4 Placental Hofbauer Cells As a Proxy Cell Type for Fetal Brain Microglia

Context.—The placenta is an important component in understanding the fetal response to intrauterine Zika virus infection, but the pathologic changes in this organ remain largely unknown. Hofbauer cells are fetal-derived macrophages normally present in the chorionic villous stroma. They have been implicated in a variety of physiological and pathologic processes, in particular involving infectious agents. Objectives.—To characterize the fetal and maternal responses and viral localization in the placenta following Zika virus transmission to an 11 weeks' gestation fetus. The clinical course was notable for prolonged viremia in the mother and extensive neuronal necrosis in the fetus. The fetus was delivered at 21 weeks' gestation after pregnancy termination. Design.—The placenta was evaluated by using immunohistochemistry for inflammatory cells (macrophages/monocytes [Hofbauer cells], B and T lymphocytes) and proliferating cells, and an RNA probe to Zika virus. The fetal brain and the placenta were previously found to be positive for Zika virus RNA by reverse transcription–polymerase chain reaction. Results.—The placenta demonstrated prominently enlarged, hydropic chorionic villi with hyperplasia and focal proliferation of Hofbauer cells. The degree of Hofbauer cell hyperplasia gave an exaggerated immature appearance to the villi. No acute or chronic villitis, villous necrosis, remote necroinflammatory abnormalities, chorioamnionitis, funisitis, or hemorrhages were present. An RNA probe to Zika virus was positive in villous stromal cells, presumably Hofbauer cells. Conclusions.—Zika virus placental infection induces proliferation and prominent hyperplasia of Hofbauer cells in the chorionic villi but does not elicit villous necrosis or a maternal or fetal lymphoplasmacellular or acute inflammatory cell reaction.

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Post-Thaw Viability and Functionality of Cryopreserved Rat Fetal Brain Cells Cocultured with Sertoli Cells

Cell Transplantation ◽

10.1177/096368979700600212 ◽

1997 ◽

Vol 6 (2) ◽

pp. 185-189 ◽

Cited By ~ 15

Author(s):

D.F. Cameron ◽

A.I. Othberg ◽

C.V. Borlongan ◽

S. Rashed ◽

A. Anton ◽

...

Keyword(s):

Sertoli Cells ◽

Trypan Blue ◽

Fetal Brain ◽

Trophic Factors ◽

Cell Type ◽

Isolated Cells ◽

Trypan Blue Exclusion ◽

Ventral Mesencephalic ◽

Privileged Site

Testis-derived Sertoli cells have been used to create an immune “privileged” site outside of the testis to facilitate cell transplantation protocols for diabetes and neurodegenerative diseases. In addition to secreting immunoprotective factors, Sertoli cells also secrete growth and trophic factors that appear to enhance the posttransplantation viability of isolated cells and, likewise, the postthaw viability of isolated, cryopreserved cells (26). It would be beneficial if Sertoli cells could be cryopreserved with the transplantable cell type without deleterious effects on the cells. This report describes a protocol for the cocryopreservation of rat Sertoli cells with rat ventral mesencephalic neurons, neurons from the lateral and medial ganglionic eminences and the hNT neuron cell line, and reports on the effects of Sertoli cells on the the postthaw viability of these neurons. Results of trypan blue exclusion analysis indicated that the presence of Sertoli cells did not deleteriously effect cryopreserved neurons and may improve their postthaw recoverability and viability in general. Specifically, results of the tyrosine hydroxylase immunostaining showed that Sertoli cells significantly enhance the postthaw viability of ventral mesencephalic dopaminergic cells in vitro.

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Single cell profiling of Hofbauer cells and fetal brain microglia reveals shared programs and functions

10.1101/2021.12.03.471177 ◽

2021 ◽

Author(s):

Alexis M Ceasrine ◽

Rebecca Batorsky ◽

Lydia L. Shook ◽

Sezen Kislal ◽

Evan A. Bordt ◽

...

Keyword(s):

Single Cell ◽

Fetal Brain ◽

Lineage Tracing ◽

Rna Seq ◽

Neurodevelopmental Outcomes ◽

Female Fetus ◽

Hofbauer Cells ◽

Single Cell Profiling ◽

Placental Macrophages ◽

Noninvasive Biomarkers

SummaryMaternal immune activation is associated with adverse offspring neurodevelopmental outcomes, many of which are mediated by in utero microglial programming. Microglia remain inaccessible at birth and throughout development, thus identification of noninvasive biomarkers that can reflect fetal brain microglial programming may permit screening and intervention during critical developmental windows. Here we used lineage tracing to demonstrate the shared ontogeny between fetal brain macrophages (microglia) and fetal placental macrophages (Hofbauer cells). Single-cell RNA sequencing of murine fetal brain and placental macrophages demonstrated shared transcriptional programs. Comparison with human datasets demonstrated that placental resident macrophage signatures are highly conserved between mice and humans. Single-cell RNA-seq identified sex differences in fetal microglial and Hofbauer cell programs, and robust differences between placenta-associated maternal macrophage/monocyte (PAMM) populations in the context of a male versus a female fetus. We propose that Hofbauer cells, which are easily accessible at birth, provide novel insights into fetal brain microglial programs, potentially facilitating the early identification of offspring most vulnerable to neurodevelopmental disorders.

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Molecular Pathology Demonstration of SARS-CoV-2 in Cytotrophoblast from Placental Tissue with Chronic Histiocytic Intervillositis, Trophoblast Necrosis and COVID-19

Journal of Developmental Biology ◽

10.3390/jdb9030033 ◽

2021 ◽

Vol 9 (3) ◽

pp. 33

Author(s):

David A. Schwartz ◽

Mattia Bugatti ◽

Amerigo Santoro ◽

Fabio Facchetti

Keyword(s):

Molecular Pathology ◽

Placental Tissue ◽

Physical Contact ◽

Positive Staining ◽

Fibrin Deposition ◽

Cell Type ◽

Hofbauer Cells ◽

Capillary Endothelial Cells ◽

Rna In Situ Hybridization ◽

Cytotrophoblast Cells

A subset of placentas from pregnant women having the SARS-CoV-2 infection have been found to be infected with the coronavirus using molecular pathology methods including immunohistochemistry and RNA in situ hybridization. These infected placentas can demonstrate several unusual findings which occur together—chronic histiocytic intervillositis, trophoblast necrosis and positive staining of the syncytiotrophoblast for SARS-CoV-2. They frequently also have increased fibrin deposition, which can be massive in some cases. Syncytiotrophoblast is the most frequent fetal-derived cell type to be positive for SARS-CoV-2. It has recently been shown that in a small number of infected placentas, villous stromal macrophages, termed Hofbauer cells, and villous capillary endothelial cells can also stain positive for SARS-CoV-2. This report describes a placenta from a pregnant woman with SARS-CoV-2 that had chronic histiocytic intervillositis, trophoblast necrosis, increased fibrin deposition and positive staining of the syncytiotrophoblast for SARS-CoV-2. In addition, molecular pathology testing including RNAscope and immunohistochemistry for SARS-CoV-2 and double-staining immunohistochemistry using antibodies to E-cadherin and GATA3 revealed that cytotrophoblast cells stained intensely for SARS-CoV-2. All of the cytotrophoblast cells that demonstrated positive staining for SARS-CoV-2 were in direct physical contact with overlying syncytiotrophoblast that also stained positive for the virus. The pattern of cytotrophoblast staining for SARS-CoV-2 was patchy, and there were chorionic villi having diffuse positive staining of the syncytiotrophoblast for SARS-CoV-2, but without staining of cytotrophoblast. This first detailed description of cytotrophoblast involvement by SARS-CoV-2 adds another fetal cell type from infected placentas that demonstrate viral staining.

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Single Cell Profiling of Hofbauer Cells and Fetal Brain Microglia Reveals Shared Programs and Functions

SSRN Electronic Journal ◽

10.2139/ssrn.3985607 ◽

2021 ◽

Author(s):

Alexis Caesarine ◽

Rebecca Batorsky ◽

Lydia Shook ◽

Sezen Kislal ◽

Evan Bordt ◽

...

Keyword(s):

Single Cell ◽

Fetal Brain ◽

Hofbauer Cells ◽

Single Cell Profiling

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Ultrastructural Correlations between Clonal Human Tumor Colonies and in Vivo Neoplasms

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100053711 ◽

1982 ◽

Vol 40 ◽

pp. 210-211

Author(s):

M.J. Murphy ◽

R.R. Price ◽

J.C. Sloman

Keyword(s):

Cultured Cells ◽

Human Tumor ◽

Cell Type ◽

Tumor Mass ◽

Initial Cell ◽

Cloning Assay ◽

Human Tumor Cloning ◽

The Relationship

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.

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Some Observations on Changes in Denervated Taste Buds of Circumvallate Papillae of Rabbits

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100063457 ◽

1969 ◽

Vol 27 ◽

pp. 308-309

Author(s):

Sunao Fujimoto ◽

Raymond G. Murray ◽

Assia Murray

Keyword(s):

Taste Buds ◽

Taste Bud ◽

Cell Type ◽

Dark Cells ◽

Type Iii ◽

Circumvallate Papillae ◽

Taste Bud Cells ◽

Light Cells

Taste bud cells in circumvallate papillae of rabbit have been classified into three groups: dark cells; light cells; and type III cells. Unilateral section of the 9th nerve distal to the petrosal ganglion was performed in 18 animals, and changes of each cell type in the denervated buds were observed from 6 hours to 10 days after the operation.Degeneration of nerves is evident at 12 hours (Fig. 1) and by 2 days, nerves are completely lacking in the buds. Invasion by leucocytes into the buds is remarkable from 6 to 12 hours but then decreases. Their extrusion through the pore is seen. Shrinkage and disturbance in arrangement of cells in the buds can be seen at 2 days. Degenerated buds consisting of a few irregular cells and remnants of degenerated cells are present at 4 days, but buds apparently normal except for the loss of nerve elements are still present at 6 days.

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Dendritic cells of the human epidermis: immuno-electron microscopic studies of la antigen reactivity

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100084090 ◽

1978 ◽

Vol 36 (2) ◽

pp. 644-645

Author(s):

G. Rowden ◽

M. G. Lewis ◽

T. M. Phillips

Keyword(s):

Dendritic Cells ◽

Langerhans Cells ◽

Cell Types ◽

Cell Type ◽

Electron Microscopic ◽

La Antigen ◽

Microscopic Studies ◽

A Cell ◽

C3 Receptors ◽

Antigen Reactivity

Langerhans cells of mammalian stratified squamous epithelial have proven to be an enigma since their discovery in 1868. These dendritic suprabasal cells have been considered as related to melanocytes either as effete cells, or as post divisional products. Although grafting experiments seemed to demonstrate the independence of the cell types, much confusion still exists. The presence in the epidermis of a cell type with morphological features seemingly shared by melanocytes and Langerhans cells has been especially troublesome. This so called "indeterminate", or " -dendritic cell" lacks both Langerhans cells granules and melanosomes, yet it is clearly not a keratinocyte. Suggestions have been made that it is related to either Langerhans cells or melanocyte. Recent studies have unequivocally demonstrated that Langerhans cells are independent cells with immune function. They display Fc and C3 receptors on their surface as well as la (immune region associated) antigens.

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Lymphoproliferative disorders (LPD) involving lungs: T and B cell subsets within pulmonary infiltrates and in peripheral blood

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010011338x ◽

1984 ◽

Vol 42 ◽

pp. 700-701

Author(s):

Irene Stachura ◽

Milton H. Dalbow ◽

Michael J. Niemiec ◽

Matias Pardo ◽

Gurmukh Singh ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Lymphoproliferative Disorders ◽

Mixed Population ◽

Lymphoid Cells ◽

Lymphomatoid Granulomatosis ◽

Cell Type ◽

Cell Surface Antigens ◽

Pulmonary Infiltrates ◽

B Cell Subsets

Lymphoid cells were analyzed within pulmonary infiltrates of six patients with lymphoproliferative disorders involving lungs by immunofluorescence and immunoperoxidase techniques utilizing monoclonal antibodies to cell surface antigens T11 (total T), T4 (inducer/helper T), T8 (cytotoxic/suppressor T) and B1 (B cells) and the antisera against heavy (G,A,M) and light (kappa, lambda) immunoglobulin chains. Three patients had pseudolymphoma, two patients had lymphoma and one patient had lymphomatoid granulomatosis.A mixed population of cells was present in tissue infiltrates from the three patients with pseudolymphoma, IgM-kappa producing cells constituted the main B cell type in one patient. In two patients with lymphoma pattern the infiltrates were composed exclusively of T4+ cells and IgG-lambda B cells predominated slightly in the patient with lymphomatoid granulomatosis.

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Nuclear receptors in disease: the oestrogen receptors

Essays in Biochemistry ◽

10.1042/bse0400157 ◽

2004 ◽

Vol 40 ◽

pp. 157-167 ◽

Cited By ~ 18

Author(s):

Maria Nilsson ◽

Karin Dahlman-Wright ◽

Jan-Åke Gustafsson

Keyword(s):

Nuclear Receptors ◽

Target Genes ◽

Receptor Subtype ◽

Target Tissue ◽

Oestrogen Receptors ◽

Nucleotide Polymorphisms ◽

Cell Type ◽

Single Nucleotide ◽

Beneficial Effects ◽

The Family

For several decades, it has been known that oestrogens are essential for human health. The discovery that there are two oestrogen receptors (ERs), ERalpha and ERbeta, has facilitated our understanding of how the hormone exerts its physiological effects. The ERs belong to the family of ligand-activated nuclear receptors, which act by modulating the expression of target genes. Studies of ER-knockout (ERKO) mice have been instrumental in defining the relevance of a given receptor subtype in a certain tissue. Phenotypes displayed by ERKO mice suggest diseases in which dysfunctional ERs might be involved in aetiology and pathology. Association between single-nucleotide polymorphisms (SNPs) in ER genes and disease have been demonstrated in several cases. Selective ER modulators (SERMs), which are selective with regard to their effects in a certain cell type, already exist. Since oestrogen has effects in many tissues, the goal with a SERM is to provide beneficial effects in one target tissue while avoiding side effects in others. Refined SERMs will, in the future, provide improved therapeutic strategies for existing and novel indications.

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