November 24, 2014 | David F. Coppedge

Adult Stem Cells Beat Clones

In a contest to see which are better, induced pluripotent stem cells proved just as good as clones.  More stem cell news follows.

Stem cell recipes went head to head, Science Magazine reported, and came out in a tie.  Kelly Servick writes:

What’s the best recipe for creating patient-specific stem cells? The question has prompted years of debate and a series of contradictory papers. Ideally, the cells should develop into any cell type just as well as those in a natural embryo do. For now, the 7-year-old method of introducing a small set of genes into adult cells to create so-called induced pluripotent stem (iPS) cells dominates the field. But a few researchers have stuck with an older approach—putting a donor nucleus into an unfertilized egg and deriving stem cells from the resulting embryo. This somatic cell nuclear transfer (SCNT) technique is costly, technically challenging, and ethically fraught on several fronts. But proponents have argued that cells created this way are superior, in part because iPS cells may retain features of mature cells and could acquire a greater number of genetic changes in the reprogramming process. The latest research on the matter, published this week in Cell Stem Cell, examines genetic features of the two cell types and declares a tie.

That might surprise some people, because the researcher who led the work, Dieter Egli of the New York Stem Cell Foundation (NYSCF) in New York City, has long been a proponent of nuclear transfer. He gave a preview of the paper on 22 October at the foundation’s annual conference. “This means that all of you who are working on iPS cells are probably working with cells that are actually very good. So I have good news for you,” he told them, eliciting murmurs and chuckles. “What this exactly means for the SCNT program, I don’t know yet.” Indeed, some longtime champions of the nuclear transfer—Egli included—aren’t ready to abandon the method yet.

Science Daily reports that the New York Stem Cell Foundation finds the two types of stem cells “very similar” in terms of DNA methylation, mutations, and gene expression patterns.  Since iPS cells are “not ethically fraught” at all, it would seem SCNT should declare no contest.  The articles do not give any clear reason why cloning should be continued; but proponents like Mitalipov are vowing to defend their work.

The New York foundation claims that embryonic stem cells are still superior.  “It is important to note that both types of techniques led to cells that had more of these aberrations than embryonic stem cells derived from an unfertilized human oocyte, or than embryonic stem cells derived from leftover IVF embryos,” Science Daily says.  “These findings suggest that a small number of defects are inherent to the generation of stem cells from adult differentiated cells and occur regardless of the method used.”

The question becomes whether it is advisable to destroy human embryos to heal those already born into the world, if iPS and adult stem cells are sufficient for therapeutic needs.  If adult stem cells from a 97-year-old  person’s cornea can heal retina damage (10/22/14), why take them from the unborn?  Why not instead, as PhysOrg reported, study how embryos produce their stem cells and use those secrets to reprogram adult cells?  A story in Science Daily shows how researchers are constantly refining methods for iPS, but SCNT-derived stem cells are not without problems.

In the meantime, iPS and adult stem cells continue to show great promise for human health.  The smart money goes to ethically-clean methods.

  1. Brain injuries in mice treated using bone marrow stem cells, antioxidants (Science Daily): Stem cell treatment combined with drug therapy shows regeneration of brain tissue and the blood vessels supporting them.
  2. Reprogramming cells, long term (Science Daily): Harvard scientists “have demonstrated that adult cells, reprogrammed into another cell type in a living animal, can remain functional over a long period.
  3. iPS cells used to understand schizophrenia (Nature): “We showed that mutant DISC1 [a schizophrenia marker] causes synaptic vesicle release deficits in iPS-cell-derived forebrain neurons,” researchers at Johns Hopkins found.  “…Our study reveals that a psychiatric disorder relevant mutation causes synapse deficits and transcriptional dysregulation in human neurons and our findings provide new insight into the molecular and synaptic etiopathology of psychiatric disorders.”
  4. Remotely controlled magnetic nanoparticles stimulate stem cells to regenerate bones (PhysOrg): “Medical researchers from Keele University and Nottingham University have found that magnetic nanoparticles coated with targeting proteins can stimulate stem cells to regenerate bone,” the article says. “Researchers were also able to deliver the cells directly to the injured area, remotely controlling the nanoparticles to generate mechanical forces and maintain the regeneration process through staged releases of a protein growth stimulant.”  Presumably the stem cells come from the patient’s own body.
  5. Establishment of induced pluripotent stem cells from Werner syndrome fibroblasts (Science Daily): Werner syndrome causes patients to age rapidly; now, “genome editing” of patient-derived stem cells offers new hope.  “Induced pluripotent stem (iPS) cells from Werner Syndrome fibroblasts have been established, scientists report.”
  6. Making personalized blood vessels from a patient’s blood sample (Science Daily): Swedish researchers rebuilt blood vessels from blood stem cells, without having to drill into bone marrow, which is painful.
  7. Delivery of stem cells into heart muscle after heart attack may enhance cardiac repair and reverse injury (Mt. Sinai Hospital): “A novel SCF gene transfer delivery system induced the recruitment and expansion of adult c-Kit positive (cKit+) cardiac stem cells to injury sites that reversed heart attack damage. In addition, the gene therapy improved cardiac function, decreased heart muscle cell death, increased regeneration of heart tissue blood vessels, and reduced the formation of heart tissue scarring.”
  8. Technology to advance stem cell therapeutics patented (Rutgers U): “Our motivation was to develop a highly robust, efficient nanoparticle-based platform that can regulate gene expression and eventually stem cell differentiation,” says Ki Bum-Lee, who developed NanoScript for that purpose.  NanoScript uses gold nanoparticles to mimic the transcription factors that regulate stem cell differentiation.
  9. Production of human motor neurons from stem cells gaining speed (PhysOrg): Researchers at the Institute for Stem Cell Therapy are finding new ways to rapidly produce large quantities of human pluripotent stem cells.  “In the medium term, the approach should contribute to the development of treatments for paralytic diseases such as infantile spinal muscular amyotrophy or amyotrophic lateral sclerosis.
  10. Nail stem cells prove more versatile than press-ons (University of Southern California): Think about it; your fingernails grow, don’t they?  That’s because of an “elusive” source of stem cells that produce both nails and skin.  USC researchers made a “surprising discovery,” the press release says; they “identified a new population of nail stem cells, which have the ability to either self-renew or undergo specialization or differentiation into multiple tissues.”

What is the ultimate stem cell?  An article on Medical Xpress indicates that embryonic stem cells may not be very much ahead of iPSCs, the stem cells reprogrammed from adult tissues.  Researchers at the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute compared the two.  The director was asked if embryonic stem cells are better:

Could naive human ES cells be the stem cell of choice for tissue therapy? “We don’t yet know,” said Smith. “These cells would offer the hope of having a broader and more consistent ability to differentiate into a range of cell types because they are at an earlier stage of development. But it’s also entirely possible that current stem cells are good enough for some applications. The point is, we needed these new stem cells in order to find out what is best.”

But those nagging ethical issues remain.  In “The ethical, legal and political minefield of stem cell research,” PhysOrg reminds readers that the “Great Debate” about using human embryos for research “has been the subject of comment, criticism and even court cases.”  With its recounting of the strong opinions voiced on both sides, the patent debates and the ethical outcries over what constitutes a human, the article is a sad reminder of the hand-wringing that still goes on over ESC research.  When there is more than one way to reach a destination, wisdom dictates walking around the minefield when possible.  That’s the path adult stem cell technology takes.

Update 11/24/14: Harvard scientists failed to get embryonic stem cells to form neurons, until they tried induced pluripotent stem cells, reports Science Daily.  “I think the ability to make human pain neurons for the pain field is going to be very important,” Clifford Woolf says.  “Furthermore, our failure with embryonic stem cells lead us to work with adult tissue samples making the technology much more clinically relevant since these are easy to collect from patients suffering from different kinds of pain.”  This is important for showing that iPS cells can actually perform better than embryonic stem cells.

Can anyone find a really good reason for using human embryos in the burgeoning field of stem cell therapeutics?  The only claim is that they are totipotent, able to generate any tissue in the body, and iPSCs are pluripotent—something less.  Even that argument is not clear, though.  Each new discovery appears to show adult stem cells throughout the body—in the cornea, brain, bone marrow, placenta, mesenchyme, heart and elsewhere—that can be activated in place or relocated where needed.  And then there is reprogramming, using iPSC methods to turn skin cells into stem cells.  The toolkit seems plenty adequate for desired therapies, and it’s getting better all the time.  The burden of proof should be on the SCNT and ESC researchers to show why they deserve any money or respect.


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