Male Donor-derived Cells in the Brains of Female Sex-mismatched Bone Marrow Transplant Recipients

Unger, Elizabeth R.; Sung, Joo Ho; Manivel, J. Carlos; Chenggis, Margie L.; Blazar, Bruce R.; Krivit, William

doi:10.1097/00005072-199309000-00004

Cited by 175 publications

(84 citation statements)

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“…Perivascular macrophages are monocyte lineage cells that sit on the ablumenal side of the vascular tube commonly found in the Virchow-Robin space, a small fluid filled canal that lines the ablumenal surface of the veins and arteries that enter/ leave the CNS (Hickey and Kimura 1988;Polfliet et al 2001). These cells are derived from bloodborne progenitors, and chimera experiments suggest that they are able to cross the BBB and can be 80% replaced within 3 mo (Unger et al 1993;Vass et al 1993;Williams et al 2001). These cells provide a first line of innate immunity by phagocytosing cellular debris.…”

Section: Basement Membranementioning

confidence: 99%

The Blood–Brain Barrier

Daneman

Prat

2015

Cold Spring Harb Perspect Biol

2,418

1,829

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Blood vessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood-brain barrier, which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and also protects the neural tissue from toxins and pathogens, and alterations of these barrier properties are an important component of pathology and progression of different neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the endothelial cells (ECs) that form the walls of the blood vessels, and these properties are regulated by interactions with different vascular, immune, and neural cells. Understanding how these different cell populations interact to regulate the barrier properties is essential for understanding how the brain functions during health and disease.

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Section: Basement Membranementioning

confidence: 99%

The Blood–Brain Barrier

Daneman

Prat

2015

Cold Spring Harb Perspect Biol

2,418

1,829

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“…The hypothesis that microglial cells are of hemopoietic origin has been tested in mammals using bone marrow chimeras (Matsumoto and Fujiwara, 1987;Hickey and Kimura, 1988;De Groot et al, 1992;Hickey et al, 1992;Unger et al, 1993;Krall et al, 1994). One of these studies (Matsumoto and Fujiwara, 1987) failed to observe microglial cells of bone marrow origin, and concluded that microglia were probably of neuroectodermal origin.…”

Section: Origin From Primitive Hemopoietic Cellsmentioning

confidence: 99%

The origin and differentiation of microglial cells during development

Cuadros

Navascués

1998

Progress in Neurobiology

269

177

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AbstractÐSome authors claim that microglia originate from the neuroepithelium, although most now believe that microglial cells are of mesodermal origin, and probably belong to the monocyte/macrophage cell line. These cells must enter the developing central nervous system (CNS) from the blood stream, the ventricular space or the meninges. Afterward microglial cells are distributed more or less homogeneously through the entire nervous parenchyma. Stereotyped patterns of migration have been recognized during development, in which long-distance tangential migration precedes radial migration of individual cells. Microglial cells moving through the nervous parenchyma are ameboid microglia, which apparently di erentiate into rami®ed microglia after reaching their de®nitive location. This is supported by the presence of cells showing intermediate features between those of ameboid and rami®ed microglia. The factors that control the invasion of the nervous parenchyma, migration within the developing CNS and di erentiation of microglial cells are not well known. These phenomena apparently depend on environmental factors such as soluble or cell-surface bound molecules and components of the extracellular matrix. Microglial cells within the developing CNS are involved in clearing cell debris and withdrawing misdirected or transitory axons, and presumably support cell survival and neurite growth. #

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“…In mice, transplantation of transduced bone marrow cells allows the expression of glucocerebrosidase or GFP in microglia (8,9). In humans, there are very little data documenting the fate of bone marrow-derived cells in the CNS after bone marrow transplantation (BMT) (10,11). However, that BMT is used to treat genetic CNS diseases like Hurler disease or X-linked adrenoleukodystrophy (ALD) (12,13) suggests that bone marrow cells may serve as vehicles for the delivery of genes into the human CNS.…”

mentioning

confidence: 99%

Human CD34⁺cells differentiate into microglia and express recombinant therapeutic protein

Asheuer

Pflumio

Benhamida

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

154

103

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In rodents, bone marrow-derived cells enter the brain during adult life. Allogeneic bone marrow transplantation is used to treat genetic CNS diseases, but the fate of human bone marrow and CD34 ؉ cells within the brain remains to be elucidated. The present study demonstrates that cells derived from human CD34 ؉ cells, isolated from either cord blood or peripheral blood, migrate into the brain after infusion into nonobese diabetic͞severe combined immunodeficient mice. Both types of CD34 ؉ -derived cells differentiate into perivascular and ramified microglia. The lentiviral transfer of genes into CD34 ؉ cells before infusion does not modify the differentiation of human CD34 ؉ cells into microglia, allowing new transgenic proteins to be expressed in these cells. The transplantation of CD34 ؉ cells could thus be used for the treatment of CNS diseases. U p to 20% of the total nonneuronal cell population is made of microglia (1). Microglia are ubiquitously distributed in the CNS and play a major role in the response to infectious, traumatic, inflammatory, and ischemic processes, as well as in degenerative CNS diseases, such as Alzheimer's disease, multiple sclerosis, or Parkinson's disease. The adult brain contains two subsets of microglia: the resting microglia, which ramify throughout the brain parenchyma, and the perivascular microglia, which resemble peripheral macrophages (1, 2).Following a long debate about their origin, microglia are now believed to be derived from bone marrow as liver, spleen, or lung macrophages (2). Murine bone marrow-derived cells enter the CNS and differentiate into microglia (3-5). In mice, the turnover of perivascular microglia reaches 30% 1 year after engraftment, whereas the turnover of ramified microglia is much slower (6, 7). However, the subset of bone marrow-derived cells that are the progenitors of microglia has not been characterized. In mice, transplantation of transduced bone marrow cells allows the expression of glucocerebrosidase or GFP in microglia (8, 9). In humans, there are very little data documenting the fate of bone marrow-derived cells in the CNS after bone marrow transplantation (BMT) (10, 11). However, that BMT is used to treat genetic CNS diseases like Hurler disease or X-linked adrenoleukodystrophy (ALD) (12, 13) suggests that bone marrow cells may serve as vehicles for the delivery of genes into the human CNS.Transplantation of CD34 ϩ hematopoietic cells is replacing that of whole bone marrow cells for many applications, including autotransplantation in cancer, non-HLA genoidentical BMT, and gene therapy (14-16). Human CD34 ϩ cells can be easily collected from cord blood at birth or from peripheral blood after cytokine mobilization. We studied the migration, differentiation, and distribution of human CD34 ϩ cells purified either from umbilical cord blood (UCB) or from mobilized peripheral blood (MPB) in the brain of nonobese diabetic͞severe combined immunodeficient (NOD͞SCID) mouse. Our results demonstrate that a fraction of these cells, when infused into NOD͞SCI...

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Male Donor-derived Cells in the Brains of Female Sex-mismatched Bone Marrow Transplant Recipients

Cited by 175 publications

References 0 publications

The Blood–Brain Barrier

The Blood–Brain Barrier

The origin and differentiation of microglial cells during development

Human CD34⁺cells differentiate into microglia and express recombinant therapeutic protein

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Male Donor-derived Cells in the Brains of Female Sex-mismatched Bone Marrow Transplant Recipients

Cited by 175 publications

References 0 publications

The Blood–Brain Barrier

The Blood–Brain Barrier

The origin and differentiation of microglial cells during development

Human CD34+cells differentiate into microglia and express recombinant therapeutic protein

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Product

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Human CD34⁺cells differentiate into microglia and express recombinant therapeutic protein