March 31, 2010 | David F. Coppedge

Stem Cells Promise Regeneration

Imagine being able to grow a new limb or jaw.  Adult stem cells may one day make possible something almost unimaginable in hospitals today: the regeneration of new limbs or organs.  There’s growing evidence, too, that mammals once had a regenerative potential that has been lost.
    Hydras do it.  Salamanders do it.  Why can’t mammals regrow damaged limbs?  Science Daily reported this month that a gene has been identified in mammals involved in regeneration: “A quest that began over a decade ago with a chance observation has reached a milestone: the identification of a gene that may regulate regeneration in mammals,” the article said.  “The absence of this single gene, called p21, confers a healing potential in mice long thought to have been lost through evolution and reserved for creatures like flatworms, sponges, and some species of salamander.”  Why evolution would ever lose something so beneficial was not explained.  But without p21, cells in a mouse’s damaged tissue began acting like embryonic stem cells and started differentiating into new tissue without forming a scar.
    Scientists at the Wistar Institute found this by accident in 1996.  They routinely pierce holes in the ears of lab mice for identification.  They found the ear holes on those with p21 knockout genes healed without a trace.  One researcher said, “Much like a newt that has lost a limb, these mice will replace missing or damaged tissue with healthy tissue that lacks any sign of scarring.
    This raises a question of why the p21 gene exists if its absence confers a benefit.  It turns out there is a delicate balance between the cell cycle, regeneration and cell death.  “In normal cells, p21 acts like a brake to block cell cycle progression in the event of DNA damage, preventing the cells from dividing and potentially becoming cancerous,” Dr. Ellen Heber-Katz of the Wistar Institute explained.  But this gene’s role must be considered in context: “The down regulation of p21 promotes the induced pluripotent state in mammalian cells, highlighting a correlation between stem cells, tissue regeneration, and the cell cycle.”  Because we know that regeneration works in salamanders and other organisms, it may be possible to steer these processes toward the repair of damaged limbs.  Think of the potential for athletes, soldiers and accident victims.
    Scientists at Duke University are making headway in regenerative medicine, too.  Science Daily reported that they “identified a new growth factor that stimulates the expansion and regeneration of hematopoietic (blood-forming) stem cells in culture and in laboratory animals.”  The protein they identified that can stimulate expansion of adult stem cells from umbilical cord blood or bone marrow may also have application in regeneration.  “Perhaps more importantly, systemic treatment with pleiotrophin may have the potential to accelerate recovery of the blood and immune system in patients undergoing chemotherapy or radiotherapy,” Dr. John Chute of Duke University said.  So far he has not seen the accelerated stem cells become malignant.
    According to another story reported by Science Daily, regenerative potential exists not just in stem cells, but in mature cells, too.  Scientists at Salk Institute for Biological Studies and the Center of Regenerative Medicine in Barcelona are hot on the tail of zebrafish, trying to figure out how they can regrow heart muscle.  “What the results of our study show is that mother nature utilizes other ways besides going all the way back to pluripotent stem cells to regenerate tissues and organs,” one of the Barcelona scientists said.  They found they could chop off 20% of the ventricle of a zebrafish heart and it would grow back, young and fresh as new.  Why can’t human hearts do that?  Why is our damaged heart tissue replaced with scar tissue?  In trying to find out, the scientists are suggesting that tissue regeneration could be coaxed with a little push in the right direction: “forced expression of cell cycle regulators can induce cardiomyocyte proliferation in mammals.”  The director of the CRMB said, “If we could mimic in mammalian cells what happens in zebrafish, perhaps we could be in a position to understand why regeneration does not occur in humans.”
    Today, Science Daily announced an even more dramatic regeneration story: a jaw bone grown from adult stem cells.  “A Columbia scientist has become the first to grow a complex, full-size bone from human adult stem cells,” the surprising subtitle declared.  Specifically, a tempero-mandibular joint was grown on a scaffold acting as a template for stem cells from bone marrow.  “Wouldn’t it be wonderful if we could get the patient’s own stem cells and grow a new jaw?” said Dr. June Wu, a craniofacial surgeon.  Currently, pieces of bone are taken from a patient’s hip or leg to replace facial injuries.  The lab still has to figure out how to connect the graft to the patient’s blood supply, but imagine surgeons some day being able to put a framework in place of a broken joint or bone, injecting it with your own stem cells, and getting it to grow back just like new.
    The hydra genome was sequenced recently.  This is an organism that, despite its small size and apparent simplicity, is a master of regeneration.  Science Daily said the study of the hydra “continues to advance research on regeneration, stem cells and patterning.”  Did you know this little organism has about as many genes as a human being?  If it can regrow parts, why couldn’t we?  Dr. Robert Steele of UC Irvine said, “Having the Hydra genome sequenced also enhances our ability to use it to learn more about the basic biology of stem cells, which are showing great promise for new treatments for a host of injuries and diseases.
    The University of Rochester Medical Center is looking into how to prepare adult mesenchymal stem cells and keep them ready for use, reported Science Daily.  They want these amazing regenerative cells to be available in the right condition and at the right time for treatment of knee injuries, osteoporosis, or whatever: “stem cells that create bones, cartilage, muscle and fat.”  It’s part of a medical bonanza in progress: “The work is part of ongoing research around the world aimed at harnessing the promise of stem cells for human health.”
    Note that none of these stories talked about embryonic stem cells.  Most of the stories about embryonic stem [ES] cells this month discussed efforts to understand how they grow and differentiate (e.g., Science Daily, PhysOrg, PhysOrg).  Some mentioned promises of possible treatments in the distant future (e.g., Science Daily), but none of them mentioned any realistic new treatments for human disease.  Another article on Science Daily worried that human ES cells may be much more different than mouse ES cells than was previously believed, making tests based on a mouse model “pointless — and sometimes even misleading.”  Even with nothing practical to show for it, though, Science Magazine’s Insider Blog reported that “Congressional supporters of stem cell research have introduced legislation to codify President Barack Obama’s 2009 executive order, which lifted restrictions on the number of human embryonic stem cell lines available to federally funded researchers.”  Meanwhile, Science Daily said that amniotic fluid stem cells can be reprogrammed to pluripotency efficiently, “where they have characteristics similar to human embryonic stem cells that can develop into almost any type of cell in the human body” – so are ES cells, with ethical clouds surrounding them, even needed any more?
    Let’s end this entry with another miracle-cure story from adult stem cell research: PhysOrg reported this month, “University College London scientists and surgeons have led a revolutionary operation to transplant a new trachea into a child and use the child’s own stem cells to rebuild the airway in the body.”  The boy is recovering and breathing on his own.  Because the boy’s own stem cells were used, there is no problem of rejection.  A doctor said, “We have shown that stem cell-based treatments can save lives and can be used in the creation of living structures which draw upon the body’s own natural healing mechanisms for their support.”  Need more good news for the encore?  “The step-wise progression in technique from first patient to the present has delivered a highly streamlined, rapid process.  This means that such treatments potentially can be moved out of the hands of a tiny number of specialist centres into many hospitals around the world, including those in developing countries.
Update 03/31/2010: No sooner did this entry go to press but PhysOrg gave news that may make the song Three Blind Mice obsolete: “Gene therapy restores vision in mice,” the headline announced.  “Scientists from Buffalo, Cleveland, and Oklahoma City made a huge step toward making the blind see, it said.  They found that inserting DNA nanoparticles appears hopeful for curing inherited and acquired vision disorders that cause blindness, like retinitis pigmentosa.  “Making the blind see was once called a miracle,” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal.  As we have expanded our understanding of evolution, genetics, and nanotechnology, chances are that ‘miraculous’ cures will become as commonplace as those claimed by faith-healers past and present.”  Aside from begging the question what the word miracle means (or what an understanding of evolution has to do with it), this treatment involves the returning genetic information where it is needed.
    Simultaneously, Nature News announced good news for burn victims and other people needing help with repairs on the largest organ of the human body: the skin.  “The identity of a stem-cell type that gives rise to different epidermal-cell lineages has just been revealed.”  Called bulge stem cells, they provide the “first evidence that skin stem cells can differentiate into interfollicular epidermis, sebaceous gland and hair follicle lineages.”  Harnessing and steering these cells may lead to treatments that “help with the rapid regeneration of the wounded skin.”
    Did we say bonanza?  Don’t read the New Scientist article about regenerating brain neurons with stem cells, or you may get overstimulated.  Jeff Macklis at MIT is thinking about neurogenesis with adult stem cells as a possible treatment for dementia and other brain disorders.  Caution is in order, of course: “the nervous system was built with precision,” he said, “and we will have to rebuild it with that precision.”
Update 04/01/2010: The father of induced pluripotent stem cells [iPS] was honored again.  In its “Random Samples” for April 2, Science said that Shinya Yamanaka won the $250,000 March of Dimes prize.  “Rapidly evolving iPS cell technology not only potentially eliminates the need to destroy human embryos for stem cells; it also has, in effect, democratized the field by making it possible for any cell biologist to work with pluripotent human stem cells.”

These bittersweet stories – sweet for the lifesaving treatments coming from adult stem cells, bitter for the incorrigible attachment of some scientists and politicians to cutting up human embryos for no good reason – are mostly sweet.  It appears that many research teams are following the promising leads with adult stem cells.  The interest in embryonic stem cells seems to have dimmed considerably, but we need to keep the addicts in check.  It’s no coincidence the staunch proponents of ES research are often far left politically – and support unlimited abortion; sometimes worse (euthanasia, death panels).  In a particularly disgusting example, leftist New York Times columnist Paul Krugman agreed that “Death panels would save money.”  He said of advisory panels making end-of-life decisions on whether to grant expensive treatments or not, “That is actually going to save quite a lot of money” (see World Net Daily).  Follow the people who love and respect human life.  The work on adult stem cells illustrates how science should be done: increasing understanding of natural processes for the purpose of benefiting human life.
    Switching gears, let’s think a little about the original creation.  These thoughts are admittedly speculative, but the possibility of restoring the capability of regeneration in mammals suggests that it used to exist.  Are we to believe the Darwinians’ ridiculous assertion that this “healing potential” was “lost through evolution”?  Why would evolution lose something so precious?  The original creation may have included the ability to recover completely from accidental damage.  After all, we do have such mechanisms, such as the blood clotting cascade, and we see regeneration working in the hydra and amphibians.  Automatic healing may have included internal factors (regeneration via stem cells) and external factors (the Tree of Life, for the healing of the nations, Rev. 22:1-3).  A Biblical creationist could account for loss of function because of the curse on sin.  In fact, much of medicine amounts to trying to regain ground from the cumulative effects of millennia of decay – mutations, sin, and a deteriorating environment.  There have also been genetic bottlenecks (the Flood) that could have squeezed out other health capabilities that may have existed in the first generations of people, before mutations accumulated and became fixed in the post-Flood remnant.  Original healing mechanisms might account for maintenance of an entropic world, since it is difficult to imagine a universe without a Second Law of Thermodynamics.
    With these considerations in mind, it can be seen that recapturing lost capabilities, like limb and organ regeneration, is a morally good, though temporary, solution.  Jesus Christ went about healing and doing good (even regenerating limbs and organs), knowing that the recipients of his grace would die eventually anyway.  His example shows that, even though death is inevitable, alleviating suffering is worthwhile.  What we really need, though, and what Christ focused on, was spiritual regeneration.  That treatment is already tested, working, paid for, and available to all (Titus 3:4-7).  Get your heart transplant today.

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