Human pluripotent stem cells is a collective term used to describe both human embryonic stem (hES) cells as well as human induced pluripotent stem (iPS) cells.
Human Embryonic Stem Cells
Human embryonic stem cells (hES) Human Embryonic Stem Cells are from a group of cells called the inner cell mass. These cells are part of a 5-6 day old embryo called a blastocyst. When cultured in the laboratory, stem cells have the unique ability to self-replicate or renew themselves for long periods of time. This process can produce a large population of identical cells. For this reason, hES cells are said to be “immortal.” This characteristic of the cells is very valuable for scientists, since they need a large number of cells to conduct their research experiments.
Embryonic stem cells are undifferentiated or “blank slate” cells, meaning that they have not yet acquired a specific role or function. These cells possess all the necessary genetic and cellular equipment to become any of the specific, specialized cells in the entire human body under the right conditions. This ability of the cells is referred to as pluripotency. This quality renders them exceedingly useful for screening potential medications, studying disease patterns, uncovering the details of development, and potentially providing cellular replacement components for regenerative medicine.
Embryonic stem cells are extremely sensitive to their environment and require very strict conditions to thrive in culture as undifferentiated pluripotent cells. Any changes in the environment can cause the cells to differentiate, or acquire the traits and function of a more specialized cell type. Scientists can induce differentiation of hES cells by changing factors in the cells’ environment. The hES cells receive chemical signals from the medium (the liquid in which the cells are cultured) that initiate changes in the cells’ structure and function, causing differentiation.
Stem cell pioneer Dr. James Thomson, Ph.D., V.M.D, was the first to isolate these cells in 1998 and serves as the scientific director of Regenerative Biology at the Morgridge Institute for Research. Scientists on Dr. Thomson’s team as well as others from the University of Wisconsin- Madison (UW-Madison) have made significant contributions to the field of stem cell research, thus leading to a better understanding of human development and cell-based diseases. Microscopic view of hES cell colonies
Induced Pluripotent Stem Cells
Induced pluripotent stem cells (iPS) are created from an adult cell such as a skin cell, through the introduction of specific genes. The genes reprogram the cell into a pluripotent stem cell that exhibit similar characteristics as an embryonic stem cell. Like hES cells, iPS cells are pluripotent and can differentiate into any cell type in the body.
Derivation of iPS cells
The process of creating these cells is known as reprogramming, which involves introducing pluripotent genes (eg. Oct4, Sox2, Nanog, Lin28) into the skin cell via a vector. A vector is any agent that acts as a carrier or transporter, such as a virus or plasmid/s that deliver a genetically engineered DNA segment into a host cell. The new genes start regulating other genes in the skin cell resulting in the reversal of the cell’s developmental clock as the cell replicates. Gradually the new cells acquire properties similar to those of embryonic stem cells.
This work was simultaneously accomplished in 2007 by Dr. James Thomson of UW-Madison and Dr. Shinya Yamanaka of Kyoto University, using viruses to reprogram the cells. This method of creating iPS cells required a viral vector that integrates randomly into the genome of the cell. This technique presented the possibility of creating mutations in the DNA and therefore limiting the utility of the cells in both research and clinical applications.
In 2009, Dr. Thomson and his team created iPS cells that are completely free of viral vectors. This was accomplished by the use of a plasmid (non- integrating episomal vector) rather than the virus to carry the reprogramming genes into the adult cells. The plasmid and the genes it carries do not integrate into the induced cell’s genome and can be screened out of subsequent generations of cells. This is the preferred method because the cells created are completely free of genetic artifacts that could compromise therapeutic safety or skew research results.
Advantages of iPS cells
The method of creating iPS cells eliminates ethical concerns because it does not require the destruction of a blastocyst to create a cell line. A skin sample can be taken from a patient with a disease such as Parkinson’s or diabetes which allows researchers to create stem cell lines that have the characteristics of that disease. These iPS cell lines can act as a disease model to help researchers study the disease at a cellular level and allows for pharmaceutical companies to scan for drug safety and effectiveness.
Applications of Stem Cell Research
Before the advent of human embryonic stem cells, the earliest stages of human development have been difficult or impossible to study. Embryonic stem cells offer insights into developmental events that cannot be studied directly in humans in utero or fully understood through the use of animal models. These cells provide a valuable tool to study problems associated with implantation of the embryos and miscarriages in spontaneous women. Understanding the events that occur at the first stages of development has potential clinical significance for preventing or treating birth defects, infertility and pregnancy loss. A thorough knowledge of normal development could ultimately allow the prevention or treatment of abnormal human development.
Researchers have been successful in obtaining a large number of pure populations of specific cell types from human embryonic stem cells. This pure population of cells can be extremely useful in screening chemical compounds (potential medications) for a variety of diseases or conditions. While traditional methods take several years and millions of dollars for new medications to be available in the market, this method will dramatically reduce the time and costs required to discover new drugs. In the future, the access to stem cell technology would allow scientists to carry out rapid screening of hundreds and thousands of chemicals and compounds in a relatively short time span.
(Cellular Transplantation Therapy)
Regenerative medicine focuses on repairing or replacing diseased or defective cells or tissues in the human body. The human body is only capable of limited self-repair and does so to heal or repair injuries and combat age-related wear and tear of tissues and organs. Diseases like juvenile onset diabetes and Parkinson’s disease are examples of conditions that result from defects in specific cells types in the body.
Parkinson’s disease is caused by the death of a specific type of neuron (dopaminergic neurons). Currently around 1 million people in the U.S. are affected by this condition.
Juvenile onset diabetes is caused by the death of specific pancreatic cells (islet ß cells). According to the U.S Center for Disease Control (CDC) in 2010 approximately 215,000 people under the age of 20 had diabetes.
The following are examples of some of the medical conditions and the number of people in the US affected by each. These and others not yet diagnosed can potentially benefit from stem cell-based therapies.
|Cardiovascular disease||81.1 million|
|Alzheimer’s disease||5 million|
|Parkinson’s disease||1 million|
|Spinal-cord injuries||0.20 million|
|Birth defects||3% of all babies born|
Source: Centers for Disease Control and
Parkinson’s Disease Foundation.
Scientists conducting research in the area of stem cells address a variety of questions from the basics of understanding the parameters of pluripotency to studying specific signals that allow differentiation of these cells within the human body. These research advancements have contributed towards a better understanding of the molecular mechanisms critical to the control of pluripotency and understanding the differentiation process in embryonic stem cells.