Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats

We tested the hypothesis that bone marrow stromal cells (MSCs) transplanted into the ischemic boundary zone, survive, differentiate and improve functi onal recovery after middle cerebral artery occlusion (MCAo). MSCs were harv ested from adult rats and cultured with or without nerve growth factor (NGF ). For cellular identification, MSCs were prelabeled with bromodeoxyuridine (BrdU). Rats (n = 24) were subjected to 2 h of MCAo, received grafts at 24 h and were euthanized at 14 days after MCAo. Test groups consisted of: (1) control-MCAo alone (n = 8); (2) intracerebral transplantation of MSCs (n = 8); (3) intracerebral transplantation of MSCs cultured with NGF (n = 8). I mmunohistochemistry was used to identify cells from MSCs. Behavioral tests (rotarod, adhesive-removal and modified neurological severity score [NSS]) were performed before and after MCAo. The data demonstrate that MSCs surviv e, migrate and differentiate into phenotypic neural cells. Significant reco very of somatosensory behavior (p < 0.05) and NSS (p < 0.05) were found in animals transplanted with MSCs compared with control animals. Animals that received MSCs cultured with NGF displayed significant recovery in motor (p < 0.05), somatosensory (p < 0.05) and NSS (p < 0.05) behavioral tests compa red with control animals. Our data suggest that intracerebral transplantati on of MSCs may provide a powerful autoplastic therapy for stroke. (C) 2001 Elsevier Science B.V. All rights reserved.