Cell Transplant. 2016 Feb 26. [Epub ahead of print]

Intravenous injection of clinical grade human MSCs after experimental stroke: functional benefit and microvascular effect.

Moisan A, Favre I, Rome C, De Fraipont F, Grillon E, Coquery N, Mathieu H, Mayan V, Naegele B, Hommel M, Richard MJ, Barbier EL, Remy C, Detante O.

Abstract

Stroke is the leading cause of disability in adults. Many current clinical trials use an intravenous (IV) administration of human mesenchymal stromal/stem cells (hMSCs). This autologous graft requires a delay for ex vivo expansion of cells. We followed microvascular effects and mechanisms of action involved after an IV injection of hMSCs at a subacute phase of stroke. Rats underwent a transient middle cerebral artery occlusion (MCAo) or a surgery without occlusion (sham) at day 0 (D0). At D8, rats received an IV injection of 3 million hMSCs or PBSglutamine. In a longitudinal behavioral follow-up, we showed delayed somatosensory and cognitive benefits 4 to 7 weeks after hMSC injection. In a separate longitudinal in-vivo MRI study, we observed an enhanced vascular density in the ischemic area 2 and 3 weeks after hMSC injection. Histology and RT-qPCR enlighted an overexpression of angiogenic factors such as Ang1 and TGFß1 at D16 in hMSC-treated MCAo rats compared to PBS-treated MCAo rats. Altogether, delayed IV injection of hMSCs provides functional benefits and increases cerebral angiogenesis in the stroke lesion, via a release of endogenous angiogenic factors enhancing the stabilization of newborn vessels. An enhanced angiogenesis could therefore be a mean to improve functional recovery after stroke.