induced pluripotent stem cell
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What is an induced pluripotent stem cell?
An induced pluripotent stem cell (iPS cell) is an immature cell generated from a mature adult cell that has regained its ability to differentiate into any type of cell in the body. iPS cells are created by introducing regulatory genes into adult cells, which reprograms them to a pluripotent state.
iPS cells resemble embryonic stem cells but, unlike embryonic stem cells, iPS cells can be obtained without the ethical concerns of using embryos. iPS cells can be stimulated to differentiate into specific cell types for disease treatments and for modeling diseases in the lab.
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How are induced pluripotent stem cells made?
Induced pluripotent stem cells (iPS cells) are created by reprogramming mature adult cells to revert to an immature state where they can differentiate into any type of cell in the body. This is achieved by introducing pluripotency factors, such as the transcription factors Oct-4 and Sox-2, into non-pluripotent cells.
The pluripotency factors are delivered into adult cells using methods such as plasmids or modified RNAs, but the most effective method is delivery via retroviral vectors. The retroviruses transport the RNA of regulatory genes into the nuclei of the adult cells, where the genes are then incorporated into the DNA of the cells, which reprograms the adult cells into iPS cells.
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Why are these stem cells called 'pluripotent'?
The term 'pluripotent' refers to a cell's ability to differentiate into many cell types, but not all. Induced pluripotent stem cells (iPS cells) are called this because they are generated from mature cells and regain the capacity to differentiate into any cell type in the body, similar to embryonic stem cells. This pluripotency is achieved by introducing regulatory genes into adult cells, effectively reprogramming them to an embryonic stem cell-like state. The advantage of using iPS cells is that their creation doesn't require an embryo, which circumvents ethical concerns.
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How do induced pluripotent stem cells differ from embryonic stem cells?
Induced pluripotent stem cells (iPS cells) and embryonic stem cells (ES cells) are both pluripotent, but they differ in origin. iPS cells are generated from adult, mature cells that are reprogrammed to regain the ability to differentiate into any cell type in the body. This reprogramming is achieved by introducing specific regulatory genes into adult cells.
ES cells, on the other hand, are derived from the inner cell mass of a mammalian embryo at a very early stage of development (blastocyst). A key advantage of iPS cells is that their creation doesn't require the use of an embryo, which circumvents ethical concerns associated with embryonic stem cells.
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What are some ways scientists use induced pluripotent stem cells in research or medicine?
Scientists use induced pluripotent stem cells (iPS cells) in research and medicine to understand cell differentiation and explore disease treatment. iPS cells can be created from a patient's own adult cells to generate matched cells and tissues for transplantation therapies, overcoming immune rejection risks.
Researchers also use iPS cells to create human blastoids, which help in understanding pregnancy and pregnancy loss by replicating early embryonic development events. iPS cells are also being explored as models for disease mechanisms and drug screening. For example, neurons and cardiomyocytes derived from human iPS cells have shown promise in promoting recovery of stroke-damaged brain tissue and integrating into damaged heart tissue in animal models.
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What are some advantages and challenges of using induced pluripotent stem cells in treating diseases?
Induced pluripotent stem cells (iPS cells) are created from adult cells and can differentiate into any cell type, similar to embryonic stem cells. An advantage of iPS cells is the potential to create patient-specific cells, reducing the risk of immune rejection in regenerative medicine.
However, generating reprogrammed cells requires a retrovirus, potentially introducing harmful, cancer-causing viruses into patients. Further research is needed to fully understand how to control the proliferation, migration, differentiation, and survival of neural stem cells and their progeny.
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induced pluripotent stem cell (iPS cell), immature cell that is generated from an adult (mature) cell and that has regained the capacity to differentiate into any type of cell in the body. Induced pluripotent stem cells (iPS cells) differ from embryonic stem cells (ES cells), which form the inner cell mass of an embryo but also are pluripotent, eventually giving rise to all the cell types that make up the body. Induced pluripotent cells were first described in 2006 by Japanese physician and researcher Shinya Yamanaka and colleagues. The first experiments were performed by using mouse cells. The following year, however, Yamanaka successfully derived iPS cells from human adult fibroblast cells. Until that time, human stem cells could be obtained only by isolating them from early human embryos. Hence, an important feature of iPS cells is that their generation does not require an embryo, the use of which is fraught with ethical issues.
Early developments
The generation of iPS cells from somatic cells (fully differentiated adult cells, excluding germ cells) was based on the idea that any cell in the body can be “reprogrammed” to a more primitive (stemlike) state. Among the first to discover that possibility was British developmental biologist John B. Gurdon, who in the late 1950s had shown in frogs that egg cells are able to reprogram differentiated cell nuclei. Gurdon used a technique known as somatic cell nuclear transfer (SCNT), in which the nucleus of a somatic cell is transferred into the cytoplasm of an enucleated egg (an egg that has had its nucleus removed). In 1996 British developmental biologist Ian Wilmut and colleagues used SCNT to create Dolly the sheep, the first clone of an adult mammal. The experiments with SCNT were crucial to the eventual production of iPS cells. Indeed, by the time of Dolly’s creation, it was widely accepted that factors in the egg cytoplasm were responsible for reprogramming differentiated cell nuclei. The factors controlling the process were unknown, however, until Yamanaka published his first report describing iPS cell generation. (Yamanaka and Gurdon shared the 2012 Nobel Prize for Physiology or Medicine for their discoveries.)
Pluripotency factors
Several proteins have been identified that are capable of inducing or enhancing pluripotency in nonpluripotent (i.e., adult) cells. Of key importance are the transcription factors Oct-4 (octamer 4) and Sox-2 (sex-determining region Y box 2), which maintain stem cells in a primitive state. Other proteins that may be used to enhance pluripotency include Klf-4 (Kruppel-like factor 4), Nanog, and Glis1 (Glis family zinc finger 1).
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Pluripotency factors can be introduced into nonpluripotent cells in different ways, such as by plasmids or delivery as proteins or modified RNAs. Among the most effective and widely used methods, however, is delivery via a retroviral vector. Retroviral vectors can readily enter cells, making the genes they carry accessible to the cell; other retroviral activities are silenced. However, because retroviruses integrate into the nuclear genome, their use raises the risk of virus-induced tumour formation. Nonetheless, retroviral delivery remains highly effective, and technical advances to prevent the integration of retroviral material into the nuclear genome have allowed for the generation of iPS cells via ectopic expression (in the cytoplasm) of retrovirus-delivered transcription factors. Ectopic expression also has been achieved with the use of recombinant adeno-associated virus.
Research and therapeutic significance
Since the initial development of iPS cells, researchers have been working to improve the techniques and to learn what drives pluripotent stem cells to differentiate in particular ways. They also have been investigating the use of iPS cells in the treatment of certain diseases. Of significance is the potential to create patient-specific iPS cells (using a patient’s own adult cells), which could allow for the generation of perfectly matched cells and tissues for transplantation therapies. Such therapies could help overcome the risk of immune rejection, which is a major challenge in regenerative medicine.
Researchers also have used iPS cells to generate human blastoids, or three-dimensional blastocyst-like structures. The blastoids recapitulated many of the events of the first 10 days of human embryonic development, enabling researchers to investigate the span of human development immediately preceding implantation and providing new opportunities for understanding pregnancy and pregnancy loss.