Embryo Project Encyclopedia

Telomeres are sequences of DNA on the ends of chromosomes that protect chromosomes from sticking to each other or tangling, which could cause irregularities in normal DNA functions. As cells replicate, telomeres shorten at the end of chromosomes, which correlates to senescence or cellular aging. Integral to this process is telomerase, which is an enzyme that repairs telomeres and is present in various cells in the human body, especially during human growth and development. Telomeres and telomerase are required for normal human embryonic development because they protect DNA as it completes multiple rounds of replication.

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.

Carol Widney Greider studied telomeres and telomerase in the US at the turn of the twenty-first century. She worked primarily at the University of California, Berkeley in Berkeley, California.
She received the Nobel Prize in Physiology or Medicine in 2009, along with Elizabeth Blackburn and Jack Szostak, for their research on telomeres and telomerase. Telomeres are repetitive sequences of
DNA at the ends of chromosomes that protect chromosomes from tangling, and they provide some protection from mutations. Greider also studied telomerase, an enzyme that repairs telomeres. Without telomeres, chromosomes are subject to mutations that can lead to
cell death, and without telomerase, cells might not reproduce fast enough during embryonic development. Greider's research on telomeres helped scientists explain how chromosomes function within cells.

Telomerase is an enzyme that regulates the lengths of telomeres in the cells of many organisms, and in humans it begins to function int the early stages of embryonic development. Telomeres are repetitive sequences of DNA on the ends of chromosomes that protect chromosomes from sticking to each other or tangling. In 1989, Gregg Morin found that telomerase was present in human cells. In 1996, Woodring Wright and his team examined human embryonic cells and found that telomerase was active in them. Scientists manipulate telomerase in cells to give cells the capacity to replicate infinitely. Telomerase is also necessary for stem cells to replicate themselves and to develop into more specialized cells in embryos and fetuses.

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. In the experiment, Hayflick refuted Alexis Carrel's hypothesis that cells could be transplanted and multiplied indefinitely from a single parent cell line.

William Thornton Mustard was a surgeon in Canada during the twentieth century who developed surgical techniques to treat children who had congenital heart defects. Mustard has two surgeries named after him, both of which he helped to develop. The first of these surgeries replaces damaged or paralyzed muscles in individuals who have polio, a virus that can cause paralysis. The other technique corrects a condition called the transposition of the great arteries (TGA) that is noticed at birth. Surgeons worldwide adopted that technique, leading to increased survival rates in infants afflicted with the condition. Mustard also published over 100 articles on congenital heart defects, surgical techniques, and the preparation of an artificial heart lung machine. Mustard helped perform the first blood transfusion of a newborn whose red blood cells (RBCs) had degraded, a condition called hemolytic anemia. Throughout his career, Mustard developed surgical techniques that increased the survival rates of infants and children with congenital and developmental disorders.

The Mustard Operation is a surgical technique to correct a heart condition called the transposition of the great arteries (TGA). TGA is a birth defect in which the placement of the two arteries, the pulmonary artery, which supplies deoxygenated blood to the lungs, and the aorta, which takes oxygenated blood to the body are switched. William Thornton Mustard developed the operation later named for him and in 1963 operated on an infant with TGA, and ameliorated the condition, at the Hospital for Sick Children in Toronto, Canada. Afterwards, the Mustard Operation became the primary form of corrective surgery for TGA, until the arterial switch operation largely replaced the Mustard Operation by the late 1990s. The Mustard Operation enabled surgeons to correct TGA in infants born with the life-threatening anomaly, increasing their life spans and quality of life.

In the 1990s, Ian Wilmut, Jim McWhir, and Keith Campbell performed experiments while working at the Roslin Institute in Roslin, Scotland. Wilmut, McWhir, and Campbell collaborated with Angelica Schnieke and Alex J. Kind at PPL Therapeutics in Roslin, a company researching cloning and genetic manipulation for livestock. Their experiments resulted in several sheep being born in July 1996, one of which was a sheep named Dolly born 5 July 1996. Dolly was the first sheep cloned and developed from the nuclei of fully differentiated adult cells, rather than from the nuclei of early embryonic cells. They published their results in Viable Offspring Derived from Fetal and Adult Mammalian Cells (abbreviated Viable Offspring) on 27 February 1997.

When cells-but not DNA-from two or more genetically distinct individuals combine to form a new individual, the result is called a chimera. Though chimeras occasionally occur in nature, scientists have produced chimeras in a laboratory setting since the 1960s. During the creation of a chimera, the DNA molecules do not exchange genetic material (recombine), unlike in sexual reproduction or in hybrid organisms, which result from genetic material exchanged between two different species. A chimera instead contains discrete cell populations with two unique sets of parental genes. Chimeras can occur when two independent organisms fuse at a cellular level to form one organism, or when a population of cells is transferred from one organism to another. Chimeras created in laboratories have helped scientists to identify developmental mechanisms and processes across species. Some experiments involving chimeras aim to provide further knowledge of immune reactions against disease or to create animal models to understand human disease.

The Hayflick Limit is a concept that helps to explain the
mechanisms behind cellular aging. The concept states that a normal human
cell can only replicate and divide forty to sixty times before it
cannot divide anymore, and will break down by programmed cell death
or apoptosis. The concept of the Hayflick Limit revised Alexis
Carrel's earlier theory, which stated that cells can replicate
themselves infinitely. Leonard Hayflick developed the concept while
at the Wistar Institute in Philadelphia,
Pennsylvania, in 1965. In his 1974 book Intrinsic
Mutagenesis, Frank Macfarlane Burnet named the concept after
Hayflick. The concept of the Hayflick Limit helped scientists study
the effects of cellular aging on human populations from embryonic
development to death, including the discovery of the effects of
shortening repetitive sequences of DNA, called telomeres, on the
ends of chromosomes. Elizabeth Blackburn, Jack Szostak and Carol
Greider received the Nobel Prize in Physiology or Medicine in 2009
for their work on genetic structures related to the Hayflick
Limit.