Cell respecialization

[Steven Edwards]

Good Dr,

If I recall correctly, cells can respecialize? Correct?

Say you take a small batch of skin cells, mark them, then stick them into a large culture of... why not, nerve cells? Would they eventually begin functioning as nerve cells?

-Steven

[SCI-Nurse]

You may want to post this over on the Cure Forum, which is moderated by Dr. Young. He does not always get the time to check out all the posts on the other forums. (KLD)

[Wise Young]

I just moved your topic from the Life Forum to the Cure Forum where it would be more appropriate and people who would be interested in the answer would be more likely to see it.

There is controversy amongst scientists whether dedifferentiation can occur, i.e. whether a differentiated cell such as a skin or liver cell can regress back to a stem cell and produce other kinds of cells. Some data suggest that it can happen. For example, several groups (Mezey, Brazleton, Black, and others) have now shown that bone marrow stem cells can produce neurons. This was regarded by many scientists as a major breakthrough because bone marrow cells belong to a completely separate lineage of cells, i.e. mesenchymal as opposed to epithelial.

On the other hand, there are some who believe that bone marrow contains unspecialized stem cells that can produce all kinds of cells and that the finding does not mean that bone marrow precursor cells can dedifferentiate into neural precursor cells.

A still unanswered question is where stem cells come from. We know that the egg produces stem cells. There is beginning to be a trend to redefine a stem cell. As you know, a stem cell is currently defined as a pluripotent cell (i.e. a cell that can produce different kinds of cells). There is no differentiation between a stem cell and a progenitor cell, both of which can produce many different kinds of cells. The word stem cell is usually reserved for those cells that do not have restricted lineages but the definition was unclear.

I personally think that the word stem cell should be reserved only for those cells that can produce other stem cells. There is no question that embryonic stem cells are truly stem cells if one used this definition whereas it is not clear that all adult "stem cells" can produce other stem cells.

In class, yesterday, we discussed at some length the difference between adult and embryonic stem cells. Usually three differences have been mentioned:

1. Embryonic stem cells are capable of more divisions (as many as 300) than adult stem cells (probably 30-50 divisions).

2. Embryonic stem cells are more pluripotent, they produce more types of cells than adult stem cells.

3. Embryonic stem cells are more robust than adult stem cells, i.e. they survive better and longer when placed in culture or transplanted.

It is important to note that we currently do not have sufficient experience with adult stem cells to say with certainty that they do not live as long as embryonic stem cells, that they are less pluripotent, and that they are less robust. However, it is true that adult tissues have fewer stem cells than embryonic, fetal, or even neonatal tissues. For this reason, it is much more difficult to harvest adult stem cells than embryonic stem cells.

Available data, however, strongly support the existence of pluripotent adult stem cells in animals and in humans. They are true stem cells because adult stem cells will produce other stem cells. I also believe that as we develop better technology for harvesting and culturing adult stem cells, we will find that they can survive and continue to divide for a long time in cultures and after transplantation.

Wise.

[Steven Edwards]

Dr. Young,

I searched PubMed for enucleated-adult, enucleated-somatic, enucleated-neural, enucleated-fibroblast, and enucleated-neuron with no luck. Are you aware of any nuclear transfer studies where the "recipient" enucleated cell is an adult stem- or non-stem-cell?

Proliferation and/or renewal rates would probably be low, but it would be interesting (to me, at least) to test if somatic cells could be reprogrammed directly into other somatic cells or if an ESC nucleus transplanted into an enucleated non-ESC cell would force some level of dedifferentiation.

Thanks in advance... take your time answering.

[Leo]

Hi Steven, I think this company has made the claim to be able to do what your talking about. http://www.nucleotech.com/index.html

I hope Wise will have the time and opportunity to meet with Dr. Collas from Norway when he goes there this fall.

We have some researchers here in South Dakota who did some traing under Collas. Pretty exciting.

[Steven Edwards]

Thanks for the link, Leo. That's a good example of what I was referring to. I wouldn't mind finding out about the efficacy of converting fibroblasts into neural cells referenced in their last press release.

[Wise Young]

Steven, I was just looking at the dates of these posts. Wow, it must have been one of the earliest posts that you made on CareCure, on August 10, 2001 (about 2 weeks after the site started).

I think that I posted over two years ago about the efforts in Singapore to fuse embryonic stem cells and umbilical cord blood cells. Fusion is of course a form of nuclear transfer. Kevin Egan at Harvard is working of fusing human embryonic stem cells with fibroblasts. Markus Grompus in Oregon is working on inserting stem cell genes such as Nanog into cells to see if this would make them become more like stem cells. Of course, there is all that excitement about making oocytes from bone marrow or fetal skin cells. Note that these "oocyte-like" cells are diploid (i.e. has two sets of chromosomes) and, if they develop any further, may well yield cells that behave like embryonic stem cells. So, there are people who are working on the problem.

Wise.

[Steven Edwards]

The posts are quite old. I was browsing the early posts to try and get a feel for the community immediately before and after President Bush's restrictions.

I am familiar with (and hopeful for) Grompe's work. The fusion work, I'm not so familiar with. I was hoping that somebody may have attempted nuclear transfer from one somatic cell to another in an attempt to reprogram the recipient cell.

Regarding fusion, the resulting cells being tetraploid would likely lead to the need for animal studies to see whether or not fused tetraploid cells act properly when transplanted and do not become tumorgenic. While the science is interesting and should be carried out, I would prefer an approach with fewer potential delays in getting a cure into trials.

Maybe my upcoming anniversary is making me paranoid of potential trial delays. Who knows? Either way, I would rather have a diploid cell (NT product) transplanted into me because I think it is both a quicker route to trials and safer.

[bigbob]

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Pitt scientists hope to take sting out of stem cell fight

By Jennifer Bails
TRIBUNE-REVIEW
Friday, August 5, 2005

University of Pittsburgh researchers have discovered what could be the ultimate prize in biomedicine -- cells that behave like embryonic stem cells but don't raise confounding ethical questions.

These cells -- called amniotic epithelial cells -- share many of the characteristics that make embryonic stem cells so highly coveted, such as the capacity to become cells for other body tissues and organs and to make copies of themselves, according to Stephen Strom, an associate professor of cellular and molecular pathology at Pitt.

Unlike embryonic stem cells, their harvest doesn't require the destruction of human embryos.

Amniotic epithelial cells can be collected after full-term childbirth from the placenta's amnion, a thin cavity filled with fluid that forms eight days after fertilization to cushion the fetus, Strom said.

This means placentas usually dumped in the trash as medical waste could represent a nearly limitless source of "stem cell-like" cells for treating conditions such as liver and heart disease and diabetes, said Strom, who serves on the faculty of the university's McGowan Institute of Regenerative Medicine.

"If one could take something that is normally thrown away and use it for regenerative medicine, that's the ultimate in recycling," Strom said. "We're stupid people who may have been throwing out the baby -- this tremendous source of stem cells -- with the bath water for years and years."

More than 4 million live births occur in America each year, according to U.S. Census figures. For each placenta, the researchers calculate there are about 300 million amniotic epithelial cells that easily could be multiplied to 10 billion and 60 billion cells.

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