SCIENCE
Revisiting Stem Cells
By Dr. Rizwana Rahim
Chicago, IL

Stem cell research had an important anniversary last week (9 August). Not as much of any specific advance in research as of the restrictions placed on it.
Perhaps the best way to update my article on ‘Stem Cells: Science and Ethics’ that appeared little over a year ago in the Pakistan Link (24 June 2005, http://www.pakistanlink.com/Commentary/2005/Jun05/24/02.HTM ) would be to say: The politics still drives the science in this area, while the science – enormously complicated, to begin with – has much unrealized potential for cell therapy.
Stem cells are unlike any other kinds of cells in the body: they are unspecialized cells, which are capable of dividing for long without any change, but they can become or grow into any cell in any organ (about 200 tissues, including heart, brain, or skin) and perform specialized functions there (i.e., their pluri-potency or plasticity). In humans, they were first isolated in 1998 from an early embryo (or blastocyst) and successfully grown in the laboratory. Any group of cells that are so maintained for longer than 6 months are considered an established ‘cell line’, and till 2001 there were about 78 such cell lines in the world.
Most efficient stem cells are present in early (3-5 day-old) embryo, a microscopic hollow ball, consisting of a trophoblast (outer layer), blastocoel (the hollow cavity), and an inner cell mass (about 30 stem cells) in blastocoel (See Figure 1). Most human embryonic stem cells (HESC) are created with embryos from in-vitro fertilization (IVF) clinics where they are kept frozen.
HESC procedures destroy the embryo, which is the major source of moral and ethical objections from various conservative groups, besides the President. The fact that these embryos, willing created by couple with reproductive difficulties, were leftover and would eventually be destroyed doesn’t appease the objections. Even in reviving them for the initial IVF purpose, some will be lost.
Five years ago, President Bush restricted federal funding for HESC research to only those HESC lines created by the date of that announcement (9 August 2001), provided these lines were derived from an embryo created for reproductive purposes, but no longer needed, and obtained after informed consent of the donor who received no financial inducement for the purpose. This reflected the pro-life, conservative pressure from groups. Initially, under this restriction, only about 78 HESC lines were eligible. These restrictions do not, however, affect research supported by private funds, but there can be no commingling of federal funds in any shape or form. For institutions that use both sources of research funds, this was an enormous burden -- creating separate airtight compartments for federal and private research.
The other shoe fell when it became clear that more and more eligible HESC lines were so contaminated (apart from being ‘old’ and weak) that many scientists have serious doubts if the information and material obtained from them could ever be safely used for therapeutic and other purposes in humans. Now only about 21 HESC lines are eligible, which seriously limits genetic diversity. According to a 2003 survey, there are about 400,000 unwanted IVF embryos in the US. Congress recently passed a bill that would have included leftover IVF embryos donated for federal funding, but the President vetoed it.
There are other sources for stem cells, involving procedures that do not involve an embryo, and thereby wouldn’t upset the conservative groups: (i) from blood, skin and brain (or adult stem cells), which can become specialized, but only into a limited number of cell types, and they are not easy to grow in culture, (ii) from umbilical cord which contains some stem cells that can grow into heart, liver, brain, bone, or cartilage, but umbilical cord is neither long nor does it contain a big supply of stem cells, and (iii) by somatic cell-nuclear transfer (SCNT) techniques (similar to those used in creation of ‘Dolly’ the sheep), in which a skin cell is fused with an egg from which its nucleus has been removed (or enucleated), but success-rate in this is very low, requiring numerous fresh human ova which would be impractical, and it hasn’t been tried yet in humans.
Frustration has led some prominent US research groups to migrate to UK, Singapore and Taiwan. California, Connecticut and other states are trying to provide additional funding to stem the outbound tide.
Some new strategies are being developed. Harvard University is trying to develop 100 new HESCs from IVF embryos, using private funds, in addition to the SCNT procedures toward the same end. Claims by South Korean researchers of success through SCNT, later found to be not true, was a serious blow to the effort. A Kyoto University team now claims that treating skin cells by different growth factors turns them into an embryo-like entity that can provide stem cells. If true, this would bypass human embryos and make the emotional-moral argument over HESC moot. No matter the success so far or the prospects, the major hurdle still remains: human trials to test the worth of even the most successful procedures in animals.
Regardless of the prospects of HESCs for regenerative therapy, they will feature big in the mid-term elections. This issue has for once united the Democrats with a split in the Republican ranks!


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