Photo Gallery
Blastocyst
A photographic image of a sheep seven- day-old embryo called a blastocyst. At the blastocyst stage, the embryo contains two distinctive cell types, the inner cell mass and trophectoderm which develops into placenta. The nucleus of the inner cell mass cells is stained in blue and the trophectoderm cell nuclei counter-stained in a pink. The different stains are fluorescent and are visualised when exposed to a UV light. A cell nucleus contains the DNA or genetic information, which instructs cell function. (Image taken by Billie Murray, CSIRO Livestock Industries)
Blastocyst two
A bright-field photographic image of a sheep seven-day-old embryo called a blastocyst. The inner part of the blastocyst is a fluid filled cavity. The inner cell mass cells are resident at one polar end and the trophectoderm cells line the cavity. An outer membrane, the zona pellucida, surrounds the preimplantation stage embryo. (Image taken by Billie Murray, CSIRO Livestock Industries)
Mouse liver stem cells
Mouse liver stem cells, visualised using green fluorescent protein or GFP, which expression is associated with a liver stem cell gene. (Image from George Yeoh, University of Western Australia)
TRA160 Human embryonic stem cells
Human mesenchymal stem cells labelled with a dye called phalloidin which stains a cytoskeletal protein, actin. The nuclei are counter-stained. The cell cytoskeleton is the cells scaffolding, structuring the cell and in some cells, providing movement or shuttling of different proteins. (Image taken by Tony Rossetti)
GCTM2 human embryonic stem cell colony
A human embryonic stem cell colony labelled with fluorescence associated with a specific cell surface protein, recognised by an antibody, which recognises GCTM2. The nuclei are stained with a red fluorescent dye. The antibody to GCTM2 recognises the same protein as TRA160. (Image from Stem Cell Sciences, Australia)
About these scientific images
This Image Gallery displays images taken and contributed by ASSCR members and colleagues. The images are of predominately microscopic cells or embryos, not otherwise visible. Often, the images show cells marked with various colours, mostly fluorescent. This method uses antibodies to mark the cells with colours. Though we now use antibodies as tools in the laboratory, the main function of antibodies is to protect us from infection. Though we now know quite a lot about antibodies, this was not always true. Hybridoma technology provides a method to produce antibodies in culture. Nowadays, these assays are the basis of widely used methods using antibodies to identify various proteins and carbohydrates or sugars, providing an essential tool-kit for scientists. In this Image Gallery, most of the fluorescent colours seen in these microscopic images are associated with monoclonal antibodies raised specifically against various proteins, using hybridoma technology. They are then tagged to molecules, such as fluorescent proteins, that can be readily visualised and photographed to provide the necessary evidence. Researchers also use fluorescent dyes that passively incorporate into specific cellular compartments, such as the nucleus.
If you would like to have your stem cell image in our Image Gallery, please email info(at)asscr.org
How the Method Developed - Making Monoclonal Antibodies in Culture
The discovery of hybridoma technology, provided a way to make specific antibodies or monoclonal antibodies, was the result of a number of different research areas over a many years. In 1923, Michael Heidelberger and his mentor Oswald Avery found that protein and carbohydrate antigens elicit antibodies, which were proteins. This critical discovery facilitated subsequent research into the structure of antibodies and how they are made. Research into the genetics and behaviour of cancer cells by fusing one cell to another, unrelated cell and thus forming a cellular hybrid honed methods to be able to successfully fuse cells together. This was imperative for the later development of hybridoma technology involving the fusing an immune cell, known as a B lymphocyte that usually produces specific antibodies to an immortalised myeloma cell line. At the time, this work was important as it developed better ways for researchers to study our immune system, in particular the specificity of an immune response. Eventually, however, being able to grow a particular monoclonal antibody in a culture dish has become a key area in biotechnology for widespread research, clinical and industrial applications. In 1984, Georges Köhler and César Milstein were awarded the Nobel Prize in Medicine for their Nature publication ‘Continuous cultures of fused cells secreting antibody of predefined specificity’ (Nature 256:495-97)’, describing a method that worked to produce human monoclonal antibodies in culture. However, many other researchers contributed to this revolutionary technology. Hilary Koprowski and Zenon Steplewski were pioneers in cell fusion. Jerrold Schwaber who in 1973 published In Nature along with Edward Cohen, "Human x Mouse Somatic Cell Hybrid Clones Secreting Immunoglobulins of Both Parental Types," (Nature 244:444). This reported another way to produce antibodies in culture, albeit with less specificity.
The identification and study of stem cells in our body would not have been possible without these crucial discoveries. How we can understand human embryonic stem cells or iPS cells is also reliant on these tools. Both Köhler and Milstein recognised the relevance of their method for future applications. In their 1975 Nature paper, they wrote ‘such cultures could be valuable for medical and industrial use.’ However, in his Nobel Prize acceptance speech, César Milstein made it clear that although a decade later, monoclonal antibody technology had become a major product for biotechnology, its existence is rooted in the basic research that set out to answer important questions about our body’s immune system. “The hybridoma technology was a by-product of basic research. Its success in practical applications is to a large extent the result of unexpected and unpredictable properties of the method. It thus represents another clear-cut example of the enormous practical impact of an investment in research which might not have been considered commercially worthwhile, or of immediate medical relevance. It resulted from esoteric speculations, for curiosity’s sake, only motivated by a desire to understand nature.”