Pluripotent Stem Cells 101 Boston Children’s Hospital

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Pluripotent stem cells are master cells. Theyre able to make cells from all three basic body layers, so they can potentially produce any cell or tissue the body needs to repair itself. This master property is called pluripotency. Like all stem cells, pluripotent stem cells are also able to self-renew, meaning they can perpetually create more copies of themselves.

There are several types of pluripotent stem cells, including embryonic stem cells. At Childrens Hospital Boston, we use the broader term because pluripotent stem cells can come from different sources, and each method creates a cell with slightly different properties.

But all of them are able to differentiate, or mature, into the three primary groups of cells that form a human being:

Right now, its not clear which type or types of pluripotent stem cells will ultimately be used to create cells for treatment, but all of them are valuable for research purposes, and each type has unique lessons to teach scientists. Scientists are just beginning to understand the subtle differences between the different kinds of pluripotent stem cells, and studying all of them offers the greatest chance of success in using them to help patients.

Types of pluripotent stem cells:

All four types of pluripotent stem cells are being actively studied at Childrens.

Induced pluripotent cells (iPS cells):Scientists have discovered ways to take an ordinary cell, such as a skin cell, and reprogram it by introducing several genes that convert it into a pluripotent cell. These genetically reprogrammed cells are known as induced pluripotent cells, or iPS cells. The Stem Cell Program at Childrens Hospital Boston was one of the first three labs to do this in human cells, an accomplishment cited as the Breakthrough of the Year in 2008 by the journal Science.

iPS cells offer great therapeutic potential. Because they come from a patients own cells, they are genetically matched to that patient, so they can eliminate tissue matching and tissue rejection problems that currently hinder successful cell and tissue transplantation. iPS cells are also a valuable research tool for understanding how different diseases develop.

Because iPS cells are derived from skin or other body cells, some people feel that genetic reprogramming is more ethical than deriving embryonic stem cells from embryos or eggs. However, this process must be carefully controlled and tested for safety before its used to create treatments. In animal studies, some of the genes and the viruses used to introduce them have been observed to cause cancer. More research is also needed to make the process of creating iPS cells more efficient.

iPS cells are of great interest at Childrens, and the lab of George Q. Daley, MD, PhD, Director of Stem Cell Transplantation Program, reported creating 10 disease-specific iPS lines, the start of a growing repository of iPS cell lines.

Embryonic stem cells:Scientists use embryonic stem cell as a general term for pluripotent stem cells that are made using embryos or eggs, rather than for cells genetically reprogrammed from the body. There are several types of embryonic stem cells:

1. True embryonic stem cell (ES cells)These are perhaps the best-known type of pluripotent stem cell, made from unused embryos that are donated by couples who have undergone in vitro fertilization (IVF). The IVF process, in which the egg and sperm are brought together in a lab dish, frequently generates more embryos than a couple needs to achieve a pregnancy.

These unused embryos are sometimes frozen for future use, sometimes made available to other couples undergoing fertility treatment, and sometimes simply discarded, but some couples choose to donate them to science. For details on how theyre turned into stem cells, visit our page How do we get pluripotent stem cells?

Pluripotent stem cells made from embryos are generic and arent genetically matched to a particular patient, so are unlikely to be used to create cells for treatment. Instead, they are used to advance our knowledge of how stem cells behave and differentiate.

2. Stem cells made by somatic cell nuclear transfer (ntES cells)The term somatic cell nuclear transfer (SCNT) means, literally, transferring the nucleus (which contains all of a cells genetic instructions) from a somatic cellany cell of the bodyto another cell, in this case an egg cell. This type of pluripotent stem cell, sometimes called an ntES cell, has only been made successfully in lower animals. To make ntES cells in human patients, an egg donor would be needed, as well as a cell from the patient (typically a skin cell).

The process of transferring a different nucleus into the egg reprograms it to a pluripotent state, reactivating the full set of genes for making all the tissues of the body. The egg is then allowed to develop in the lab for several days, and pluripotent stem cells are derived from it. (Read more in How do we get pluripotent stem cells?)

Like iPS cells, ntES cells match the patient genetically. If created successfully in humans, and if proven safe, ntES cells could completely eliminate tissue matching and tissue rejection problems. For this reason, they are actively being researched at Childrens.

3. Stem cells from unfertilized eggs (parthenogenetic embryonic stem cells)Through chemical treatments, unfertilized eggs can be tricked into developing into embryos without being fertilized by sperm, a process called parthenogenesis. The embryos are allowed to develop in the lab for several days, and then pluripotent stem cells can be derived from them (for more, see How do we get pluripotent stem cells?)

If this technique is proven safe, a woman might be able to donate her own eggs to create pluripotent stem cells matching her genetically that in turn could be used to make cells that wouldnt be rejected by her immune system.

Through careful genetic typing, it might also be possible to use pES cells to create treatments for patients beyond the egg donor herself, by creating master banks of cells matched to different tissue types. In 2006, working with mice, Childrens researchers were the first to demonstrate the potential feasibility of this approach. (For details, see Turning pluripotent stem cells into treatment).

Because pES cells can be made more easily and more efficiently than ntES cells, they could potentially be ready for clinical use sooner. However, more needs to be known about their safety. Concerns have been raised that tissues derived from them might not function normally.

Read more about pluripotent stem cells by following these links:

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Pluripotent Stem Cells 101 Boston Children's Hospital

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