Stem Cell Innovations Produces Human Pluripotent Stem Cells; Cells Eligible for Use in Government Funded Laboratories

This looks interesting.

Stem Cell Innovations Produces Human Pluripotent Stem Cells; Cells Eligible for Use in Government Funded Laboratories
3/29/2006 6:41:00 AM EST

Dr. James H. Kelly, Chief Executive Officer of Stem Cell Innovations, Inc. (OTCBB: SCLL), will present data today at the Keystone Symposium on Stem Cells in Vancouver demonstrating that the Company has produced multiple lines of human pluripotent stem cells. Because these cells are derived from fetal tissue, not early embryos, they are eligible for use in laboratories funded by the National Institutes of Health.

Stem cells are cells that can produce additional stem cells as well as one or more other types of cells. Pluripotent stem cells can develop into most, if not all, of the tissues of the organism. To date, two types of mammalian stem cells have been shown to be truly pluripotent: the well-known embryonic stem cells (ES cells), which are cultured from very early embryos and are patented by the University of Wisconsin, and the lesser-known embryonic germ cells (EG cells), which are developed from fetal gonadal tissue. EG cells were originally developed by Dr. Brigid Hogan and have been patented and licensed exclusively to Amphioxus Cell Technologies, Inc., a wholly owned subsidiary of the Company, but have been used in only a few laboratories because of the difficult nature of their isolation and growth. While the widespread use of ES cells has been hampered by ethical issues and government funding limitations, Congressional legislation treats fetal tissue differently. The U.S. Department of Health and Human Services has stated that research involving the derivation and use of EG cells may be conducted with Federal support (http://www.hhs.gov/ohrp/humansubjects/guidance/stemcell.pdf).

In his presentation at the Symposium, Dr. Kelly will present data demonstrating that Company scientists were able to overcome many of the problems inherent in the production of EG cells. First, the Company's cell lines are able to maintain their undifferentiated state and normal chromosome complement. Second, the Company is able to produce its cell lines without feeder layers (layers of foreign cells used as an environment to grow the stem cells which can complicate the process and result in contamination of the stem cells). Finally, the Company is able to efficiently develop multiple lines, the first step in creating banks of cells that can be matched to patients in cell therapies.

Hematopoietic Stem Cells Fail to Transdifferentiate into Neurons

Ouch!

Researchers in Sweden have a paper out in Stem Cells that tries (keyword: tries) to put the kibosh on the transdifferentiation hopes. They took purified hematopoietic (blood-forming) stem cells and cultured them in neural differentiation medium.

Culturing embryonic stem cells in said medium causes them to develop toward a neural fate, so these researchers were checking to see if the same culturing medium would cause adult stem cells to transform into a neural type. Unsurprisingly, this doesn't work. But it's not all that bad.

Truly.

Previous studies that have shown transdifferentiation failed to use pure populations of hematopoietic stem cells, meaning they were "contaminated" by a variety of non-hematopoietic stem cells. There is a very strong possibility that these "contaminating" cells contributed to the observed transdifferentiation.

The reason? In newts, regeneration occurs naturally. Slice off their leg, they'll grow a new one. Really, really cool stuff. If humans could do this, it would be even cooler. But they can't.

Or can they?

Regeneration in newts is made possible by their native satellite cell population. Humans have a similar population of cells that help regenerate damaged skeletal muscle tissue. If it's damaged, the satellite cells move into action. These satellite cells also contribute to wound healing.

Regeneration in humans is, therefore, possible. It is limited, however, by its environment. By correctly manipulating the environment (to allow for transdifferentiation or redifferentiation), it is very likely that the regenerative abilities of humans can be enhanced to promote complete limb regeneration. Amputees would no longer be forced to rely on prosthetic limbs.

Transdifferentiation probably is not directly possible in humans, but if coaxed along through the proper series of steps, it can (or should) be possible. (If transdifferentiation occurs through a series of steps, I believe it's more commonly referred to as redifferentiation, but it's the same thing.)

This is cool stuff. Let me tell you.

Nuclear Reprogramming

Gee, you wait a few hours and someone beats you to the punch.

Rebecca over at Mary Meets Dolly blogged about a Technology Review article out today entitled Nuclear Reprogramming. She knows her stuff, so give her a read and then come back.

Allrighty then. So you now have some idea about what's being proposed. Essentially, deriving embryonic stem cells without creating or destroying an embryo. The Holy Grail, if you will.

All these weird terms are thrown out at you -- Cdx2, Nanog, ANT, PGD -- and I plan on skipping those today. Because, really, they're just clutter.

Today, we're going to discuss cell biology and, hopefully, we're going to do so in a way that a fifth grader can understand. So, please, forget everything you know about a cell for the duration of this entry. When you're done, you'll thank me.

Biology Made Easy

If you ask someone what a cell is, you'll get different answers from different people.

Gaming enthusiasts will delight you with tales of the new processor powering the PlayStation 3. Stephen King fans will reminisce of the bars that could not contain Andy Dufresne in The Shawshank Redemption. Those who have sat through a biology class will tell you that a cell is the basic unit of life.

They would all be right. I'm going to offer you a different definition.

A cell is a component of life that contains a nucleus and cytoplasm, and organelles that help it function. A cell's functioned is defined primarily by two things: the genes expressed in its nucleus, and the proteins floating around in the cell.

Lower estimates put the number of genes in the human body right around 25,000. This makes the number of unique genetic expression profiles almost impossible to consider. It gets even more complicated, but we're going to keep things simple and say that there are only 4 genes -- A, B, C, and D.

Each of these genes can be expressed -- turned on -- or not -- turned off -- giving us 16 distinct genetic profiles. (A, AB, ABC, ABCD, ABD, AC, ACD, AD, B, BC, BCD, BD, C, CD, D, [none])

Each of these profiles will cause the cell to perform a different function. AB, as an example, would function as a zygote; ABC an embryonic stem cell; ACD a neural stem cell; AD a neuron; and so on and so forth.

I hope you're still with me, because here's the cool part -- scientists can add and delete genes in the laboratory. Say CD is a skin cell. By adding the A gene, the cell would become a neural stem cell. By deleting C from this neural stem cell, the cell becomes a neuron.

More interestingly, scientists could take a skin cell (CD), delete the D, add an A and a B and -- bingo! -- an embryonic stem cell (ABC). All without creating an embryo.

That's the power of nuclear reprogramming. This is the future of science.

This is the stuff that makes me drool.

Why Must Though Forsake Me, Bloomberg?

Bloomberg has a semi-decent piece up describing the current state of embryonic stem cell bills in Congress. If you have been following the issue, you may be able to understand what they're saying. If you haven't, good luck.

But that's why I'm here, to clarify these issues in my normal cheerful way. Let's begin.

Bush has prohibited federal funding for any research using material from newly created human embryos since 2001. While Frist has promised to bring a measure before the Senate to overturn Bush's ban, a plan to begin debate this month has been stalled.

Scientists inject embryonic cells with genetic material, creating regenerative tissue that in theory could be implanted in patients to cure diseases from Parkinson's to juvenile diabetes. The Republican Party's evangelical Christian base is opposed to the research because human embryos are destroyed in the process.

There's a subtle segway here that isn't explicitly clear.

The first paragraph accurately describes Bush's 2001 ban on federal funding for embryonic stem cells, but it is incomplete. Bush's ban only relates to ESCs derived in a manner in which an embryo is destroyed. One proven "alternative" method to obtain embryonic stem cells comes from Kevin Eggan. In 2005, he fused an adult cell with an ESC, which produced a "cloned" ESC -- all without creating or destroying an embryo. Research using these ESCs would be eligible for federal funding.

Now the segway, and the inaccuracies. Bloomberg reports that the Evangelical Christian base opposes this method. In actuality, they do not. Those who are against expanding Bush's restrictions oppose it because they are against detroying embryos.

The procedure Bloomberg describes does not rely on the destruction of embryos, so I have to think they meant transferring an adult nucleus into an enucleated egg, in which case an embryo is created. Evangelicals do, largely, oppose this.

The article goes on to discuss the political maneuverings of various Senators about this issue. Sam Brownback (R-KS) wants a week long discussion on bioethics where opponents can introduce legislation to block expansion of the research, and he thinks he has the 51 votes necessary to do so. Tom Harkin (D-IA) thinks, when push comes to shove, a number of fence-sitting Republicans will vote in favor of expansion.

Senator Frist (R-TN), staying consistent with his previous statements, said he would like to consider "a range of bills and amendments" when the Stem Cell Research Enhancement Act comes to the floor for a vote. I am (no surprise) hoping the Respect for Life Pluripotent Stem Cell Act is one of those bills.

LifeNews Exploiting Dana Reeve's Death

Tim Quayle, writing for LifeNews.com, mourns the fact that the mainstream media (allegedly) omitted the fact that Dana Reeve supported stem cell research.

The national media was full of broken hearts last week when Dana Reeve died at 44, after nearly a decade of caring for disabled “Superman” star Christopher Reeve. It was obvious from the coverage that this woman had won hearts and made friendships in the media elite. But something strange happened in all the laudatory waves of coverage. Someone shrunk her activism.

It’s common for reporting on embryo-destroying stem cell research to leave out the embryo-destroying part. But the tear-stained accounts of Reeve’s sudden end often left out the words “stem cell” as well.

My guess is this guy doesn't consult Google. From a post I made elsewhere last Saturday:

Google News currently returns 1690 results for dana-reeve.

201 results reference her support of stem cell research.

Only 3 results reference her work toward passing the Christopher Reeve Paralysis Act.

Stem Cells - mentioned once in every (approximately) 8.5 stories.

CRPA - mentioned once in every (approximately) 563 stories.

Tim Quayle appears saddened that the media outlets he sampled placed her support for a cure for paralysis over her support for ESC research, but he goes on to use her death to promote his agenda. No matter what you think of someone's opinions, it is rather tacky, and uncool, to use their death to lecture people.

Tim, learn some tact. In my opinion, your spiel does harm to the Pro-Life community. Those who carefully picked over her words to push their agenda, intentionally omitting facts that don't fit their preconceived perceptions, do the same to their respective agendas.

To the best of my knowledge, Dana Reeve's primary focus was on improving the Quality of Life of people until the day a cure arrives. Not stem cells, and not a cure for paralysis -- although they were an important focus.

She wanted people to live with a decent Quality of Life -- and that's something everyone should respect.

Therapeutic Regeneration?

PhD or not, this guy's obviously tapped the crack pipe a time or two too many. His terms are all wrong.

In attempting to redefine therapeutic cloning ("therapeutic regeneration"), he equates SCNT with deriving cells from IVF embryos.

Uh, no.

For therapeutic regeneration, these cells can be derived from the ample numbers of embryos that will otherwise be discarded by in-vitro fertilization clinics across the nation.

He claims that generic bans on cloning in certain states forbid derivation of embryonic stem cells from to-be-discarded IVF embryos, which is clearly untrue.

Although a few states (California, Massachusetts, New Jersey, and Ohio) have authorized therapeutic regeneration research using stem cells, many more states (including Missouri, Arkansas, Indiana, Iowa, North Dakota, South Dakota, and Michigan) have passed severely restrictive statutes that prohibit "cloning" research, without making the critically important distinction between reproductive and therapeutic purposes. As a result, research that uses embryos to establish stem cell lines is prohibited, even though these embryos are obtained with the express consent of the donors, and if not used are otherwise destined to be discarded.

Cloning bans prohibit cloning. Derivation of embryonic stem cell lines does not require cloning, so these prohibitions in no way prohibit ESC line derivation. Other laws may, but it is not the ones who ban cloning.

I think this would totally blow up in proponent's faces if they tried to use it. Instead of making things easier, propagating this blatant disinformation would make things much more difficult.

Frightening.

South Korea Revokes Hwang's Stem Cell License

SEOUL, March 16 (Reuters) - South Korea revoked the research licence of disgraced stem cell scientist Hwang Woo-suk on Thursday, saying he had not published a credible paper on the subject within the allotted time frame to deserve one.

I wish I could say I feel sorry for him.

Welcome Readers of Wired News!

I would like to extend a warm welcome to all readers visiting from Wired News. My blog is a little hectic right now with respect to comments, as they were disabled for a while. From now on, they will be turned on.

Thank you for visiting, and feel free to contact me at se-wired@comcast.net if you have any comments. :)

Dana Reeve Dies

SHORT HILLS, N.J. -- Actress Dana Reeve, who fought for better treatments and possible cures for paralysis through the Christopher Reeve Foundation, named for her late actor-husband, has died. The Associated Press reports that she was 44, while CNN reports she was 45.

Reeve died late Monday at Memorial Sloan-Kettering Medical Center of lung cancer, said Sean Dougherty, a spokesman for the foundation. Survivors include a teenage son, Will, and two stepchildren, Matthew and Alexandra.

"On behalf of the entire board of directors and staff of the Christopher Reeve Foundation, we are extremely saddened by the death of Dana Reeve, whose grace and courage under the most difficult of circumstances was a source of comfort and inspiration to all of us," Kathy Lewis, president and CEO of the foundation, said in a statement.

Reeve had announced on Aug. 9 that she had lung cancer.

Christopher Reeve, the one-time Hollywood "Superman" turned activist for spinal cord research after a horse-riding accident, died Oct. 10, 2004.

Dana Reeve was a constant companion and supporter of her husband during his long ordeal and his work for a cure for spinal cord injuries.

She was chairwoman of the Christopher Reeve Paralysis Foundation, which funds research on paralysis and works to improve the life of the disabled. To date, it has awarded $55 million in research grants and $7.5 million in quality of life grants.

She was performing in the Broadway-bound play "Brooklyn Boy" in California when she had to streak home to reach her husband's bedside before he died. She gave up the role for the New York run.

Reeve also served on the boards of The Williamstown Theatre Festival, The Shakespeare Theatre of New Jersey, TechHealth, and The Reeve-Irvine Center for Spinal Cord Research and as an advisory board member to the National Family Caregivers Association.

She received numerous awards for her work, including the Shining Example Award from Proctor & Gamble in 1998, an American Image Award from the AAFA in 2003. In 2005, the American Cancer Society named her Mother of the Year.

She is also survived by her father, Dr. Charles Morosini, and sisters Deborah Morosini and Adrienne Morosini Heilman.

It's too sad for words.

At this time, no plans for a funeral have been announced. For those who care to do so, donations may be made in Dana's memory to the Christopher Reeve Foundation, 636 Morris Turnpike, Short Hills, New Jersey 07078 or online at www.ChristopherReeve.org

Altered Nuclear Transfer - Not So Ethical?

Altered Nuclear Transfer (ANT) is one of the procedures Congressman Roscoe Bartlett spoke of when addressing methods of funding research into "ethical methods of deriving embryonic stem cells." But, for those who oppose SCNT, is it really ethical?

Let's take a closer look.

ANT describes a general concept for performing an altered form of somatic cell nuclear transfer (SCNT); thus the name. As we know, SCNT involves replacing the nucleus of an egg cell with one from an adult cell and stimulating it with electricity, tricking the cell into believing it is fertilized.

The NT-product, or clone, then attempts to do ... something. Essentially, whatever the instructions in the cytoplasm tell it to do. Scientists hope that they can use SCNT to make a cell that functions as a zygote, developing into a morula and eventually a blastocyst. It is at this point that scientists will attempt to extract the embryonic stem cells, destroying the blastocyst in the process.

ANT is SCNT, with a small difference: a modification is made to either the egg's cytoplasm or the donor cell's nucleus to prevent an embryo from developing. (Some would say, ANT is SCNT with the aim of creating a "developmentally disabled" embryo. The difference in terminology is philisophical, so please choose the definition you prefer and continue. I am not saying which is right or wrong.)

The most prominent proponent of ANT is Stanford Bioethicist William Hurlbut. The best known proposed implementation of ANT is through silencing the expression of a gene known as Cdx2. In mice, this gene contributes to the formation of the trophectoderm, or outer "shell" of the blastocyst. Silencing this gene does not interfere with the formation of the blastocyst's inner cell mass (ICM), which is what scientists extract to obtain embryonic stem cells.

So far, this all sounds like it could be pretty kosher. If you prevent the formation of the trophectoderm, you interfere with the integrity of the embryo. If you disrupt the embryo's integrity, it's not really an embryo. Right?

Well, the trophectoderm later forms the placenta. The placenta, of course, is necessary for the embryo to implant into the uterus. The placenta is, effectively, the feeding tube that allows nutrients and oxygen to pass from the mother to the embryo (and later to the fetus). Silencing Cdx2, basically, starves the embryo of the nourishment it needs to further develop into a fetus.

If a person believes a zygote is a life, I see no reason why they should support this method.

Fortunately, the vast majority of those who support this method only support it conditionally. They specify that they only support such research in animal models, in an attempt to see if it works.

Interestingly, William Hurlburt himself does not believe that silencing Cdx2 is necessarily the "holy grail". Writing in Wired, Clive Thompson reported:

For his part, Hurlbut is particularly incensed that his detractors keep oversimplifying his proposal. They maintain that the experiment on mice - knocking out CDX2 - wouldn't work in humans. Hurlbut insists he's never claimed it would. He says he cited CDX2 only as an example of what's possible; in humans, he suspects, you'd need to knock out some other gene, and only experiments will figure out which one.

This paragraph, particularly the last sentence, should raise major concerns for Catholics. In order to validate the technique in humans, experimentation on embryos would be required. Pope Benedict XVI recently indicated that such research should never be performed (the understood exception being that it can be conducted if the aim of the research is to save the life of the embryo), which throws up a significant hurdle.

Now, all this doesn't mean ANT is a bad idea. One implementation of ANT could propose to alter the egg's cytoplasm so that it directly reprograms the donor nucleus so that the cell becomes an embryonic stem cell.

This version would still face one ethical drawback: it would still rely on women to donate their eggs. Could women be pressured to undergo ovarian hyperstimulation to donate eggs? You bet. Would they? In some instances, it's hard to say they wouldn't be.

Is forcing women to donate eggs really that big of a deal, when the potential benefits are so great? Aside from the potential side effects, I guess it's a personal decision. Personally? I say it is.

Well, I guess that's it for tonight. Thanks for reading!

Recent Congressional Action

Not much stem cell related discussion has transpired in Congress so far this year, but pro-life Congressman Roscoe G. Bartlett (R-MD) gave an okay speech on alternative methods of obtaining embryonic stem cells for research. I say it was only "okay" because it was given during a night of speeches, with no discussion following the speech. Without discussion, nothing is usually learned.

I will have more to say on the actual content of his speech later on, but I just wanted to point it out for now to my lovely readers. Some of the ideas he proposed were crap (altered nuclear transfer; deriving stem cells from organismically dead embryos; single blastomere approach), while others were great (dedifferentiation).

I'm not biased or anything. <g>

On another note, Senator Bob Menendez (D-NJ) recently signed on as a cosponsor to the Stem Cell Research Enhancement Act (SCREA). Menendez was selected by outgoing Senator John Corzine (elected as Governor of New Jersey) as his replacement, so this does not come as a surprise.

His support of the SCREA means the Senate is only 25 (confirmed) votes shy of overriding a Presidential Veto. The House of Representatives, by comparison, is still over 80 (confirmed) votes away from this goal.