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.

specific adult stem cell may need to be expanded. Accordingly, adult stem cells may not only act locally in the tissues in which they reside, but may also be recruited out of the circulation and enlisted in regeneration of diverse tissues at distal sites. Taken to an extreme,

We show here that cells within human adult bone marrow can contribute to cells in the adult human brain. Cerebellar tissues from female patients with hematologic malignancies, who had received chemotherapy, radiation, and a bone marrow transplant, were analyzed. Brain samples were obtained at autopsy from female patients who received male (sex-mismatched) or female (sexmatched, control) bone marrow transplants. Cerebella were evaluated in 10-m-thick, formaldehyde-fixed, paraffin-embedded sections that encompassed up to Ϸ50% of a human Purkinje nucleus. A total of 5,860 Purkinje cells from sex-mismatched females and 3,202 Purkinje cells from sex-matched females were screened for Y chromosomes by epifluorescence. Confocal laser scanning microscopy allowed definitive identification of the sex chromosomes within the morphologically distinct Purkinje cells. In the brains of females who received male bone marrow, four Purkinje neurons were found that contained an X and a Y chromosome and two other Purkinje neurons contained more than a diploid number of sex chromosomes. No Y chromosomes were detected in the brains of sex-matched controls. The total frequency of male bone marrow contribution to female Purkinje cells approximated 0.1%. This study demonstrates that although during human development Purkinje neurons are no longer generated after birth, cells within the bone marrow can contribute to these CNS neurons even in adulthood. The underlying mechanism may be caused either by generation de novo of Purkinje neurons from bone marrow-derived cells or by fusion of marrow-derived cells with existing recipient Purkinje neurons.stem cell ͉ plasticity ͉ cell fusion ͉ cell fate change I n humans, bone marrow has been reported to contribute to human epithelium and liver, but not to the brain (1, 2). Here we investigated whether bone marrow-derived cells could cross the blood-brain barrier and contribute to neurons in the CNS. Previous studies in mice have shown that bone marrow-derived cells can contribute to neuronal cell types in the CNS, including a class of highly specialized neurons in the brain, the Purkinje neurons (3-5).Purkinje neurons are generated only during early brain development. In humans, generation of Purkinje neurons starts at 16 weeks of gestation and is complete by the end of the 23rd week (6). Most of the maturation of the characteristic dendritic trees of human Purkinje neurons is finalized during the first year of life (7). By contrast to other neurons in the adult brain, there is no evidence for the generation of new Purkinje neurons after birth, even in cases of severe Purkinje cell loss caused by trauma or genetic disease (8, 9).The human brain contains Ϸ15 million Purkinje cells, which are among the largest neurons in the CNS (10). A typical Purkinje neuron has Ͼ50-fold the volume of neighboring neurons in the brain, and its complex dendritic extensions receive inputs from as many as one million granule cells. Purkinje cells play vital roles in maintaining balance and regulating movement. A loss o...

Cells from adult bone marrow participate in the regeneration of damaged skeletal myofibers. However, the relationship of these cells with the various hematopoietic and nonhematopoietic cell types found in bone marrow is still unclear. Here we show that the progeny of a single cell can both reconstitute the hematopoietic system and contribute to muscle regeneration. Integration of bone marrow cells into myofibers occurs spontaneously at low frequency and increases with muscle damage. Thus, classically defined single hematopoietic stem cells can give rise to both blood and muscle.