title: Intravenous transplants of human adipose-derived stem cell protect the brain from traumatic brain injury-induced neurodegeneration and motor and cognitive impairments: cell graft biodistribution and soluble factors in young and aged rats.
abstract: Traumatic brain injury (TBI) survivors exhibit motor and cognitive symptoms from the primary injury that can become aggravated over time because of secondary cell death. In the present in vivo study, we examined the beneficial effects of human adipose-derived stem cells (hADSCs) in a controlled cortical impact model of mild TBI using young (6 months) and aged (20 months) F344 rats. Animals were transplanted intravenously with 4 × 10(6) hADSCs (Tx), conditioned media (CM), or vehicle (unconditioned media) at 3 h after TBI. Significant amelioration of motor and cognitive functions was revealed in young, but not aged, Tx and CM groups. Fluorescent imaging in vivo and ex vivo revealed 1,1' dioactadecyl-3-3-3',3'-tetramethylindotricarbocyanine iodide-labeled hADSCs in peripheral organs and brain after TBI. Spatiotemporal deposition of hADSCs differed between young and aged rats, most notably reduced migration to the aged spleen. Significant reduction in cortical damage and hippocampal cell loss was observed in both Tx and CM groups in young rats, whereas less neuroprotection was detected in the aged rats and mainly in the Tx group but not the CM group. CM harvested from hADSCs with silencing of either NEAT1 (nuclear enriched abundant transcript 1) or MALAT1 (metastasis associated lung adenocarcinoma transcript 1), long noncoding RNAs (lncRNAs) known to play a role in gene expression, lost the efficacy in our model. Altogether, hADSCs are promising therapeutic cells for TBI, and lncRNAs in the secretome is an important mechanism of cell therapy. Furthermore, hADSCs showed reduced efficacy in aged rats, which may in part result from decreased homing of the cells to the spleen.
authors.affiliation: Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair and School of Physical Therapy and Rehabilitation Sciences, University of South Florida Morsani College of Medicine, Tampa, Florida 33612, James A. Haley Veterans Affairs Hospital, Research Service, Tampa, Florida 33612, and Departments of Molecular Pharmacology and Physiology and Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida 33612.
authors.forename: Naoki
authors.initials: N
authors.lastname: Tajiri
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Acosta
authors.forename: Md
authors.initials: M
authors.lastname: Shahaduzzaman
authors.forename: Hiroto
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Shinozuka
authors.forename: Mibel
authors.initials: M
authors.lastname: Pabon
authors.forename: Diana
authors.initials: D
authors.lastname: Hernandez-Ontiveros
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Christopher
authors.initials: C
authors.lastname: Metcalf
authors.forename: Meaghan
authors.initials: M
authors.lastname: Staples
authors.forename: Travis
authors.initials: T
authors.lastname: Dailey
authors.forename: Julie
authors.initials: J
authors.lastname: Vasconcellos
authors.forename: Giorgio
authors.initials: G
authors.lastname: Franyuti
authors.forename: Lisa
authors.initials: L
authors.lastname: Gould
authors.forename: Niketa
authors.initials: N
authors.lastname: Patel
authors.forename: Denise
authors.initials: D
authors.lastname: Cooper
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Cesar V
authors.initials: CV
authors.lastname: Borlongan
authors.forename: Paula C
authors.initials: PC
authors.lastname: Bickford
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000637:transplantation*; D000367:Age Factors; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D019957:Motor Skills Disorders / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D051381:Rats; D011916:Rats, Inbred F344; D033581:Stem Cell Transplantation / Q000379:methods*; D014018:Tissue Distribution / Q000502:physiology
keywords: aging; brain injury; stem cell