Stem cell
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell in a cell lineage.[1] They are found in both embryonic and adult organisms, but they have slightly different properties in each. They are usually distinguished from progenitor cells, which cannot divide indefinitely, and precursor or blast cells, which are usually committed to differentiating into one cell type.
This article is about the cell type. For the medical therapy, see stem-cell therapy.Stem cell
In mammals, roughly 50 to 150 cells make up the inner cell mass during the blastocyst stage of embryonic development, around days 5–14. These have stem-cell capability. In vivo, they eventually differentiate into all of the body's cell types (making them pluripotent). This process starts with the differentiation into the three germ layers – the ectoderm, mesoderm and endoderm – at the gastrulation stage. However, when they are isolated and cultured in vitro, they can be kept in the stem-cell stage and are known as embryonic stem cells (ESCs).
Adult stem cells are found in a few select locations in the body, known as niches, such as those in the bone marrow or gonads. They exist to replenish rapidly lost cell types and are multipotent or unipotent, meaning they only differentiate into a few cell types or one type of cell. In mammals, they include, among others, hematopoietic stem cells, which replenish blood and immune cells, basal cells, which maintain the skin epithelium, and mesenchymal stem cells, which maintain bone, cartilage, muscle and fat cells. Adult stem cells are a small minority of cells; they are vastly outnumbered by the progenitor cells and terminally differentiated cells that they differentiate into.[1]
Research into stem cells grew out of findings by Canadian biologists Ernest McCulloch, James Till and Andrew J. Becker at the University of Toronto and the Ontario Cancer Institute in the 1960s.[2][3] As of 2016, the only established medical therapy using stem cells is hematopoietic stem cell transplantation,[4] first performed in 1958 by French oncologist Georges Mathé. Since 1998 however, it has been possible to culture and differentiate human embryonic stem cells (in stem-cell lines). The process of isolating these cells has been controversial, because it typically results in the destruction of the embryo. Sources for isolating ESCs have been restricted in some European countries and Canada, but others such as the UK and China have promoted the research.[5] Somatic cell nuclear transfer is a cloning method that can be used to create a cloned embryo for the use of its embryonic stem cells in stem cell therapy.[6] In 2006, a Japanese team led by Shinya Yamanaka discovered a method to convert mature body cells back into stem cells. These were termed induced pluripotent stem cells (iPSCs).[7]
History[edit]
The term stem cell was coined by Theodor Boveri and Valentin Haecker in late 19th century.[8] Pioneering works in theory of blood stem cell were conducted in the beginning of 20th century by Artur Pappenheim, Alexander Maximow, Franz Ernst Christian Neumann.[8]
The key properties of a stem cell were first defined by Ernest McCulloch and James Till at the University of Toronto and the Ontario Cancer Institute in the early 1960s. They discovered the blood-forming stem cell, the hematopoietic stem cell (HSC), through their pioneering work in mice. McCulloch and Till began a series of experiments in which bone marrow cells were injected into irradiated mice. They observed lumps in the spleens of the mice that were linearly proportional to the number of bone marrow cells injected. They hypothesized that each lump (colony) was a clone arising from a single marrow cell (stem cell). In subsequent work, McCulloch and Till, joined by graduate student Andrew John Becker and senior scientist Louis Siminovitch, confirmed that each lump did in fact arise from a single cell. Their results were published in Nature in 1963. In that same year, Siminovitch was a lead investigator for studies that found colony-forming cells were capable of self-renewal, which is a key defining property of stem cells that Till and McCulloch had theorized.[9]
The first therapy using stem cells was a bone marrow transplant performed by French oncologist Georges Mathé in 1956 on five workers at the Vinča Nuclear Institute in Yugoslavia who had been affected by a criticality accident. The workers all survived.[10]
In 1981, embryonic stem (ES) cells were first isolated and successfully cultured using mouse blastocysts by British biologists Martin Evans and Matthew Kaufman. This allowed the formation of murine genetic models, a system in which the genes of mice are deleted or altered in order to study their function in pathology. By 1998, human embryonic stem cells were first isolated by American biologist James Thomson, which made it possible to have new transplantation methods or various cell types for testing new treatments. In 2006, Shinya Yamanaka's team in Kyoto, Japan converted fibroblasts into pluripotent stem cells by modifying the expression of only four genes. The feat represents the origin of induced pluripotent stem cells, known as iPS cells.[7]
In 2011, a female maned wolf, run over by a truck, underwent stem cell treatment at the Zoo Brasília, this being the first recorded case of the use of stem cells to heal injuries in a wild animal.[11][12]
Amniotic[edit]
Also called perinatal stem cells, these multipotent stem cells are found in amniotic fluid and umbilical cord blood. These stem cells are very active, expand extensively without feeders and are not tumorigenic. Amniotic stem cells are multipotent and can differentiate in cells of adipogenic, osteogenic, myogenic, endothelial, hepatic and also neuronal lines.[66]
Amniotic stem cells are a topic of active research.
Use of stem cells from amniotic fluid overcomes the ethical objections to using human embryos as a source of cells. Roman Catholic teaching forbids the use of embryonic stem cells in experimentation; accordingly, the Vatican newspaper "Osservatore Romano" called amniotic stem cells "the future of medicine".[67]
It is possible to collect amniotic stem cells for donors or for autologous use: the first US amniotic stem cells bank[68][69] was opened in 2009 in Medford, MA, by Biocell Center Corporation[70][71][72] and collaborates with various hospitals and universities all over the world.[73]
Notable studies[edit]
In August 2021, researchers in the Princess Margaret Cancer Centre at the University Health Network published their discovery of a dormancy mechanism in key stem cells which could help develop cancer treatments in the future.[148]