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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurosci. | doi: 10.3389/fnins.2019.00718

Intravenous administration of human adipose derived-mesenchymal stem cells is not efficient in diabetic or hypertensive mice subjected to focal cerebral ischemia

 Gabrielle Mangin1, Adrien Cogo2, Anaick Moisan3,  Philippe Bonnin2,  Benjamin MAIER1 and  Nathalie Kubis2, 4*
  • 1INSERM U965 Carcinose Angiogenèse et Recherche Translationnelle, France
  • 2INSERM U1148 Laboratoire de Recherche Vasculaire Translationnelle, France
  • 3Etablissement Français du Sang Auvergne Rhône-Alpes, France
  • 4Université Paris-Sorbonne, France

As the third 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 and promote neurogenesis, in diabetic or hypertensive mice subjected to permanent middle cerebral artery occlusion (pMCAo). Diabetic (streptozotocin IP) or hypertensive (L-NAME per os) male C57Bl6 mice subjected to pMCAo, were treated by hADMSC (500,000 cells IV) 2 days post stroke. 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 six weeks post stroke. Whatever the vascular risk factor, hADMSC showed no effect on functional recovery/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 importance of timing, source and type of cells according to the species that is considered. 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.

Keywords: cell therapy, Adipose Tissue, post-stroke dementia, Post-stroke inflammation, diabetes, Hypertension

Received: 06 Apr 2019; Accepted: 26 Jun 2019.

Edited by:

Johannes Boltze, University of Warwick, United Kingdom

Reviewed by:

Jan-Kolja Strecker, University of Münster, Germany
Andrew N. Clarkson, University of Otago, New Zealand
Alison Willing, University of South Florida, United States  

Copyright: © 2019 Mangin, Cogo, Moisan, Bonnin, MAIER and Kubis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Nathalie Kubis, Université Paris-Sorbonne, Paris, France, nathalie.kubis@aphp.fr