From Marrow to Brain: Expression of Neuronal Phenotypes in Adult Mice

Abstract

After intravascular delivery of genetically marked adult mouse bone marrow into lethally irradiated normal adult hosts, donor-derived cells expressing neuronal proteins (neuronal phenotypes) developed in the central nervous system. Flow cytometry revealed a population of donor-derived cells in the brain with characteristics distinct from bone marrow. Confocal microscopy of individual cells showed that hundreds of marrow-derived cells in brain sections expressed gene products typical of neurons (NeuN, 200-kilodalton neurofilament, and class III beta-tubulin) and were able to activate the transcription factor cAMP response element-binding protein (CREB). The generation of neuronal phenotypes in the adult brain 1 to 6 months after an adult bone marrow transplant demonstrates a remarkable plasticity of adult tissues with potential clinical applications.

Human Bone Marrow Stem Cells Exhibit Neural Phenotypes and Ameliorate Neurological Deficits after Grafting into the Ischemic Brain of Rats

“…Previous in vivo studies have examined the differentiation of murine MSC. Transplantation of murine MSCs gave rise to neurons (8,29,35) and astrocytes (29). Two recent reports have shown that human MSCs could differentiate in vitro into neurons (49,57) and astrocytes (49).…”

“…Bone marrow stromal cells or mesenchymal stem cells (MSCs) not only give rise to mesodermal lineage cells such as osteoblasts, chondrocytes, adipocytes, and muscle cells (4,13,29,55,33), but also adopt neuroectodermal cell fate. It has been shown that donor-derived neurons and astrocytes are found in host rodent brain following transplantation of rodent bone marrow (8,14,29,35). However, it is not known if transplantation of MSCs into the brain can be beneficial in treating neurological disorders.…”

Migration, fate and in vivo imaging of adult stem cells in the CNS

“…In some studies, they differentiated in vivo into astrocytes and even neurons. 47,48 Human MSCs were injected into rats after middle cerebral artery occlusion. 49,50 In both studies, implanted cells reduced the lesion volume and elicited functional improvement compared with the control sham group.…”

Adult bone marrow–derived stem cells for organ regeneration and repair

“…Ongoing efforts in regenerative medicine have focused on this regeneration dilemma when using bone marrow as a source of cells that facilitate repair of injured organs without causing detrimental tissue reactions. Since it was shown that bone marrowderived cells can give rise to myocytes (Ferrari et al, 1998), hepatocytes (Petersen et al, 1999), endothelial and myocardial cells (Lin et al, 2000;Orlic et al, 2001a), neuronal and glial cells (Brazelton et al, 2000;Mezey et al, 2000), and a number of other cell types (Krause et al, 2001), bone marrow-derived cells arte currently the preferred cell type used in regenerative medicine. A number of problems with these studies, including the lack of functional characterization of "switched cells," the mixed population of utilized donor cells used, and cell fusion, have been largely ignored.…”