Mechanisms of MSC as a cellular therapy in stroke - clinical of an advanced therapy medicinal product
type: Dataset
description: Stroke is the leading cause of disability in adult. Less than 10% of patients can be treated with thrombolysis. Except rehabilitation, no effective treatment exists to improve functional recovery after the acute phase. Therefore, there is a wide need to develop an effective therapy applicable after several days or weeks following stroke. Using a multiparametric approach (microvascular MRI, analysis of angiogenic genes expression and behavioral study) in rat ischemic stroke model, we defined a transition stage (D3-D7) followed by a subacute phase (D7-D25) during post-stroke remodeling. These two phases represent an interesting target time-window for administration of pro-angiogenic therapies. Since 20 years, cell therapy, notably by human mesenchymal stem/stromal cells (hMSC), emerged as a “regenerative treatment” with threefold increase in clinical trial during the last 10 years. However, still limited data are available regarding the mechanisms by which hMSC benefit, especially at the subacute phase. We progressed in understanding the microvascular plasticity that occurs after an intravenous injection of hMSC in a rat model of transient focal cerebral ischemia. Our preclinical studies were carried out simultaneously with a phase II clinical trial that currently goes on in Grenoble (ISIS: Intravenous Stem Cells After Ischemic Stroke). We reported a sustained functional and cognitive long-term benefit of hMSC IV injected at the subacute stage correlated to an increase of angiogenesis. Ang2, Ang1, SDF-1 and TGFβ1, whose endogenous level tends to be overexpressed by hMSC, would enhance stabilization and survival of newborn vessels, accounting for benefit of these cells. As part of the hMSC development as an advanced therapy medicinal product, we realized an in vivo tumorigenicity assay and showed the absence of tumor development after hMSC injection. We also retrospectively analyzed hMSC produced for the phase II clinical trial. We confirmed the feasibility to produce …
landing page: https://theses.hal.science/tel-00849150
identifier: NNT: 2012GRENS033
keyword: accident-vasculaire-cerebral
keyword: advanced-therapy-medicinal-product
keyword: angiogenese
keyword: angiogenesis
keyword: cellules-souches
keyword: infoeu-reposemanticsdoctoralthesis
keyword: irm
keyword: medicament-de-therapie-innovante
keyword: mesenchymal-stem
keyword: microvascularisation
keyword: microvasculature
keyword: mri
keyword: sdvmheplife-sciences-q-biohuman-health-and-pathology
keyword: stroke
keyword: stromal-cells
keyword: stromales-mesenchymateuses
keyword: theses
issued: 2026-05-10T04:50:17.903042
modified: 2026-05-10T04:50:17.903100
language: fr
contact point: Organization
  fn: CCSD

test_moissonnage_selune
type: Agent

Mechanisms of MSC as a cellular therapy in stroke - clinical of an advanced therapy medicinal product
type: Distribution
format: HTML
access URL: https://theses.hal.science/tel-00849150
issued: 2026-05-10T04:50:17.916836
modified: 2026-05-10T04:50:17.879945