On March 9, 2009, President Obama lifted some sanctions initially imposed during the George W. Bush presidency on the study and use of human embryonic stem cells, a development of great importance for the new field of regenerative medicine.
Regenerative medicine today largely focuses on using cultured stem cells to replace adult specialized cells that are no longer operating well, or operating at all.
The causes for the cellular malfunction or absence may be damage from infectious diseases or trauma, collateral damage from tumor removal, x-ray or chemotherapy treatments, as well as inherited diseases.
But most often the need for cell replacement appears to be age-related.
Why do Cells Need to Be Replaced?
There is overwhelming evidence that specialized cells in adults lose much of their ability to divide into health functioning cells with time.
Yet transplanting wholly mature and specialized cells that perform the same function as the adult cells that are failing in an organ or body part has been only marginally successful to date.
Immunological rejection and the fact that the transplanted older cellular materials may themselves senesce, has often lead to rather short-terms restorative gains, if there are any gains at all.
The transplanted cells undergo only so many cell cycles of mitosis and then shut down.
Why are Stem Cells Good Candidates as Replacement Cells?
Stem cells share a property with many cancer cells. They can multiply forever, given the right environment and nutrients. In a sense, they are a self-perpetuating source of raw material for eventual cell replacement therapies.
Just as importantly, stem cells have the ability, with the right prompting, to transform themselves into specialized cells that can be transplanted.
The theory is that they will remain vital longer than do the usually transplanted adult cells and tissues, and sometimes they do not provoke immunological rejection as soon or as extensively.
The union of these two abilities basically means that, if all things go well, the regenerative physician-scientist has a kind of cellular clay deposit that replenishes itself and that clay can be spun and fired into a wide variety of specialized pots and vases, that subsequently hold up well.
Are All Stem Cells The Same?
There are two basic types of stem cells.
By far, the most promising to date have been human embryonic stem cells. These show the greatest flexibility in what kinds of cells and tissue they can be made to become in the lab.
These cells are obtained, as their name suggests, from donated fertilized human embryos (usually “surplus” embryos that the mother-to-be now feels no need for keeping around because she has already had a successful pregnancy or pregnancies).
These intact embryos are sacrificed, by being torn apart, at an early stage of their development, when the cellular components retain the essential quality of being unspecialized or more technically “undifferentiated.”
The now separated embryonic cells are plated onto petri dishes, where, with the right growth medium, they thrive, until they are directed to develop into the more specialized cells that are required.
However, there are also adult stem cells. These have been derived from bone marrow, liver lobes, fat deposits, skin, umbilcal cords, and other tissues.
A key difference in their processing is that in many instances they have to have their “inflexible” adult specialization knocked out of them through switching off some of their regulatory genes.
In other words, they have to lose the ability to do certain highly specialized tasks that are “used to doing” in order to be retrained.
In return for this, they assume a child-like plasticity to grow in petri dishes with much the same vigor as do the embryonic stem cells, and after a time, they can be re-programmed into the cells that are needed for a particular patient’s replacement needs.
Reprogrammed adult stem cells actually have the possibility of being derived from the very patient who needs the cell replacement, meaning that they have the potential to have almost zero chance of being rejected.
What Obstacles Need to Be Overcome in Order for Stem Cell Research to Fulfill its Clinical Promise?
There is no getting around the fact that many people, even those who are scientifically very well-informed, feel that destroying human embryos is destroying human life, and are therefore opposed to this line of research on moral grounds.
Those who disagree with that argument say that the embryos would likely be destroyed anyway, so that there is no point in letting them go to waste.
The counterpoint to that argument is that a market will develop for producing human embryos directly for embryonic stem cell research, and support for the idea and underlying cell culture technology of cloning humans embryos will be accelerated.
Apart from the moral arguments, there is an unfortunate, and occasionally observed tendency of some introduced embryonic stem cells to form tumors rather than healthy functioning replacement tissues, and as yet this cannot be predicted or controlled.
Some of the most intensive work today is focused on characterizing markers (usually cell surface proteins) for healthy versus suspect stem cells, and for identifying subpopulations of stem cells that seem more promising than others.
Because, without marker screening, the embryonic stem cell cure could be as bad or worse than the disease.
Finally, two essential stem cell and tissue engineering technologies need to be greatly expanded.
The first is the enhanced tailoring of the chemical, physical and even dynamical environments (petri dishes shaken or not shaken, rotated or not rotated, inverted or right-side-up, with structural scaffolds or without them) of the undifferentiated cell cultures, so they can be induced to be exactly the right kinds of specialized cells.
There are conceivably hundreds of different specialized cells that are needed, but not yet hundreds of surefire ways of making them, to the exclusion of other cell types.
Second, even once the right types of cell are arrived at in pure culture, how are they to be stored before being administered, and in what medium are they to be administered?
Right now, many stem cells are apparently being frozen for storage, but it is not clear that this does not sometimes destroy or alter the functionality of some of the stem cells after thawing.
Means of administration of stem cells include the development of solutions that will not kill either the stem cells or the tissues surround the site of injection.
This is a serious consideration because different sites in the body have subtly different biochemical pH balances, ionic concentrations, and mechanical pressures involved.
Likewise, time-release gels or sponge-like matrices are being developed so that the cells are released more gradually, or so that they will not be attacked by adverse conditions on site before they can become established.
What Are The Types Of Condition Or Body Parts That Are Under The Most Study?
The list of target diseases is growing. By far the greatest level of research has been in areas of neuroregeneration, for conditions like Parkinson’s disease and spinal cord injury.
Coming in at something like second place is diabetes research, followed by bone and joint work, especially cartilage repair.
Work on eye diseases and the kidney have been less common, but are increasing.
But the greatest surge in recent months has been in revascularization of damaged heart tissue and cardiac vessels.
More diseases and organ systems are likely to be targeted for a stem cell program, given that some restrictions that have limited the embryonic stem cell side have been swept aside.
Progress in basic understanding and prototypical storage and delivery systems will accelerate.
When will actual “cures” be had?
The best guess is somewhere in the 10-15 year range.
Tony Stankus tstankus@uark.edu Life Sciences Librarian & Professor
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There is no words to explain the success stories of stem cell therapy in curing diseases from diabetes to Alzhemiers!
Posted by: Living Cell Therapy | June 25, 2009 at 11:56 PM
Regenerative medicine will help to produce extended healthy longevity, as we will be able to repair some of the damage caused by aging, organ by organ.
Posted by: tin whiskers | June 06, 2009 at 03:07 AM