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Results for “brain microenvironment”

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PubMed1987

Quantitative study of microvessel ultrastructure in human peritumoral brain tissue. Evidence for a blood-brain barrier defect.

The form and function of blood vessels are determined by the cells that constitute their microenvironment. Brain tissue around tumors contains varying numbers of tumor cells that could influence local capillaries to lose their blood-brain barrier (BBB), as they do in the tumor itself. Microvascular permeability cannot be measured directly in humans but can be inferred from a knowledge of vessel ultrastructure. The authors have examined the vascular ultrastructure associated with the BBB in human peritumoral brain tissue for evidence of BBB compromise and to correlate BBB features with the cellular components of the vessel microenvironment. Light microscopic examination of brain tissue samples in patients with primary brain tumors showed that the tissue lying beyond the visible edge of the tumor ranged from essentially normal to grossly infiltrated with tumor cells. Although some of the vessels were structurally normal, the microvessels as a group had elongated junctional clefts (unfused regions) and an increase in the density of endothelial vesicles. Furthermore, the cleft index (the percentage of the junctional profile that is unfused) varied directly with the local cell density. A subpopulation of vessels enveloped by a layer of tumor cells was grossly abnormal. However, vessels that were not immediately invested by tumor cells also showed some abnormalities. It is concluded that tumor cells infiltrating peritumoral brain tissue cause blood vessels to take on some of the structural characteristics of leaky vessels. Since direct contact is not required, and since the degree of abnormality correlates with the number of tumor cells in the environment, the authors suggest that this inductive influence is exerted over a distance and is dependent on the concentration of the inducing factors.

Adult↗
PubMed1993

Microglial reaction in the rat cerebral cortex induced by cortical spreading depression.

The response of microglial cells to cortical spreading depression (CSD) was studied in rat brain by immunocytochemistry. CSD was elicited for one hour by the topical application of 4M potassium chloride solution and the microglial reaction examined immunocytochemically after 4, 16, 24 and 72 hours. CSD was sufficient to induce a microglial reaction throughout the cortex at 24 hours. Activated microglial cells furthermore showed a striking de-novo expression of major histocompatibility complex class II antigens. In contrast, no microglial reaction was observed in the cortex of sham-operated animals. This microglial reaction in response to CSD was not associated with histologically detectable neuronal damage. These results support the view that microglial cells are extremely sensitive to changes of the brain microenvironment. Their activation may be related to changes of ion homeostasis in the brain which are not sufficient to trigger neuronal injury.

Animals↗
PubMed1998

Antigen-dependent intrathecal antibody synthesis in the normal rat brain: tissue entry and local retention of antigen-specific B cells.

The intrathecal Ab response to Ag introduced into the normal brain has not been fully explored. Involvement of Ag-specific, peripheral B cells in an intrathecal response was studied using a normal rat model of Ag infusion through an indwelling cannula into defined brain sites, while maintaining a functionally intact blood-brain barrier. Specific Ab was detected in serum and cerebrospinal fluid. The intrathecal response is first detectable at day 14. Isoelectric focusing of cerebrospinal fluid reveals banding patterns consistent with local Ab production. To increase Ag-specific, circulating peripheral lymphocytes available for trafficking to Ag-stimulated brain and for enhancing intrathecal Ab synthesis, rats were preimmunized peripherally. Subsequently, Ag or saline (control) was infused through the cannula. Under this protocol, intrathecal synthesis is detectable earlier (day 5 postinfusion). Immunohistochemical studies at the infusion site assessed Ag-specific B cells, T cells, and activated APCs. Rats receiving peripheral preimmunization followed by Ag into caudate nucleus have far greater numbers of these cells, including plasma cells, within the infusion site compared with saline controls. Results confirm previous indirect evidence of intrathecal Ab synthesis in normal rat brain and provide the first direct evidence for B cell trafficking across normal brain barriers plus retention at the Ag deposition site. Our studies indicate that the normal brain microenvironment supports development of Ag-directed humoral immunity. We propose that immune privilege in normal brain is characterized by down-regulation of cell-mediated but not Ab immune responses within the central nervous system.

Animals↗
PubMed2026

Spatial analysis reveals the evolving organization of IDH-mutant glioma.

Adult diffuse gliomas are composed of malignant cell states interwoven with the non-malignant brain microenvironment. Here, we combine spatial transcriptomics and spatial proteomics of isocitrate dehydrogenase (IDH)-mutant gliomas to define organizational principles across histological grades. In low-grade tumors, spatial organization is shaped by underlying brain anatomy. We identify a functional white-gray matter junction that restricts cortical invasion and is associated with marked changes in tumor composition and cellular phenotypes. This junction is preferentially traversed by oligodendrocyte progenitor (OPC)-like malignant cells, suggesting a role in tumor expansion. In contrast, tumors with intermediate histological features are largely disorganized, with few recurring interactions between cancer cell states and microenvironmental cell types. In high-grade tumors, hypoxia-associated structure emerges, resembling IDH-wild-type glioblastoma. Together, these findings reveal two independent axes of spatial organization-from anatomy-driven structure in low-grade tumors to hypoxia-driven organization in high-grade tumors-and establish a framework linking tumor grade to recurrent spatial interactions.

Isocitrate Dehydrogenase↗
PubMed2005

[The choroid plexuses: a dynamic interface between the blood and the cerebrospinal fluid].

The choroid plexuses form one of the interfaces that control the brain microenvironment by regulating the exchanges between the blood and the central nervous system. They appear early during brain development. Originating from four different areas of the neural tube, they protrude into the ventricular system of the brain. The choroidal mechanisms involved in the control of brain homeostasis include the structural properties of the epithelial cells that restrict diffusional processes, as well as specific exchange and secretion mechanisms. In addition to the anatomical and histological organization of the choroidal tissue, this review describes the mechanism of cerebrospinal fluid secretion which is the most studied function of the choroid plexus. Experimental evidence for an implication of the choroid plexuses in neuroprotective mechanisms and in the supply of biologically active polypeptides to the brain are also reviewed.

Animals↗
PubMed1999

Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains.

Stem cells are a valuable resource for treating disease, but limited access to stem cells from tissues such as brain restricts their utility. Here, we injected marrow stromal cells (MSCs) into the lateral ventricle of neonatal mice and asked whether these multipotential mesenchymal progenitors from bone marrow can adopt neural cell fates when exposed to the brain microenvironment. By 12 days postinjection, MSCs migrated throughout the forebrain and cerebellum without disruption to the host brain architecture. Some MSCs within the striatum and the molecular layer of the hippocampus expressed glial fibrillary acidic protein and, therefore, differentiated into mature astrocytes. MSCs also populated neuron rich regions including the Islands of Calleja, the olfactory bulb, and the internal granular layer of the cerebellum. A large number of MSCs also were found within the external granular layer of the cerebellum. In addition, neurofilament positive donor cells were found within the reticular formation of the brain stem, suggesting that MSCs also may have differentiated into neurons. Therefore, MSCs are capable of producing differentiated progeny of a different dermal origin after implantation into neonatal mouse brains. These results suggest that MSCs are potentially useful as vectors for treating a variety of central nervous system disorders.

Adipocytes↗
PubMed1987

Brain surface invasion and metastasis of murine malignant melanoma variants.

Mouse B16 melanoma sublines were selected sequentially for their abilities to colonize brain meninges and leptomeninges of C57BL/6 mice. After 14 selections subline B16-B14b was established that formed significantly more brain tumor colonies than the parental B16 line. Examination of brains at various times after intravenous or intra-arterial injection of B16 cells by electron microscopy revealed that B14b melanoma cells lodged in small brain blood vessels, proliferated and invaded through vessel walls into brain parenchyma and also along small blood vessels at perivascular sites. Invasion into brain parenchyma was characterized by extension of melanoma cell filopodia resulting in fragmentation and sometimes enfulgment of glial and neural cells. Analysis of cell surface proteins of B16 melanoma sublines revealed increased exposure of a Mr approximately 90,000 glycoprotein on the high brain-colonizing cells. Antibodies against the Mr approximately 90,000 glycoprotein reacted with a variety of human melanoma cell lines and with some fetal and adult tissues, indicating that this melanoma-associated component is not species-, tumor- or tissue-specific. The glycoprotein could be a cell surface receptor important in the survival and growth properties of melanoma cells in brain microenvironments.

Animals↗
PubMed1997

Effects of photodynamic therapy on glioma spheroids.

The present study describes the sensitivity of glioma cells to a haematoporphyrin derivative (Photosan-3) under laser activation (argon-pumped dye laser). The effects of photodynamic therapy (PDT) on cell growth, directional migration and cell invasion were investigated on two human glioma cell lines (GaMg and U-251 Mg). The directional cell migration and spheroid growth was determined for both cell lines exposed to increasing laser energy output (15-35J/cm2) with concentrations of 5 and 7 micrograms/ml of Photosan-3. Both cell lines showed a dose-dependent migratory response to increasing laser irradiation, that was more prominent in the 7 micrograms/ml treatment group. This effect occurred during the first 4 days after drug exposure. Also, spheroids from both cell lines showed a drug and laser output energy dose-dependent inhibition of growth which became apparent after a lag period of 6 days. The lag period was characterized by a decreased growth rate as compared with the control group. During this period the outer cell layers of the spheroids fell apart. The remaining spheroid tissue was not able to migrate and to regrow when exposed to the highest laser energy outputs (30-35J/cm2, 5 and 7 micrograms/ml Photosan-3). These spheroids showed, however, the ability for invasion when confronted with normal brain cell aggregated in vivo. Light microscopic observations of co-cultures between tumour tissue and brain cell aggregates revealed a normal tumour morphology. This indicates that the remaining tumour cells were not dead and could be stimulated to invade the normal tissue when exposed to a normal brain microenvironment.

Adult↗
PubMed2004

Region-specific distribution of human immunodeficiency virus type 1 long terminal repeats containing specific configurations of CCAAT/enhancer-binding protein site II in brains derived from demented and nondemented patients.

Previous studies have shown that two CCAAT/enhancer binding protein (C/EBP) binding sites (sites I and II) within the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) are critically important for efficient virus replication within cells of the monocyte lineage, a primary cell type infected by HIV-1. Sequence variation at C/EBP sites I and II has been shown to alter the affinity of C/EBP factors to these sites. Specifically, sequence variation within C/EBP binding site II has been shown to alter binding of purified C/EBP beta protein and basal activity of the HIV-1 LTR. We have previously demonstrated that the C/EBP site II consensus cladeB (ConB) variant was highly conserved in brain- and peripheral blood-derived LTRs of individuals with advanced HIV-1 disease. Given these important observations, the regional distribution of LTRs containing the C/EBP site II ConB variant derived from brain tissues of patients with and without HIV-1-associated dementia (HIVD) was examined. A statistically significant difference was found in the distribution of LTRs containing the C/EBP site II ConB variant in brain regions derived from patients with and without HIVD. In addition, we have previously shown that LTRs containing C/EBP site II 4C and 6G variants (designated according to the position at which nucleotide change occurred relative to ConB, followed by the actual nucleotide found at the variant position) were only found in brain tissue of patients with HIVD. As an extension of these observations, the regional distribution of LTRs containing C/EBP site II 4C or 6G variants derived from the brains of patients with HIVD was examined and a statistically significant difference was observed. We have shown that LTRs containing a low-affinity C/EBP site II 4C variant accumulated in the cerebellum. LTRs containing the 4C site variant in conjunction with the consensus cladeB (ConB) site I exhibited the lowest basal LTR activity of any of the LTRs examined. These results suggest that LTRs containing the C/EBP site II 4C configuration may promote the establishment of a latent provirus in the cerebellum, a region of the HIVD brain that exhibits little viral gene expression. Furthermore, LTRs containing a high affinity C/EBP site II 6G variant accumulated in the mid-frontal gyrus, a site of highly productive replication. In addition, LTRs containing the C/EBP site II 6G variant with the ConB at site I exhibited the highest basal LTR activity. In conclusion, distinct LTR populations with specific C/EBP site II configurations were found in different neuroanatomical regions of the brain, potentially due to differences in the molecular architecture of the LTR, viral entry pathways, and/or brain microenvironments.

AIDS Dementia Complex↗
PubMed2000

Correlation of tight junction morphology with the expression of tight junction proteins in blood-brain barrier endothelial cells.

Endothelial cells of the blood-brain barrier form complex tight junctions, which are more frequently associated with the protoplasmic (P-face) than with the exocytoplasmic (E-face) membrane leaflet. The association of tight junctional particles with either membrane leaflet is a result of the expression of various claudins, which are transmembrane constituents of tight junction strands. Mammalian brain endothelial tight junctions exhibit an almost balanced distribution of particles and lose this morphology and barrier function in vitro. Since it was shown that the brain endothelial tight junctions of submammalian species form P-face-associated tight junctions of the epithelial type, the question of which molecular composition underlies the morphological differences and how do these brain endothelial cells behave in vitro arose. Therefore, rat and chicken brain endothelial cells were investigated for the expression of junctional proteins in vivo and in vitro and for the morphology of the tight junctions. In order to visualize morphological differences, the complexity and the P-face association of tight junctions were quantified. Rat and chicken brain endothelial cells form tight junctions which are positive for claudin-1, claudin-5, occludin and ZO-1. In agreement with the higher P-face association of tight junctions in vivo, chicken brain endothelia exhibited a slightly stronger labeling for claudin-1 at membrane contacts. Brain endothelial cells of both species showed a significant alteration of tight junctions in vitro, indicating a loss of barrier function. Rat endothelial cells showed a characteristic switch of tight junction particles from the P-face to the E-face, accompanied by the loss of claudin-1 in immunofluorescence labeling. In contrast, chicken brain endothelial cells did not show such a switch of particles, although they also lost claudin-1 in culture. These results demonstrate that the maintenance of rat and chicken endothelial barrier function depends on the brain microenvironment. Interestingly, the alteration of tight junctions is different in rat and chicken. This implies that the rat and chicken brain endothelial tight junctions are regulated differently.

Animals↗
PubMed2002

Astrocyte-endothelial interactions and blood-brain barrier permeability.

The blood-brain barrier (BBB) is formed by brain endothelial cells lining the cerebral microvasculature, and is an important mechanism for protecting the brain from fluctuations in plasma composition, and from circulating agents such as neurotransmitters and xenobiotics capable of disturbing neural function. The barrier also plays an important role in the homeostatic regulation of the brain microenvironment necessary for the stable and co-ordinated activity of neurones. The BBB phenotype develops under the influence of associated brain cells, especially astrocytic glia, and consists of more complex tight junctions than in other capillary endothelia, and a number of specific transport and enzyme systems which regulate molecular traffic across the endothelial cells. Transporters characteristic of the BBB phenotype include both uptake mechanisms (e.g. GLUT-1 glucose carrier, L1 amino acid transporter) and efflux transporters (e.g. P-glycoprotein). In addition to a role in long-term barrier induction and maintenance, astrocytes and other cells can release chemical factors that modulate endothelial permeability over a time-scale of seconds to minutes. Cell culture models, both primary and cell lines, have been used to investigate aspects of barrier induction and modulation. Conditioned medium taken from growing glial cells can reproduce some of the inductive effects, evidence for involvement of diffusible factors. However, for some features of endothelial differentiation and induction, the extracellular matrix plays an important role. Several candidate molecules have been identified, capable of mimicking aspects of glial-mediated barrier induction of brain endothelium; these include TGFbeta, GDNF, bFGF, IL-6 and steroids. In addition, factors secreted by brain endothelial cells including leukaemia inhibitory factor (LIF) have been shown to induce astrocytic differentiation. Thus endothelium and astrocytes are involved in two-way induction. Short-term modulation of brain endothelial permeability has been shown for a number of small chemical mediators produced by astrocytes and other nearby cell types. It is clear that endothelial cells are involved in both long- and short-term chemical communication with neighbouring cells, with the perivascular end feet of astrocytes being of particular importance. The role of barrier induction and modulation in normal physiology and in pathology is discussed.

Animals↗
PubMed1985

Tightness of the blood-brain barrier and evidence for brain interstitial fluid flow in the cuttlefish, Sepia officinalis.

Cephalopod molluscs have complex brains and behaviour, yet little is known about the permeability of their blood-brain interface. The accompanying paper characterized the fluid compartments of the brain and presented evidence for restricted permeability of the blood-brain interface to albumin. The present paper investigates the permeability of the interface to small non-electrolytes. [14C]Polyethylene glycol (PEG, mol. wt. 4000), and [51Cr]EDTA (mol. wt. 342) were injected intravenously or intramuscularly, and their penetration into brain and muscle studied up to 48 h. Tracers equilibrated with muscle interstitial fluid (ISF) at relatively short times, but in brain ISF reached only 0.5-0.65 X their plasma concentration. This is qualitative evidence for the presence in brain of a barrier to these molecules and an efficient drainage mechanism for ISF. Quantitative treatment of the uptake data allows calculation of the permeability X surface area product (PS) and the permeability coefficient (P). For the brain PS and P are in the range 1-3 X 10(-4) ml g-1 min-1 and 1-3 X 10(-8) cm s-1 respectively, (PEG), and 3 X 10(-4) ml g-1 min-1 and 3-4 X 10(-8) cm s-1 respectively (Cr-EDTA). The P values are close to those reported for mammalian brain. Assuming that the lack of equilibration in brain is due to ISF flow, the rate of flow can be calculated. Values for vertical and optic lobe are approximately 0.2 microliter g-1 min-1, again close to those reported for mammalian brain. It is concluded that the tightness of the Sepia blood-brain barrier approaches that of mammals, and a flowing ISF system is present. An association between a tight barrier and higher central nervous system integrative function is suggested. The significance of these findings for the evolution of control of the brain microenvironment is discussed.

Animals↗
PubMed2005

Pathobiology of brain metastases.

Brain metastasis is a major cause of systemic cancer morbidity and mortality. Many factors participate in the development and maintenance of brain metastases. The survival of the metastasis depends upon crucial interactions between tumour cells and the brain microenvironment during its development at the new site. This review focuses on the pathobiological mechanisms involved in the establishment and regulation of brain metastases. Developments in molecular biology have vastly expanded our knowledge about the mechanisms of invasion, proliferation, metastatic cell signalling, and angiogenesis in brain metastases. Advances in this understanding of the pathobiology of brain metastasis may lead to novel targeted treatment paradigms and a better prognosis for patients with brain metastatic disease.

Brain Neoplasms↗
PubMed2026

Decoding glioblastoma evolution and heterogeneity through mechanistic modeling: implications for clinical translation.

Glioblastoma (GBM) is one of the most aggressive and lethal primary brain tumors in adults, characterized by dynamic clonal evolution and extensive genomic, cellular, spatial, and microenvironmental heterogeneity. Multi-omics studies have revealed that GBM follows complex evolutionary trajectories involving genetic, epigenetic, transcriptional, and immune-microenvironmental remodeling as tumors grow, adapt to the brain microenvironment, and acquire therapeutic resistance. Increasing evidence suggests that GBM may originate from aberrant neural stem or progenitor cells, including those residing in the subventricular zone, and that glioblastoma stem cells (GSCs) contribute to tumor propagation, heterogeneity, and recurrence. A key conceptual challenge is to reconcile hierarchical cancer stem cell models, in which GSCs are viewed as relatively stable tumor-propagating subpopulations, with dynamic state plasticity models, in which stem-like properties can be reversibly acquired or lost during transitions among proneural-like, mesenchymal-like, invasive, and therapy-tolerant states. Recent advances in single-cell profiling, spatial transcriptomics, lineage tracing, organoid culture, 3D bioprinting, genetically engineered models, and artificial intelligence (AI)-assisted computational modeling have substantially improved the ability to study these processes. However, no currently available model fully recapitulates human GBM heterogeneity, recurrence, treatment history, and tumor-microenvironment interactions. Therefore, model selection should be guided by clearly defined mechanistic questions rather than by reliance on any single platform. This review summarizes current advances in in vitro, ex vivo, in vivo, and computational models for studying GBM evolution and heterogeneity, and discusses how integrated model pipelines may improve preclinical drug testing, treatment-response prediction, and precision neuro-oncology.

Humans↗
PubMed2005

Breast cancer metastasis to the central nervous system.

Clinically symptomatic metastases to the central nervous system (CNS) occur in approximately 10 to 15% of patients with metastatic beast cancer. CNS metastases are traditionally viewed as a late complication of systemic disease, for which few effective treatment options exist. Recently, patients with Her-2-positive breast tumors who were treated with trastuzumab have been reported to develop CNS metastases at higher rates, often while responding favorably to treatment. The blood:brain barrier and the unique brain microenvironment are hypothesized to promote distinct molecular features in CNS metastases that may require tailored therapeutic approaches. New research approaches using cell lines that reliably and preferentially metastasize in vivo to the brain have been reported. Using such model systems, as well as in vitro analogs of blood-brain barrier penetration and tissue-based studies, new molecular leads into this disease are unfolding.

Antibodies, Monoclonal↗
PubMed1999

Blood-brain barrier mechanisms involved in brain calcium and potassium homeostasis.

This study examined the potential roles of the plasma membrane Ca2+-ATPase (PMCA) at the blood-CSF and blood-brain barriers in brain Ca2+ homeostasis and blood-brain barrier Na+/K+-ATPase subunits in brain K+ homeostasis. During dietary-induced hypo- and hypercalcemia (0.59+/-0.06 and 1.58+/-0.12 mM [Ca2+]) there was no significant change in choroid plexus PMCA (Western Blots) compared to normocalcemic rats (plasma [Ca2+]: 1.06+/-0.11 mM). In contrast, PMCA in cerebral microvessels isolated from hypocalcemic rats was 150% greater than that in controls (p<0.001). Comparison of the alpha3 subunit of Na+/K+-ATPase from cerebral microvessels isolated from hypo-, normo- and hyperkalemic rats (2.3+/-0.1, 3.9+/-0.1 and 7. 2+/-0.6 mM [K+]) showed a 75% reduction in the amount of this isoform during hyperkalemia. None of the other Na+/K+-ATPase isoforms varied with plasma [K+]. These results suggest that both PMCA and the alpha3 subunit of Na+/K+-ATPase at the blood-brain barrier play a role in maintaining a constant brain microenvironment during fluctuations in plasma composition.

Animals↗
PubMed2002

The seed and soil hypothesis: vascularisation and brain metastases.

The development of a relevant mouse model for the establishment and growth of brain metastases is essential for study of the biology and therapy of brain metastasis. Injection of human tumour cells into the internal carotid artery of syngeneic or nude mice produces experimental metastases in specific regions of the brain; these are not due to patterns of initial cell arrest, motility, or invasiveness, but rather to the ability of metastatic tumour cells to grow. Whether the progressive growth of brain metastases depends on neovascularisation is not clear. Immunohistochemical and morphometric analyses show that the density of blood vessels within experimental metastases in the brains of nude mice, or within brain metastases derived from human lung cancer, is lower than in the adjacent, tumour-free brain parenchyma. However, blood vessels associated with brain metastases are dilated and contain many dividing endothelial cells. Immunohistochemical analysis also reveals that tumour cells located less than 100 microm from a blood vessel are viable, whereas more distant tumour cells undergo apoptosis. The blood-brain barrier is intact in and around experimental brain metastases smaller than 0.25 mm in diameter, but is leaky in larger metastases. Nevertheless, the lesions are resistant to chemotherapeutic drugs. The way in which the brain microenvironment influences the biological behaviour of tumour cells is a subject of intense investigation.

Animals↗
PubMed2001

Differentiation of transplanted bone marrow cells in the adult mouse brain.

BACKGROUND: Bone marrow transplantation is reportedly effective in preventing the progression of neurological deterioration in lysosomal storage disorders, although the mechanism underlying the therapeutic effects remains to be elucidated. Recent research on stem cell biology suggests that bone marrow cells contain nonhematopoietic stem cells, including brain precursor cells. To evaluate the contribution of bone marrow cells as carriers for cell and gene therapy of neurological disorders, we studied the fate of transplanted bone marrow cells in the adult mouse brain. METHODS: Bone marrow cells were genetically marked with a retroviral vector containing the green fluorescence protein gene and then transplanted into irradiated mice by either systemic infusion or direct injection. To identify cell types, brain sections were stained with specific antibodies against neuronal cell markers-neuron specific enolase for neurons, glial fibrillary acidic protein (GFAP) for astrocytes, carbonic anhydrase II (CAII) for oligodendrocytes, and ionized calcium binding adaptor molecule 1 (Iba1) for microglia-and then examined under a confocal microscope. RESULTS: Twenty-four weeks after systemic infusion, transplanted cells expressed Iba1 but none of the other brain cell markers. Conversely, 12 weeks after direct injection, transplanted cells were stained with antibodies against GFAP, CAII, and Iba1. CONCLUSIONS: Bone marrow contains cells capable of differentiating into oligodendrocytes, astrocytes, and microglia when exposed to the brain microenvironment. Autologous bone marrow cells may be useful as carriers for ex vivo gene therapy for lysosomal disorders with neurological symptoms.

Animals↗