Mesenchymal stem cells promote proliferation of endogenous neural stem cells and survival of newborn cells in a rat stroke model

TLDR

Mesenchymal stem cells secrete bioactive factors that elicit diverse responses in vivo. The study investigates how MSCs might enhance functional recovery in a rat stroke model. Bone marrow‑derived MSCs were transplanted into the brain parenchyma 3 days after middle cerebral artery occlusion, and stroke induced proliferation of resident neural stem cells in the subventricular zone. MSC transplantation increased endogenous neural stem cell proliferation, reduced newborn cell death, promoted migration and differentiation into doublecortin⁺ neuroblasts in ischemic areas, and thus partly explains the improved functional recovery and supports clinical potential.

Abstract

Mesenchymal stem cells (MSCs) secrete bioactive factors that exert diverse responses in vivo. In the present study, we explored mechanism how MSCs may lead to higher functional recovery in the animal stroke model. Bone marrow-derived MSCs were transplanted into the brain parenchyma 3 days after induction of stroke by occluding middle cerebral artery for 2 h. Stoke induced proliferation of resident neural stem cells in subventricular zone. However, most of new born cells underwent cell death and had a limited impact on functional recovery after stroke. Transplantation of MSCs enhanced proliferation of endogenous neural stem cells while suppressing the cell death of newly generated cells. Thereby, newborn cells migrated toward ischemic territory and differentiated in ischemic boundaries into doublecortin+ neuroblasts at higher rates in animals with MSCs compared to control group. The present study indicates that therapeutic effects of MSCs are at least partly ascribed to dual functions of MSCs by enhancing endogenous neurogenesis and protecting newborn cells from deleterious environment. The results reinforce the prospects of clinical application using MSCs in the treatment of neurological disorders.