Gujrati
Meena
M
Fassett
Dan
D
Rao
Jasti S
JS
D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D036101:Cord Blood Stem Cell Transplantation; D015536:Down-Regulation; D006801:Humans; D008297:Male; D009474:Neurons / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*; D013234:Stem Cells / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
D010959:Tissue Plasminogen Activator