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

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 cort...

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Published in:The Journal of neuroscience 2014-01, Vol.34 (1), p.313-326
Main Authors: Tajiri, Naoki, Acosta, Sandra A, Shahaduzzaman, Md, Ishikawa, Hiroto, Shinozuka, Kazutaka, Pabon, Mibel, Hernandez-Ontiveros, Diana, Kim, Dae Won, Metcalf, Christopher, Staples, Meaghan, Dailey, Travis, Vasconcellos, Julie, Franyuti, Giorgio, Gould, Lisa, Patel, Niketa, Cooper, Denise, Kaneko, Yuji, Borlongan, Cesar V, Bickford, Paula C
Format: Article
Language:English
Subjects:
Adipose Tissue - cytology
Adipose Tissue - transplantation
Age Factors
Animals
Brain - metabolism
Brain - pathology
Brain - surgery
Brain Injuries - metabolism
Brain Injuries - pathology
Brain Injuries - surgery
Cells, Cultured
Cognition Disorders - metabolism
Cognition Disorders - pathology
Cognition Disorders - surgery
Humans
Infusions, Intravenous
Male
Motor Skills Disorders - metabolism
Motor Skills Disorders - pathology
Motor Skills Disorders - surgery
Nerve Degeneration - metabolism
Nerve Degeneration - pathology
Nerve Degeneration - surgery
Rats
Rats, Inbred F344
Stem Cell Transplantation - methods
Tissue Distribution - physiology
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Summary: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.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.2425-13.2014