Features and distribution of intracerebrally injected peritoneal macrophages

Oehmichen, M.; Wiethölter, H.; Grüninger, H; Genčić, M.

doi:10.1016/s0014-4908(79)80029-0

Cited by 5 publications

(4 citation statements)

References 13 publications

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“…In agreement with previous reports, our results show that Mo/MØ have a significant potential for their integration in the CNS [14][15][16] and can ensure long lasting transgene expression [13] without inducing a particular inflammatory response [13][14][15][16]. Our data further show that Mo and MØ behave similarly and express the same levels of transgene after in vivo transplantation.…”

Section: Resultssupporting

confidence: 92%

“…So far, MØ have been administered intravenously as therapeutic effectors in several models of diseases such as cancer [8], muscular damage [9], neuro AIDS [10] or lysosomal enzyme deficiencies [11,12]. In the CNS, grafts of MØ have been performed either to survey their fate and survival [13][14][15] or to evaluate a therapeutic contribution in spinal cord or brain models of injury [16,17] or neurodegenerative processes like Parkinson disease [18].…”

Section: Introductionmentioning

confidence: 99%

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Long term survival and limited migration of genetically modified monocytes/macrophages grafted into the mouse brain

Sarkis¹,

Gras²,

Sanchez³

et al. 2013

JBiSE

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In mammals, myeloid progenitors infiltrate the developing central nervous system (CNS), through the immature blood-brain barrier (BBB), the ventricular layer or the pial surface migrate and give rise to resident microglia. In the mature brain, however, the BBB hampers such recruitment from the blood-stream and long-term establishment of blood borne myeloid cells in the CNS thus appears at best limited. Hematopoietic stem cell-derived microglia, nevertheless, represents a promising tool for the correction of genetic deficits in the brain. We thus investigated the fate of primary human monocytes, and monocyte-derived macrophages, following transplantation into the adult mouse brain overpassing the BBB. Furthermore, we documented the ability of such cells to deliver a lysosomal enzyme into the brain following genetic modification with a recombinant adenoviral vector carrying the human β-glucuronidase cDNA. When implanted into the mouse striatum, the engineered primary cells survived and expressed the transgene for as much as 8 months. Moreover, the donor cells could migrate out of the grafting site and settle along blood vessels or myelin tracts although at limited distance. Migrating donor cells down-regulated the expression of CD14 andHLA DR, suggesting the adoption of a deactivated microglia-like phenotype. Our observations establish the ability of circulating mononuclear phagocytes to integrate into the brain after transplantation and express a transgene on the long term. These cells might thus be employed for autologous transplantation for the delivery of secreted therapeutic proteins in the context of a wide range of brain affections.

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Section: Resultssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Long term survival and limited migration of genetically modified monocytes/macrophages grafted into the mouse brain

Sarkis¹,

Gras²,

Sanchez³

et al. 2013

JBiSE

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“…His conviction of the mesodermal origin of microglia was supported both by studies coupling light/electron microscopy and immunohistochemistry, which recognized typical morphological features of macrophages in the various stages of microglial development (Murabe and Sano, 1982), and by the demonstration that microglial cells reacted positively to antisera recognizing monocyte/macrophage antigens (Hume et al, 1983; Murabe and Sano, 1983). Despite the emerging evidence of the relationship of microglia to macrophages, other reports led to variable interpretations due to a lack of homology between monocytes and mature microglia in the expression of certain antigens, complicating the issue (Oehmichen et al, 1979; Wood et al, 1979). Nevertheless, the data showing phenotypic homologies between monocytes/macrophages and microglia were eventually validated by immunohistochemical studies that reported the specific expression of macrophage markers, including F4/80, Fc receptor and CD11b in mouse microglia (Perry et al, 1985), as well as FcGRI, and CD11b in their human counterparts (Akiyama and McGeer, 1990).…”

Section: Historical Perspectives On the Nature Of Microgliamentioning

confidence: 99%

Origin and differentiation of microglia

Ginhoux¹,

Lim²,

Hoeffel³

et al. 2013

Front. Cell. Neurosci.

707

557

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Microglia are the resident macrophage population of the central nervous system (CNS). Adequate microglial function is crucial for a healthy CNS. Microglia are not only the first immune sentinels of infection, contributing to both innate and adaptive immune responses locally, but are also involved in the maintenance of brain homeostasis. Emerging data are showing new and fundamental roles for microglia in the control of neuronal proliferation and differentiation, as well as in the formation of synaptic connections. While microglia have been studied for decades, a long history of experimental misinterpretation meant that their true origins remained debated. However, recent studies on microglial origin indicate that these cells in fact arise early during development from progenitors in the embryonic yolk sac (YS) that seed the brain rudiment and, remarkably, appear to persist there into adulthood. Here, we review the history of microglial cells and discuss the latest advances in our understanding of their origin, differentiation, and homeostasis, which provides new insights into their roles in health and disease.

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“…However, there is some evidence that a relapse may be initiated peripherally, for recent studies on lymphocyte migration have found CD2-positive cells crossing the blood-brain barrier from the blood into the CSF in progressive MS (Hafler & Weiner, 1987). It has also been suggested that cells may circulate from the CNS to the blood (Oehmichen et al, 1979;Wekerle et al, 1986). Therefore, the Correspondence: Samantha J. Owen, Department of Neurochemistry, Institute of Neurology, London WCIN 3BG, UK.…”

Section: Introductionmentioning

confidence: 99%

Degradation of human myelin in vitro by leucocytes from patients with multiple sclerosis

Owen¹,

Watson²,

Davison³

1990

Clinical and Experimental Immunology

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SUMMARYIn order to study the possible autoimmune basis of multiple sclerosis (MS) a quantitative method has been used to investigate breakdown of human myelin in vitro. We found that serum from MS patients and controls was generally devoid of any myelin degradative activity. However, isolated peripheral blood mononuclear cells from 43% of MS patients showed significant myelin degradative activity as did those from 61-5% of patients with rheumatoid arthritis (RA). Myelin degradation by cells was found in only 13% of patients with other neurological diseases and in no healthy controls. It is proposed that this non-specific peripheral cellular immune degradative activity originates from cells activated within the central nervous system of MS patients or the joints of individuals with RA. As a result, activity in the blood only indirectly reflects the ongoing inflammatory response at the primary site, accounting for the lack of correlation between changes in the blood and the clinical status of the MS patient. We further propose that the lack of m vitro myelin degradative activity in cells recovered from the cerebrospinal fluid is due to autoaggressive cells being sequestered to the brain.

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Features and distribution of intracerebrally injected peritoneal macrophages

Cited by 5 publications

References 13 publications

Long term survival and limited migration of genetically modified monocytes/macrophages grafted into the mouse brain

Long term survival and limited migration of genetically modified monocytes/macrophages grafted into the mouse brain

Origin and differentiation of microglia

Degradation of human myelin in vitro by leucocytes from patients with multiple sclerosis

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