title: Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats.
abstract: There is now evidence to suggest that bone marrow mesenchymal stem cells (MSCs) not only differentiate into mesodermal cells, but can also adopt the fate of endodermal and ectodermal cell types. In this study, we addressed the hypotheses that human MSCs can differentiate into neural cells when implanted in the brain and restore sensorimotor function after experimental stroke. Purified human MSCs were grafted into the cortex surrounding the area of infarction 1 week after cortical brain ischemia in rats. Two and 6 weeks after transplantation animals were assessed for sensorimotor function and then sacrificed for histological examination. Ischemic rats that received human MSCs exhibited significantly improved functional performance in limb placement test. Histological analyses revealed that transplanted human MSCs expressed markers for astrocytes (GFAP(+)), oligodendroglia (GalC(+)), and neurons (beta III(+), NF160(+), NF200(+), hNSE(+), and hNF70(+)). The morphological features of the grafted cells, however, were spherical in nature with few processes. Therefore, it is unlikely that the functional recovery observed by the ischemic rats with human MSC grafts was mediated by the integration of new "neuronal" cells into the circuitry of the host brain. The observed functional improvement might have been mediated by proteins secreted by transplanted hMSCs, which could have upregulated host brain plasticity in response to experimental stroke.
authors.affiliation: Department of Neurosurgery, University of Minnesota, 55455, USA.
authors.forename: Li-Ru
authors.initials: LR
authors.lastname: Zhao
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Duan
authors.forename: Morayma
authors.initials: M
authors.lastname: Reyes
authors.forename: C Dirk
authors.initials: CD
authors.lastname: Keene
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Verfaillie
authors.forename: Walter C
authors.initials: WC
authors.lastname: Low
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D002545:Brain Ischemia / Q000209:etiology / Q000628:therapy*; D002454:Cell Differentiation / Q000502:physiology; D002469:Cell Separation; D002478:Cells, Cultured; D002648:Child; D004195:Disease Models, Animal; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000637:transplantation*; D009473:Neuronal Plasticity; D051381:Rats; D011918:Rats, Inbred SHR; D020127:Recovery of Function; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology; D014183:Transplantation, Heterologous; D016896:Treatment Outcome