Stem cell
In the early 1960s, Ernest McCulloch and James Till conducted experiments at the University of Toronto that changed how scientists understood cell division. They injected bone marrow cells into irradiated mice and observed lumps forming in the spleens. These lumps were linearly proportional to the number of cells injected. Each lump represented a clone arising from a single stem cell. This discovery established two core properties: self-renewal and potency. Self-renewal allows a cell to divide indefinitely while maintaining its undifferentiated state. Potency refers to the capacity to differentiate into specialized cell types. A stem cell can become any tissue in the body if given sufficient stimulation. Embryonic stem cells are pluripotent, meaning they can develop into more than 200 different cell types. Adult stem cells are multipotent or unipotent, limiting them to specific lineages like blood or skin. Hematopoietic stem cells replenish blood and immune cells throughout life. Mesenchymal stem cells maintain bone, cartilage, muscle, and fat tissues. The distinction between these cell types lies in their ability to proliferate without losing their identity. Progenitor cells cannot divide indefinitely, which sets them apart from true stem cells.
The term stem cell was coined by Theodor Boveri and Valentin Haecker in the late 19th century. Pioneering work on blood stem cells began at the start of the 20th century with Artur Pappenheim and Alexander A. Maximow. In 1956, French oncologist Georges Mathé performed the first therapy using stem cells on five workers at the Vinča Nuclear Institute in Yugoslavia. These workers had suffered a criticality accident and all survived after receiving bone marrow transplants. Canadian biologists Ernest McCulloch and James Till published their findings in Nature in 1963, confirming that each spleen colony arose from a single cell. British biologists Martin Evans and Matthew Kaufman isolated embryonic stem cells from mouse blastocysts in 1981. This allowed researchers to create murine genetic models for studying pathology. Ann Tsukamoto patented a process for isolating human stem cells in 1991. American biologist James Thomson successfully cultured human embryonic stem cells in 1998. This breakthrough made it possible to develop new transplantation methods and test treatments. In 2006, Shinya Yamanaka's team in Kyoto converted fibroblasts into pluripotent stem cells by modifying four genes. The feat marked the origin of induced pluripotent stem cells.
Human embryonic stem cells originate as inner cell mass within a blastocyst formed 4, 5 days after fertilization. These cells consist of 50 to 150 cells during this stage. They are pluripotent and give rise to all derivatives of the three germ layers: ectoderm, endoderm, and mesoderm. Embryonic stem cells do not contribute to extraembryonic membranes or the placenta. Adult stem cells exist in select locations called niches such as bone marrow or gonads. Hematopoietic stem cells replenish blood and immune cells while basal cells maintain skin epithelium. Mesenchymal stem cells support bone, cartilage, muscle, and fat tissues. Adult stem cells are multipotent or unipotent, meaning they differentiate into only a few cell types. They are vastly outnumbered by progenitor cells and terminally differentiated cells. Research on adult stem cells is less controversial because it does not require destroying an embryo. Autologous harvesting from one's own body carries minimal risk of rejection. Bone marrow transplants have been used for over 50 years to treat leukemia and lymphoma. Umbilical cord blood provides another source of hematopoietic stem cells. The quantity of bone marrow stem cells declines with age and varies between males and females.
Shinya Yamanaka led a Japanese team at Kyoto University that discovered a method to convert mature body cells back into stem cells in 2006. They used transcription factors Oct3/4, Sox2, c-Myc, and Klf4 to reprogram mouse fibroblast cells. Subsequent work applied these factors to human fibroblast cells. Junying Yu and James Thomson used different factors including Nanog and Lin28 to induce pluripotency in human foreskin cells. Induced pluripotent stem cells share properties like pluripotency and differentiation potential with embryonic stem cells. However, their chromatin appears more closed or methylated than embryonic counterparts. Gene expression patterns differ slightly between the two cell types. Despite this, inducing somatic cells to be pluripotent remains viable. Ian Wilmut announced he would abandon somatic cell nuclear transfer as research after learning about Yamanaka's work. His inspiration came from creating human embryo stem cells without needing human eggs or destroying cloned embryos. Patient-specific stem lines allow for reduced risk of transplantation rejection. Frozen blood samples can serve as valuable sources for induced pluripotent stem cells. These cells hold great potential for future medical treatments.
Bone marrow transplant is the only established therapy using stem cells as of 2009. It has been used for over 50 years to treat leukemia and lymphoma. Hematopoietic stem cell transplantation usually takes the form of bone-marrow transplantation but can also derive from umbilical cord blood. Research continues to develop various sources for stem cells and apply treatments to neurodegenerative diseases. Conditions under investigation include diabetes, heart disease, spinal cord injury repair, and Parkinson's disease. The first human trial approved by the US Food and Drug Administration occurred in January 2009. This trial began on the 13th of October 2010, in Atlanta for spinal cord injury research. Geron Corporation discontinued further development of its stem cell programs on the 14th of November 2011. Differentiating embryonic stem cells into usable cells while avoiding transplant rejection remains a major hurdle. Pluripotency linked to tumor formation poses risks especially with embryonic or fetal proper stem cells. Some stem cells form tumors after transplantation due to their ability to create tissues other than desired types. Stem cell tourism involves patients traveling to obtain unproven procedures that may cause complications like spinal tumors or death.
Deriving embryonic stem cells typically results in the destruction of early-stage embryos. Critics argue this practice violates the sanctity of human life. Central to the debate is the moral status of the human embryo. Roman Catholic teaching forbids using embryonic stem cells in experimentation. The Vatican newspaper Osservatore Romano called amniotic stem cells the future of medicine. In the United States, Executive Order 13505 established federal funding criteria for approved human embryonic stem-cell lines. The National Institutes of Health implemented guidelines effective the 7th of July 2009. There were 486 approved lines as of January 2022. Fundamental patents covering human embryonic stem cells are owned by the Wisconsin Alumni Research Foundation. James A. Thomson invented patents numbered 5,843,780, 6,200,806, and 7,029,913. Consumer Watchdog filed a request for re-examination of these patents in 2006. The US Patent and Trademark Office initially rejected all claims but later found amended claims patentable in 2008. The case continued through appeals until January 2013 when amended claims were allowed. Some nations have moratoria or limitations on human embryonic stem cell research due to ethical controversies.
Common questions
Who discovered stem cells and when was the term coined?
Theodor Boveri and Valentin Haecker coined the term stem cell in the late 19th century. Ernest McCulloch and James Till conducted experiments at the University of Toronto in the early 1960s that established core properties like self-renewal and potency.
What are the different types of stem cells and their specific functions?
Embryonic stem cells are pluripotent and can develop into more than 200 different cell types from three germ layers. Adult stem cells include hematopoietic stem cells that replenish blood and immune cells, as well as mesenchymal stem cells that maintain bone, cartilage, muscle, and fat tissues.
When did Shinya Yamanaka discover induced pluripotent stem cells?
Shinya Yamanaka's team in Kyoto converted fibroblasts into pluripotent stem cells by modifying four genes on the 4th of November 2006. This discovery marked the origin of induced pluripotent stem cells which share properties with embryonic stem cells but have closed chromatin.
How many approved human embryonic stem cell lines existed in January 2022?
There were 486 approved lines as of January 2022 according to National Institutes of Health guidelines effective the 7th of July 2009. Executive Order 13505 established federal funding criteria for these approved human embryonic stem-cell lines.
What is the first human trial date for spinal cord injury research using stem cells?
The first human trial approved by the US Food and Drug Administration began on the 13th of October 2010 in Atlanta for spinal cord injury research. Geron Corporation discontinued further development of its stem cell programs on the 14th of November 2011.