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Hanging Drop Tissue Culture

The hanging drop tissue culture is a technique utilized in embryology and other fields to allow growth that would otherwise be restricted by the flat plane of culture dishes and also to minimize the surface area to volume ratio, slowing evaporation. The classic hanging drop culture is a small drop of liquid, such as plasma or some other media allowing tissue growth, suspended from an inverted watch glass. The hanging drop is then suspended by gravity and surface tension, rather than spreading across a plate.

Format: Articles

Subject: Technologies

“A Two-Factor Hypothesis of Freezing Injury: Evidence from Chinese Hamster Tissue-Culture Cells” (1972), by Peter Mazur, Stanley Leibo, and Ernest Chu

In 1972, Peter Mazur, Stanley Leibo, and Ernest Chu published, “A Two-Factor Hypothesis of Freezing Injury: Evidence from Chinese Hamster Tissue-culture Cells,” hereafter, “A Two-Factor Hypothesis of Freezing Injury,” in the journal, Experimental Cell Research. In the article, the authors uncover that exposure to high salt concentrations and the formation of ice crystals within cells are two factors that can harm cells during cryopreservation. Cryopreservation is the freezing of cells to preserve them for storage, study, or later use.

Format: Articles

Subject: Publications, Theories

Ross Granville Harrison (1870-1959)

A pioneer in experimental embryology, Ross Granville Harrison made numerous discoveries that advanced biology. One of the most significant was his adaptation of the hanging drop method from bacteriology to carry out the first tissue culture. This method allowed for further studies in embryology as well as experimental improvements in oncology, virology, genetics, and a number of other fields.

Format: Articles

Subject: People

Alexis Carrel's Tissue Culture Techniques

Alexis Carrel, the prominent French surgeon, biologist, and 1912 Nobel Prize laureate for Physiology or Medicine, was one of the pioneers in developing and modifying tissue culture techniques. The publicized work of Carrel and his associates at the Rockefeller Institute established the practice of long-term tissue culture for a wide variety of cells. At the same time, some aspects of their work complicated the operational procedures of tissue culture.

Format: Articles

Subject: Technologies

"The Outgrowth of the Nerve Fiber as a Mode of Protoplasmic Movement" (1910), by Ross Granville Harrison

In "The Outgrowth of the Nerve Fiber as a Mode of Protoplasmic Movement," Ross Granville Harrison explores the growth of nerve fibers in vitro. The purpose of this experiment was to test two possible hypotheses for the growth of nerve fibers. Santiago Ramón y Cajal suggested that nerve growth is due to the extension of nerve fibers as they push through tissue. Victor Hensen's syncytial theory proposed an opposing view of nerve growth.

Format: Articles

Subject: Experiments

"On the Permanent Life of Tissues outside of the Organism" (1912), by Alexis Carrel

'On the Permanent Life of Tissues outside of the Organism' reports Alexis Carrel's 1912 experiments on the maintenance of tissue in culture media. At the time, Carrel was a French surgeon and biologist working at the Rockefeller Institute in New York City. In his paper, Carrel reported that he had successfully maintained tissue cultures, which derived from connective tissues of developing chicks and other tissue sources, by serially culturing them.

Format: Articles

Subject: Experiments

Thesis: Socioeconomic and Cultural Ideas of Endometriosis in Low and Middle-Income Countries: A Narrative Literature Review

Endometriosis is a condition characterized by the growth of the endometrium, or the tissue that lines the uterus, outside of the uterus, and it is diagnosed through the presence of endometriotic lesions in the pelvic region. The disease is most often associated with abnormal and painful vaginal bleeding.

Format: Essays and Theses

Subject: Disorders, Places, Outreach

Alexis Carrel's Immortal Chick Heart Tissue Cultures (1912-1946)

In an effort to develop tissue culture techniques for long-term tissue cultivation, French surgeon and biologist Alexis Carrel, and his associates, produced and maintained a series of chick heart tissue cultures at the Rockefeller Institute in New York City. From 1912 to 1946, this series of chick heart tissue cultures remained alive and dividing. Since the duration of this culture greatly exceeded the normal chick life span, the cells were deemed immortal.

Format: Articles

Subject: Experiments

Reassessment of Carrel's Immortal Tissue Culture Experiments

In the 1910s, Alexis Carrel, a French surgeon and biologist, concluded that cells are intrinsically immortal. His claim was based on chick-heart tissue cultures in his laboratory that seemed to be able to proliferate forever. Carrel's ideas about cellular immortality convinced his many contemporaries that cells could be maintained indefinitely. In the 1960s, however, Carrel's thesis about cell immortality was put into question by the discovery that human diploid cells can only proliferate for a finite period.

Format: Articles

Subject: Processes, Theories

Alexis Carrel (1873-1944)

Alexis Carrel was a doctor and researcher who studied tissue cultures. He continued Ross Granville Harrison's research and produced many improvements in the field of tissue culture and surgery. He was the recipient of the 1912 Nobel Prize in Physiology or Medicine for his development of surgical techniques to repair blood vessels. Carrel was born on 28 June 1873 in Sainte-Foy-les-Lyon, France, to Anne-Marie Ricard and Alexis Carrel Billiard. His father died when he was five years old.

Format: Articles

Subject: People

Leo Loeb (1869-1959)

Leo Loeb developed an experimental approach to studying cancer and pioneered techniques for tissue culture and in vitro tissue transplantation which impacted early-to-mid twentieth century experimental embryology. Loeb received his medical degree from the University of Zurich in 1897. As part of his doctorate, he completed a thesis on the outcomes of tissue transplantation in guinea pigs. Loeb's thesis inspired a life-long interest in tissue transplantation.

Format: Articles

Subject: People

Leonard Hayflick (1928- )

Leonard Hayflick studied the processes by which cells age during the twentieth and twenty-first centuries in the United States. In 1961 at the Wistar Institute in the US, Hayflick researched a phenomenon later called the Hayflick Limit, or the claim that normal human cells can only divide forty to sixty times before they cannot divide any further. Researchers later found that the cause of the Hayflick Limit is the shortening of telomeres, or portions of DNA at the ends of chromosomes that slowly degrade as cells replicate.

Format: Articles

Subject: People

Tissue Engineering

Tissue engineering is a field of regenerative medicine that integrates the knowledge of scientists, physicians, and engineers into the construction or reconstruction of human tissue. Practitioners of tissue engineering seek to repair, replace, maintain, and enhance the abilities of a specific tissue or organ by means of living cells. More often than not stem cells are the form of living cells used in this technology. Tissue engineering is one of the disciplines involved in translating knowledge of developmental biology into the clinical setting.

Format: Articles

Subject: Processes

Beadle and Ephrussi's Transplantation Technique for Drosophila

Boris Ephrussi and George Wells Beadle developed a transplantation technique on flies, Drosophila melanogaster, which they described in their 1936 article A Technique of Transplantation for Drosophila. The technique of injecting a tissue from one fly larva into another fly larva, using a micropipette, to grow that tissue in the second larvae, was a means for investigating development of Drosophila. Through this technique, Beadle and Ephrussi studied the role of genes in embryological processes.

Format: Articles

Subject: Technologies

Boris Ephrussi (1901-1979)

Boris Ephrussi studied fruit flies, yeast, and mouse genetics and development while working in France and the US during the twentieth century. In yeast, Ephrussi studied how mutations in the cytoplasm persisted across generations. In mice he studied the genetics of hybrids and the development of cancer. Working with George Wells Beadle on the causes of different eye colors in fruit flies, Ephrussi's research helped establish the one-gene-one-enzyme hypothesis. Ephrussi helped create new embryological techniques and contributed the theories of genetics and development.

Format: Articles

Subject: People

George Otto Gey (1899-1970)

George Otto Gey was a scientist in the US who studied cells and cultivated the first continuous human cell line in 1951. Gey derived the cells for that cell line, called the HeLa cell line, from a woman called Henrietta Lacks, a Black woman who had cervical cancer. Cell lines are a cluster of cells that continuously multiply on their own outside of the organism from which they originated. Gey developed new techniques for in vitro, or laboratory-based, maintenance of organs and hormonal tissue, created new methods for cell cultivation, and researched nutritional media, or cell food.

Format: Articles

Subject: People

Epithelium

Frederik Ruysch, working in the Netherlands, introduced the term epithelia in the third volume of his Thesaurus Anatomicus in 1703. Ruysch created the term from the Greek epi, which means on top of, and thele, which means nipple, to describe the type of tissue he found when dissecting the lip of a cadaver. In the mid nineteenth century, anatomist Albrecht von Haller adopted the word epithelium, designating Ruysch's original terminology as the plural version. In modern science, epithelium is a type of animal tissue in which cells are packed into neatly arranged sheets.

Format: Articles

Subject: Theories, Processes

"The Limited In Vitro Lifetime of Human Diploid Cell Strains" (1964), by Leonard Hayflick

Leonard Hayflick in the US during the early 1960s showed that normal populations of embryonic cells divide a finite number of times. He published his results as 'The Limited In Vitro Lifetime of Human Diploid Cell Strains' in 1964. Hayflick performed the experiment with WI-38 fetal lung cells, named after the Wistar Institute, in Philadelphia, Pennsylvania, where Hayflick worked. Frank MacFarlane Burnet, later called the limit in capacity for cellular division the Hayflick Limit in 1974.

Format: Articles

Subject: Experiments

"In vitro Experiments on the Effects of Mouse Sarcomas 180 and 37 on the Spinal and Sympathetic Ganglia of the Chick Embryo" (1954), by Rita Levi-Montalcini, Viktor Hamburger, and Hertha Meyer

"In vitro Experiments on the Effects of Mouse Sarcomas 180 and 37 on the Spinal and Sympathetic Ganglia of the Chick Embryo" were experiments conducted by Rita Levi-Montalcini in conjunction with Viktor Hamburger and Hertha Meyer and published in Cancer Research in 1954. In this series of experiments, conducted at the University of Brazil, Levi-Montalcini demonstrated increased nerve growth by introducing specific tumors (sarcomas) to chick ganglia. Ganglia are clusters of nerve cells, from which nerve fibers emerge.

Format: Articles

Subject: Experiments

Serial Cultivation of Human Diploid Cells in the Lab (1958–1961) by Leonard Hayflick and Paul S. Moorhead

From 1958 to 1961, Leonard Hayflick and Paul Moorhead in the US developed a way in the laboratory to cultivate strains of human cells with complete sets of chromosomes. Previously, scientists could not sustain cell cultures with cells that had two complete sets of chromosomes like normal human cells (diploid). As a result, scientists struggled to study human cell biology because there was not a reliable source of cells that represented diploid human cells. In their experiments, Hayflick and Moorhead created lasting strains of human cells that retained both complete sets of chromosomes.

Format: Articles

Subject: Experiments

“Survival of Mouse Embryos Frozen to -196 ° and -269 °C” (1972), by David Whittingham, Stanley Leibo, and Peter Mazur

In 1972, David Whittingham, Stanley Leibo, and Peter Mazur published the paper, “Survival of Mouse Embryos Frozen to -196 ° and -269 °C,” hereafter, “Survival of Mouse Embryos,” in the journal Science. The study marked one of the first times that researchers had successfully cryopreserved, or preserved and stored by freezing, a mammalian embryo and later transferred that embryo to a live mouse who gave birth to viable offspring. Previously, scientists had only been successful cryopreserving single cells, like red blood cells.

Format: Articles

Subject: Experiments, Publications

"Derivation of Pluripotent Stem Cells from Cultured Human Primordial Germ Cells" (1998), by John Gearhart et al.

In November 1998, two independent reports were published concerning the first isolation of pluripotent human stem cells, one of which was "Derivation of Pluripotent Stem Cells from Cultured Human Primordial Germ Cells." This paper, authored by John D. Gearhart and his research team - Michael J Shamblott, Joyce Axelman, Shunping Wang, Elizabeith M. Bugg, John W. Littlefield, Peter J. Donovan, Paul D. Blumenthal, and George R. Huggins - was published in Proceedings of the National Academy of Science soon after James A.

Format: Articles

Subject: Publications

"Purification of a Nerve-Growth Promoting Protein from the Mouse Salivary Gland and its Neuro-Cytoxic Antiserum" (1960), by Stanley Cohen

Stanley Cohen published "Purification of a Nerve-Growth Promoting Protein from the Mouse Salivary Gland and its Neuro-Cytoxic Antiserum" in the Proceedings of the National Academies of Sciences in 1960. This paper outlined the successful purification and identification of nerve growth factor (NGF) as a protein, the developmental effects of depriving an embryo of NGF, and the discovery that NGF is also required for the maintenance of the nervous system.

Format: Articles

Subject: Experiments

Stanley Alan Plotkin's Development of a Rubella Vaccine (1969)

In the US during the late 1960s, Stanley Alan Plotkin, John D. Farquhar, Michael Katz, and Fritz Buser isolated a strain of the infectious disease rubella and developed a rubella vaccine with a weakened, or attenuated, version of the virus strain. Rubella, also called German measles, is a highly contagious disease caused by the rubella virus that generally causes mild rashes and fever. However, in pregnant women, rubella infections can lead to developmental defects in their fetuses.

Format: Articles

Subject: Experiments

Thesis: A History of Cellular Senescence and Its Relation to Stem Cells in the Twentieth and Twenty-First Centuries

This study aims to provide information to answer the following question: While some scientists claim they can indefinitely culture a stem cell line in vitro, what are the consequences of those culturing practices? An analysis of a cluster of articles from the Embryo Project Encyclopedia provides information to suggest possible solutions to some potential problems in cell culturing, recognition of benefits for existing or historical culturing practices, and identification of gaps in scientific knowledge that warrant further research.

Format: Essays and Theses

Subject: Processes, Publications

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