'Adult' stem cells could skirt embryos' ethical dilemmas

In the emerging field of stem cell research, much of the promise -- and most of the controversy -- involves the breathtaking notion that replacement parts for our bodies one day may be grown from multipurpose cells derived from human embryos.

But scientists also are learning that embedded in our skin, flowing in our blood and stored in the deep reaches of our bones and brains are less versatile breeds of "adult" stem cells that may yet be coaxed into producing the same sort of medical advances without disturbing the ethical waters.

Because adult stem cells can be harvested without destroying a human embryo, they are the technology of choice among those, like President Bush, who have moral objections to research involving embryonic stem cells.

At a White House gathering last month, the president reaffirmed his opposition to such research but said his administration strongly supported the use of "alternative sources" of stem cells such as bone marrow and umbilical cord blood. "With the right policies and the right techniques, we can pursue scientific progress while still fulfilling our moral duties,'' he said.

Adult stem cells do not have the ability to turn into virtually any organ or tissue in the human body -- that is a trick reserved for their embryonic counterparts. Adult stem cells are also harder to study, because they do not renew themselves indefinitely in the lab, as embryonic stem cells do.

Despite those limits, new therapies using adult stem cells are likely to turn up in the clinic long before embryonic stem cells are tried. About 3,000 researchers are gathered in San Francisco for the third annual meeting of the International Society for Stem Cell Research, which ends today, and the majority of presentations on the program will deal with adult stem cells, ....

Here's the most hopeful information I've seen in awhile vis-a-vis the stem cell debate.

2005 June 08 Wednesday

Gene Activation Makes Adult Stem Cells Divide Rapidly

Adult stem cells are hard to grow. But MIT Whitehead Institute researchers have discovered that turning on a gene that is active in the early embryo causes adult stem cells to grow rapidly.

While research on human embryonic stem cells gets most of the press, scientists are also investigating the potential therapeutic uses of adult stem cells. Although less controversial, this research faces other difficulties. Adult stem cells are extremely difficult to isolate and multiply in the lab.

Now, as reported in the May 6 issue of Cell, researchers led by Rudolf Jaenisch of the Whitehead Institute have discovered a mechanism that might enable scientists to multiply adult stem cells quickly and efficiently.

"These findings provide us with a new way of looking at adult stem cells and for possibly exploiting their therapeutic potential," says Jaenisch, who also is a professor of biology at MIT.

I have repeatedly argued that it is just a matter of time before scientists find ways to turn adult stem cells into cells that can become any other cell type. This latest research from MIT is certainly a step in that direction. Note that these scientists used existing knowledge that the gene Oct4 is known to be active in embryonic stem cells. They turned that same gene on in adult stem cells. So this research is a clear step in the direction of making adult stem cells more like embryonic stem cells.

This research focuses on a gene called Oct4, a molecule that is known to be active in the early embryonic stage of an organism. Oct4's primary function is to keep an embryo in an immature state. It acts as a gatekeeper, preventing the cells in the embryo from differentiating into tissue-specific cells. While Oct4 is operating, all the cells in the embryo remain identical, but when Oct4 shuts off, the cells begin growing into, say, heart or liver tissue.

Konrad Hochedlinger, a postdoctoral researcher in Jaenisch's lab, was experimenting with the Oct4 gene, curious to see what would happen in laboratory mice when the gene was reactivated in adult tissue in which it had long been dormant. Hochedlinger found that when he switched the gene on, the mice immediately formed tumors in the gut and in the skin where the gene was active. When he switched the gene off, the tumors subsided, demonstrating that the process is reversible.

Discovering that simply flipping a single gene on and off had such an immediate effect on a tumor was unexpected, even though Oct4 is known to be active in certain forms of testicular and ovarian cancer. Still, the most provocative finding was that "Oct4 causes tumors by preventing adult stem cells in these tissues from differentiating," says Hochedlinger. In other words, with Oct4 active, the stem cells could replicate themselves indefinitely, but could not produce mature tissue.

One of the main obstacles with adult stem cell research is that,

This experiment showed that when Oct4 was reactivated, the adult stem cells in those tissues continued to replicate without forming mature tissue. In a mammal's body, this type of cell behavior causes tumors. But under the right laboratory conditions, it could be a powerful tool.

"This may allow you to expand adult stem cells for therapy," Hochedlinger said. "For instance, you could remove a person's skin tissue, put it in a dish, isolate the skin stem cells, then subject it to an environment that activates Oct4. This would cause the cells to multiply yet remain in their stem cell state. And because this process is reversible, after you have a critical mass of these cells, you can then place them back into the person where they would grow into healthy tissue."

"This could be very beneficial for burn victims," Jaenisch said.

The difference between adult and embryonic stem cells is just that they are in different regulatory states. Think of the genome of a cell as having a big set of switches on it with the pattern of which switches are set On and Off being one way in embryonic cells and other ways in other cell types. One reason I haven't been pessimistic about limitations on human embryonic stem research is that I expect scientists working with adult stem cells to find ways to change their regulatory state (i.e. their pattern of On and Off for their genetic switches) into the same states as is found in embryonic stem cells.

The irony of religious opposition to human embryonic stem cell research is that it logically leads scientists to look harder for ways to make adult stem cells act more like embryonic stem cells. The inevitable outcome of this search will be development of techniqes that convert adult stem cells into cells that can be turned into all other cell types - just as embryonic stem cells can. The ability of embryonic stem cells to turn into all other cell types is called pluripotency. Once non-embryonic stem cells can be made pluripotent then the religious opponents of human embryonic stem cell research are going to have to decide whether they believe all pluripotent stem cells are mini-humans or not.

Even if work with all human pluripotent stem cells is outlawed regardless of what cell type is converted into the pluripotent state or how it is turned into the pluripotent state that still won't stop scientists from manipulating adult stem cels into all other cell types. Such a ban would be just another regulatory barrier that could be programmed around with genetic engineering. Scientists could respond to that ban by fiding some difference between fully pluripotent cells and slightly differentiated cells and convert cells into slightly differentiated (i.e. slightly specialized) states rather into the fully pluripotent state.

So far the acrimonious debate about human embryonic stem cells has caused a big increase in adult stem cell funding by the US federal government (over $500 million per year in total stem cell research funding) and the passage of an initiative in California to spend $300 million per year on stem cells without a restriction on human embryonic funding. So obviously funding levels have risen greatly. The rate of advance is accelerating. But I'd like to see even greater acrimonious debate so that we can get total funding over $1 billion. Come on, get mad at each other. We need more funding!

By Randall Parker

http://www.family.org/cforum/fosi/bioethics/facts/a0035420.cfm

Tangible Therapies for Today

Acute Myloid Leukemia – Sixteen-year-old Nathan Salley is alive today, thanks to stem cells from umbilical cord blood. Nathan told a congressional subcommittee, "I am living proof that there are promising and useful alternatives to embryonic stem cell research. . . . Embryonic stem cell research did not save me – cord blood research did."2

Diabetes – Eleven out of 15 Type 1 diabetes patients are "completely off insulin" after receiving adult pancreatic cell transplants.3

Diabetes – Researchers at Harvard Medical School used animal adult stem cells to grow new islet cells to combat diabetes. Researcher Denise Faustman recalled, "It was astonishing! We had reversed the disease without the need for transplants." Plans for human trials are underway.4

Heart Disease – German heart specialist Bodo Eckehard Strauer successfully treated a heart patient using stem cells from the man's bone marrow: "Even patients with the most seriously damaged hearts can be treated with their own stem cells instead of waiting and hoping on a transplant," Dr. Strauer explained.5

Heart Disease - "Four out of five seriously sick Brazilian heart-failure patients no longer needed a heart transplant after being treated with their own stem cells." 6

Heart Disease - “Patients with heart failure experienced a marked improvement after being given injections of their own stem cells,” thanks to research at the University of Pittsburgh. 7

Heart Disease - Dr. Eduardo Marban, chief of cardiology at the Johns Hopkins School of Medicine, called the use of adult stem cells to treat failing hearts, “[t]he single most exciting development in cardiology in the last decade.” 8

Multiple Sclerosis (MS) – Thirty-six-year old Susan Stross is one of more than 20 MS patients whose conditions have remained steady or improved after receiving an adult stem cell transplant. The same results are reported with several hundred patients worldwide.9

Multiple Sclerosis (MS) - Research conducted by Dr. Mark Freedman at the University of Ottawa suggests that most of the 32 MS patients in the trial “experienced clinical stabilization or improvement of symptoms.” 10

Non-Hodgkin's Lymphoma – Forty-year-old Mark Fulford was not a match for a conventional bone marrow transplant, so doctors turned to stem cells found in umbilical cord blood. "There are people alive now who wouldn't have been without this, and I'm living proof."11

Paralysis/Spinal Cord Injury - After sustaining paralyzing spinal cord injuries, Susan Fajt, Laura Dominguez and Erica Nader of the U.S. are each regaining muscle control and walking with the aid of braces due to stem-cell transplants from their own nasal cavities conducted in Portugal. Six paralyzed Russian patients are also walking thanks to a similar therapy. 12

Paralysis/Spinal Cord Injury - Maria da Graca Pomeceno of Brazil regained her ability to walk and talk after a bone marrow stem-cell transplant from her pelvis. 13

Paralysis/Spinal Cord Injury - Treatment using stem cells derived from umbilical cord blood allow Hwang Mi-Soon of South Korean to walk again with the aid of a walker. “This is already a miracle for me,” says Mi-Soon. 14

Parkinson’s Disease - A California man with Parkinson's disease experienced more than an 80 percent reduction in his symptoms after he received an injection of his own neuronal (brain) stem cells. Dennis Turner says before the treatment, “I couldn’t put my contact lenses in without a big problem. Now it’s not problem.” 15

Sickle Cell Anemia – In his struggle against sickle cell anemia, seventeen-year old Keone Penn experienced suicidal thoughts before an umbilical cord blood transplant cured him of the disease. Today, Penn says, “Sickle cell is now part of my past…Cord blood saved my life.” 16

Stroke - Catholic University of Korea researchers report “great improvement in the paralysis symptoms and speech disorders” in three of five stroke patients who received transplants with their own bone marrow stem cells. 17

Stroke - Brazilian doctors will test a similar treatment on 15 patients after encouraging results with one stroke patient. 18

Promise for Tomorrow

Reports of "Master Stem Cell" discoveries –
"A stem cell has been found in adults that can turn into every single tissue in the body. It might turn out to be the most important cell ever discovered."19

Researchers at New York University School of Medicine announced, "There is a cell in the bone marrow that can serve as the stem cell for most, if not all, of the organs in the body. . . . This study provides the strongest evidence yet that the adult body harbors stem cells that are as flexible as embryonic stem cells."20

McGill University researchers discover "stem cells deep in the skin of rats and humans that can become fat, muscle or even brain cells. . . . Scientists are driven by the hope of bringing science closer to treatments for spinal cord injuries, juvenile diabetes, heart disease and brain disorders — treatments made from patients' own cells."21

These are stem cells from adult bone marrow that do not trigger rejection, "even after the cells differentiate into specialized tissues such as bone or fat." The "cells seem to go only to damaged areas . . . (turning) into heart muscle, blood vessels, and fibrous tissue." 22

1National Marrow Donor Program, "Diseases Treatable by Stem Cell Transplant," National Marrow Donor Program
2"Teenager testifies he's ‘living proof' of stem-cell option, Denver Post, July 22, 2001.
3 "Cell grafts lend freedom to diabetics," Medical Post, June 19, 2001.
4"Adult stem cells effect a cure," Harvard University Gazette, July 19, 2001.
5"Stem cell therapy repairs a heart," Daily Telegraph (London), Aug. 25, 2001.
6"Stem cells used to repair heart tissue," MSNBC News, accessed on September 8, 2003 at http://www.msnbc.com/news/959999.asp
7 “Stem cell therapy improves heart failure,” Reuters, January 25, 2005.
8“Scientists try to heal heart with stem cells,” Baltimoresun.com, December 13, 2004.
9"High on the future: Already saving lives, stem cell research may soon be in full swing," Seattle Times, Aug. 20, 2001.
10 “Mixed news on bone marrow transplant,” Paraplegia News, June 1, 2003.
11"Different kind of stem cell already saving lives," (Denver) Rocky Mountain News, August 18, 2001.
12 “Texas stem cell recipients revive debate,” Austin American-Statesman, July 15, 2004; “Paraplegic improving after stem-cell implant,” Indianapolis Star, January 16, 2005; “Doctors in Russia prove stem cells can be used in treating spine injuries, RIA Novosti, December 6, 2004.
13 “Stem cell treatment allows paralyzed Brazilian to walk, talk again,” Agence France Presse, November 19, 2004.
14 “Umbilical cord cells allow paralyzed woman to walk, Daily Telegraph (London), November 30, 2004.
15 “Stem cell transplant works in California case,” Washington Post, April 9, 2002.
16"A voice of hope rings out in Senate,” Atlanta Journal-Constitution, June 13, 2003.
17“Stem cell implant effective in treating cerebral infarction,” The Korea Times, December 9, 2004.
18 “Cells used in stroke work,” Ottawa Sun, November 20, 2004.
19"Ultimate stem cell discovered," NewScientist.com, Jan. 23, 2002.
20"Researchers discover the ultimate adult stem cell," Science Daily Magazine, May 4, 2001.
21"Stem cell research matures in Montreal studies," Los Angeles Times, Aug. 19, 2001.
22"No matter who you are, your body won't reject this universal healer," New Scientist, Dec. 15, 2001.

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