2024-03-28T20:03:34Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/2142372021-12-28T15:57:43Zcom_10261_11773com_10261_1col_10261_11774
DIGITAL.CSIC
author
Mangin, Gabrielle
author
Cogo, Adrien
author
Moisan, Anaïck
author
Bonnin, Philippe
author
Maïer, Benjamin
author
Kubis, Nathalie
funder
European Commission
2020-06-12T11:44:55Z
2020-06-12T11:44:55Z
2019-07
Frontiers in Neuroscience 13: 718 (2019)
1662-4548
http://hdl.handle.net/10261/214237
10.3389/fnins.2019.00718
1662-453X
http://dx.doi.org/10.13039/501100000780
31379478
As the second cause of death and cognitive decline in industrialized countries, stroke is a major burden for society. Vascular risks factors such as hypertension and diabetes are involved in most stroke patients, aggravate stroke severity, but are still poorly taken into account in preclinical studies. Microangiopathy and sustained inflammation are exacerbated, likely explaining the severity of stroke in those patients. We sought to demonstrate that intravenous administration of human adipose derived-mesenchymal stem cells (hADMSC) that have immunomodulatory properties, could accelerate sensorimotor recovery, prevent long-term spatial memory impairment and promote neurogenesis, in diabetic or hypertensive mice, subjected to permanent middle cerebral artery occlusion (pMCAo). Diabetic (streptozotocin IP) or hypertensive (L-NAME in drinking water) male C57Bl6 mice subjected to pMCAo, were treated by hADMSC (500,000 cells IV) 2 days after cerebral ischemia induction. Infarct volume, neurogenesis, microglial/macrophage density, T-lymphocytes density, astrocytes density, and vessel density were monitored 7 days after cells injection and at 6 weeks. Neurological sensorimotor deficit and spatial memory were assessed until 6 weeks post-stroke. Whatever the vascular risk factor, hADMSC showed no effect on functional sensorimotor recovery or cognitive decline prevention at short or long-term assessment, nor significantly modified neurogenesis, microglial/macrophage, T-lymphocytes, astrocytes, and vessel density. This work is part of a European program (H2020, RESSTORE). We discuss the discrepancy of our results with those obtained in rats and the optimal cell injection time frame, source and type of cells according to the species stroke model. A comprehensive understanding of the mechanisms preventing recovery should help for successful clinical translation, but first could allow identifying good and bad responders to cell therapy in stroke.
openAccess
Stroke
Cell therapies
Adipose tissue
Cognitive decline
Inflammation
Behaviour
Intravenous Administration of Human Adipose Derived-Mesenchymal Stem Cells Is Not Efficient in Diabetic or Hypertensive Mice Subjected to Focal Cerebral Ischemia
artículo
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URL
https://digital.csic.es/bitstream/10261/214237/1/Intravenous_Mangin_Art2019.pdf
File
MD5
07aaf5de3b4014a7ae4d8f0cd6470553
2909404
application/pdf
Intravenous_Mangin_Art2019.pdf