Cranial grafting of stem cell-derived microvesicles improves cognition and reduces neuropathology in the irradiated brain

Autor: Sarah N. Benke, Amber R. Syage, Audrey L. Park, Nicole N. Chmielewski, Charles L. Limoli, Munjal M. Acharya, Vipan K. Parihar, Ning Ru, Barrett D. Allen, Vahan Martirosian, Janet E. Baulch, Erich Giedzinski
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Nude
dendritic complexity
Neocortex
Hippocampus
neuroinflammation
Neural Stem Cells
Genes
Reporter
Cell-Derived Microparticles
Stem Cell Research - Nonembryonic - Human
Medicine
2.1 Biological and endogenous factors
Brain Damage
Chronic
Aetiology
Cells
Cultured
Cancer
Multidisciplinary
Cultured
Microvesicle
Biological Sciences
Amygdala
Neural stem cell
Radiation Injuries
Experimental
Neurological
Heterografts
Brain Damage
Chronic
Microglia
Stem cell
microvesicles
Cells
Neuropathology
Neuroprotection
03 medical and health sciences
Rats
Nude
Experimental
Rare Diseases
Animals
Humans
radiation-induced cognitive dysfunction
Habituation
Psychophysiologic
Radiation Injuries
Reporter
Neuroinflammation
Psychophysiologic
Transplantation
business.industry
Neurosciences
Stem Cell Research
Microvesicles
Rats
Brain Disorders
Brain Cancer
030104 developmental biology
human neural stem cells
Genes
Habituation
Cranial Irradiation
business
Cognition Disorders
Neuroscience
Zdroj: Proceedings of the National Academy of Sciences of the United States of America, vol 113, iss 17
Baulch, JE; Acharya, MM; Allen, BD; Ru, N; Chmielewski, NN; Martirosian, V; et al.(2016). Cranial grafting of stem cell-derived microvesicles improves cognition and reduces neuropathology in the irradiated brain. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 113(17), 4836-4841. doi: 10.1073/pnas.1521668113. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/1187f13x
DOI: 10.1073/pnas.1521668113.
Popis: Cancer survivors face a variety of challenges as they cope with disease recurrence and a myriad of normal tissue complications brought on by radio- and chemotherapeutic treatment regimens. For patients subjected to cranial irradiation for the control of CNS malignancy, progressive and debilitating cognitive dysfunction remains a pressing unmet medical need. Although this problem has been recognized for decades, few if any satisfactory long-term solutions exist to resolve this serious unintended side effect of radiotherapy. Past work from our laboratory has demonstrated the neurocognitive benefits of human neural stem cell (hNSC) grafting in the irradiated brain, where intrahippocampal transplantation of hNSC ameliorated radiation-induced cognitive deficits. Using a similar strategy, we now provide, to our knowledge, the first evidence that cranial grafting of microvesicles secreted from hNSC affords similar neuroprotective phenotypes after head-only irradiation. Cortical- and hippocampal-based deficits found 1 mo after irradiation were completely resolved in animals cranially grafted with microvesicles. Microvesicle treatment was found to attenuate neuroinflammation and preserve host neuronal morphology in distinct regions of the brain. These data suggest that the neuroprotective properties of microvesicles act through a trophic support mechanism that reduces inflammation and preserves the structural integrity of the irradiated microenvironment.
Databáze: OpenAIRE
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