scholarly journals Autologous hybrid cell fusion vaccine in a spontaneous intermediate model of breast carcinoma

2019 ◽  
Vol 20 (5) ◽  
Author(s):  
R. Curtis Bird ◽  
Patricia DeInnocentes ◽  
Allison E. Church Bird ◽  
Farruk M. Lutful Kabir ◽  
E. Gisela Martinez-Romero ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Cell Fusion ◽  
Hybrid Cell ◽  
Intermediate Model

scholarly journals Human CardioChimeras: Creation of a Novel ‘Next Generation’ Cardiac Cell

2019 ◽  
Author(s):  
Fareheh Firouzi ◽  
Sarmistha Sinha Choudhury ◽  
Kathleen Broughton ◽  
Adriana Salazar ◽  
Mark A Sussman
Keyword(s):  
Cell Fusion ◽  
Human Heart ◽  
Sendai Virus ◽  
Hybrid Cell ◽  
Cell Types ◽  
Heart Tissue ◽  
List Type ◽  
Hybrid Cells ◽  
Next Generation ◽  
Human Heart Tissue

AbstractBackgroundCardioChimeras (CCs) produced by fusion of murine c-kit+ cardiac interstitial cells (cCIC) with mesenchymal stem cells (MSCs) promote superior structural and functional recovery in a mouse model of myocardial infarction (MI) compared to either precursor cell alone or in combination. Creation of human CardioChimeras (hCC) represents the next step in translational development of this novel cell type, but new challenges arise when working with cCICs isolated and expanded from human heart tissue samples. The objective of the study was to establish a reliable cell fusion protocol for consistent optimized creation of hCCs and characterize fundamental hCC properties.Methods and ResultsCell fusion was induced by incubating human cCICs and MSCs at a 2:1 ratio with inactivated Sendai virus. Hybrid cells were sorted into 96-well microplates for clonal expansion to derive unique cloned hCCs, which were then characterized for various cellular and molecular properties. hCCs exhibited enhanced survival relative to the parent cells and promoted cardiomyocyte survival in response to serum deprivation in vitro.ConclusionsThe generation of hCC is demonstrated and validated in this study, representing the next step toward implementation of a novel cell product for therapeutic development. Feasibility of creating human hybrid cells prompts consideration of multiple possibilities to create novel chimeric cells derived from cells with desirable traits to promote healing in pathologically damaged myocardium.Clinical Perspective“Next generation” cell therapeutics will build upon initial findings that demonstrate enhanced reparative action of combining distinct cell types for treatment of cardiomyopathic injury.Differential biological properties of various cell types are challenging for optimization of delivery, engraftment, persistence, and synergistic action when used in combination.Creation of a novel hybrid cell called a CardioChimera overcomes limitations inherent to use of multiple cell types.CardioChimeras exhibit unique properties relative to either parental cell anticipated to be advantageous in cellular therapeutic applications.CardioChimeras have now been created and characterized using cells derived from human heart tissue, advancing initial proof of concept previously demonstrated with mice.CardioChimeras represent an engineered solution that can be implemented as a path forward for improving the outcome of myocardial cell therapy.

scholarly journals Hybrid Formation and Fusion of Cancer Cells In Vitro and In Vivo

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4496
Author(s):  
Ralf Hass ◽  
Juliane von der Ohe ◽  
Thomas Dittmar
Keyword(s):  
Cell Fusion ◽  
Cancer Cell ◽  
Selection Process ◽  
Hybrid Cell ◽  
Chromosomal Rearrangements ◽  
Immune Surveillance ◽  
Hybrid Cells ◽  
Tumor Plasticity

The generation of cancer hybrid cells by intra-tumoral cell fusion opens new avenues for tumor plasticity to develop cancer stem cells with altered properties, to escape from immune surveillance, to change metastatic behavior, and to broaden drug responsiveness/resistance. Genomic instability and chromosomal rearrangements in bi- or multinucleated aneuploid cancer hybrid cells contribute to these new functions. However, the significance of cell fusion in tumorigenesis is controversial with respect to the low frequency of cancer cell fusion events and a clonal advantage of surviving cancer hybrid cells following a post-hybrid selection process. This review highlights alternative processes of cancer hybrid cell development such as entosis, emperipolesis, cannibalism, therapy-induced polyploidization/endoreduplication, horizontal or lateral gene transfer, and focusses on the predominant mechanisms of cell fusion. Based upon new properties of cancer hybrid cells the arising clinical consequences of the subsequent tumor heterogeneity after cancer cell fusion represent a major therapeutic challenge.

scholarly journals Altered Tumor Plasticity after Different Cancer Cell Fusions with MSC

2020 ◽  
Vol 21 (21) ◽  
pp. 8347 ◽  
Author(s):  
Catharina Melzer ◽  
Juliane von der Ohe ◽  
Ralf Hass
Keyword(s):  
Cancer Cells ◽  
Cell Fusion ◽  
Cancer Cell ◽  
Human Cancer ◽  
Selection Process ◽  
Hybrid Cell ◽  
Therapeutic Interventions ◽  
Cellular Interactions ◽  
Tumor Plasticity

While cell fusion demonstrates an important pathway during tissue development and regeneration of distinct organs, this process can also contribute to pathophysiological phenotypes during tumor progression. Hybrid cell formation after heterofusion between cancer cells and various other cell types within the tumor microenvironment is observed in vitro and in vivo. In particular, mesenchymal stroma/stem-like cells (MSC) perform diverse levels of communication with cancer cells by exhibiting anti- and pro-tumorigenic effects. During these cellular interactions, MSC can eventually fuse with cancer cells. Thereby, the newly generated disparate hybrid populations display aneuploidy associated with chromosomal instability. Based upon a subsequent post-hybrid selection process (PHSP), fused cancer cells can undergo apoptosis/necroptosis, senescence, dormancy, or a proliferative state by acquisition of new properties. Consequently, PHSP-surviving hybrid cancer cells demonstrate altered functionalities within the tumor tissue. This is accompanied by changes in therapeutic responsiveness and a different metastatic behavior. Accordingly, enhanced tumor plasticity interferes with successful therapeutic interventions and aggravates patient prognoses. The present review article focusses on fusion of MSC with different human cancer cells, in particular breast cancer populations and resulting characteristics of various cancer hybrid cells. Moreover, some mechanisms of cancer cell fusion are discussed together with multiple PHSP pathways.

Epstein-Barr Virus Lytic Cycle Spreads Via Cell Fusion in a Nasopharyngeal Carcinoma Hybrid Cell Line

1994 ◽  
Vol 104 (1) ◽  
pp. 91???94 ◽  
Author(s):  
Tomokazu Yoshizaki ◽  
Toru Takimoto ◽  
Hazime Takeshita ◽  
Saichiro Tanaka ◽  
Mitsuru Furukawa ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cell Line ◽  
Cell Fusion ◽  
Epstein Barr Virus ◽  
Hybrid Cell ◽  
Lytic Cycle ◽  
Hybrid Cell Line ◽  
Barr Virus ◽  
Epstein Barr

An allogeneic hybrid-cell fusion vaccine against canine mammary cancer

2008 ◽  
Vol 123 (3-4) ◽  
pp. 289-304 ◽  
Author(s):  
R. Curtis Bird ◽  
Patricia DeInnocentes ◽  
Steven Lenz ◽  
Erin E. Thacker ◽  
David T. Curiel ◽  
...  
Keyword(s):  
Cell Fusion ◽  
Mammary Cancer ◽  
Hybrid Cell ◽  
Canine Mammary Cancer

scholarly journals Involvement of Actin Cytoskeletal Components in Breast Cancer Cell Fusion with Human Mesenchymal Stroma/Stem-Like Cells

2019 ◽  
Vol 20 (4) ◽  
pp. 876 ◽  
Author(s):  
Catharina Melzer ◽  
Juliane von der Ohe ◽  
Ralf Hass
Keyword(s):  
Breast Cancer ◽  
Cell Fusion ◽  
Molecular Mechanisms ◽  
Hybrid Cell ◽  
Cell Formation ◽  
Rare Event ◽  
Cytochalasin D ◽  
Cytoskeletal Proteins ◽  
Hybrid Cells ◽  
Mesenchymal Stroma

Cell fusion as a rare event was observed following the co-culture of human MDA-MB-231cherry breast cancer cells or benign neoplastic MCF10Acherry breast epithelial cells together with different mesenchymal stroma/stem-like cells (MSCGFP) cultures, respectively, resulting in the generation of double-fluorescing hybrid cells. Analysis of potential molecular mechanisms for the formation of cancer hybrid cells revealed cytoskeletal components, including F-actin. Thus, a sub-lethal concentration of cytochalasin D, which blocks elongation of actin filaments, was able to significantly reduce cancer hybrid cell formation. Simultaneously, cell cycle progression of the different co-cultures remained unaffected following treatment with cytochalasin D, indicating continued proliferation. Moreover, exposure to 50 nM cytochalasin D revealed little if any effect on the expression of various integrins and cell adhesion molecules in the different co-cultures. However, LC-MS proteome analysis of the different control co-cultures compared to corresponding cytochalasin-treated co-cultures demonstrated predominant differences in the expression of actin-associated cytoskeletal proteins. In addition, the requirement of structured actin to provide an appropriate cytoskeletal network for enabling subsequent fusion processes was also substantiated by the actin filament disrupting latrunculin B, which inhibits the fusion process between the breast cancer populations and mesenchymal stroma/stem-like cells (MSC). Together, these findings suggest an important role of distinct actin structures and associated cytoskeletal components during cell fusion and the formation of breast cancer hybrid cells.

An autologous dendritic cell canine mammary tumor hybrid-cell fusion vaccine

2010 ◽  
Vol 60 (1) ◽  
pp. 87-97 ◽  
Author(s):  
R. Curtis Bird ◽  
Patricia DeInnocentes ◽  
Allison E. Church Bird ◽  
Frederik W. van Ginkel ◽  
Joni Lindquist ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Cell Fusion ◽  
Mammary Tumor ◽  
Hybrid Cell ◽  
Canine Mammary Tumor ◽  
Autologous Dendritic Cell

Mouse oocytes and parthenogenetic eggs lose the ability to be penetrated by spermatozoa after fusion with zygotes

Zygote ◽  
1998 ◽  
Vol 6 (4) ◽  
pp. 321-328 ◽  
Author(s):  
Anna Krukowska ◽  
Ewa Wielkopolska ◽  
Renata Czolłwska ◽  
M. Maleszewski ◽  
A.K. Tarkowski
Keyword(s):  
Cell Fusion ◽  
Hybrid Cell ◽  
Hybrid Cells ◽  
Mouse Oocytes ◽  
Sperm Penetration ◽  
Mouse Eggs

Fertilised mouse eggs develop the oolemma block to sperm penetration within 1 h. This block makes zona-free eggs at the pronuclear stage (zygotes) fully resistant to sperm penetration. In this study we investigated whether this block can spread – as a result of cell fusion – to the oolemma of eggs that are competent to be penetrated by spermatozoa. Preovulatory (GV) oocytes, ovulated oocytes in metaphase II (MII) and 1-cell parthenotes were fused with zygotes and the hybrid cells inseminated at various intervals after fusion. Sperm penetration was assessed on the basis of the presence of Giemsa-positive sperm heads in the air-dried preparations. The oolemma block to sperm penetration develops in all types of hybrids although at different speeds: it develops fast (2–3 h) in oolemma derived from MII oocytes and artificially activated eggs, and slowly in oolemma derived from GV oocytes. In the GV oocyte–zygote hybrids the time of formation of the block varied: while 50% of cells lost the ability to fuse with sperm by 2 h after fusion, in the remaining cells the block must have developed some time between 5 and 18 h after fusion. How these sperm-induced modifications of the oolemma of fertilised egg spread in the hybrid cell and render the ‘virgin’ part of oolemma resistant to sperm penetration remains unknown.

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