Endogenous stem cells may help repair injured myocardium, says lab
evidence
August 24, 2007 Steve Stiles
New York, NY - Protect your healthy cardiomyocytes, they may be all
you ever have—unless some are injured and replaced by myocytes that
develop from stem cells, suggests a study in experimental models of
acute MI and hypertensive hypertrophy [1].
In a series of experiments in transgenic mice, heart-muscle cells
that had been tagged with a genetic marker and then subjected to
injury were apparently replaced by new untagged ones, but there was
no evidence of such myocyte replacement in the hearts of mice that
had aged normally for a year, report Dr Patrick CH Hsieh (Brigham and
Women's Hospital, Boston, MA) and colleagues.
In a report published in the September 2007 issue of Nature Medicine,
the group says their findings are consistent with the existence of an
endogenous myocardial repair mechanism that could potentially be the
basis for new treatments. What they don't actually show, they write,
is what precursor cells may be involved in the replacement of injured
cardiomyocytes.
"There was evidence for some stem-cell pool becoming new heart cells
that diluted the older ones. We can't tell where they came from;
that's a huge question for the scientific community," coauthor Dr
Richard T Lee (Brigham and Women's Hospital) told heartwire. The
findings, however, "suggest that the regeneration machinery is there,
at least in mice. That's good news for us, that we have this
capability locked within the heart. If we can unlock it and amplify
it, hopefully we can regenerate enough myocardium to improve or
prevent heart failure."
The group created a line of transgenic mice with intracellular
expression of a myocyte-specific protein that can be chemically
induced to enter the nucleus, Lee explained. When that happens, the
protein triggers a genetic recombination that stops the expression of
beta-galactosidase and starts the expression of green fluorescent
protein (GFP), which permanently tags the myocytes in a way that
allows them to be traced and quantified.
By treating the mice with the chemical inducer, 4-hydroxy tamoxifen,
the investigators were able to achieve GFP expression in, on average,
83% of a heart's myocytes.
That proportion of GFP-positive cells didn't change significantly
after up to a year of normal aging—about half the lifetime of a
mouse, Lee observed—suggesting an absence of cardiomyocyte turnover
from any sort of stem-cell-mediated regenerative process.
But the story was different in the hearts of mice that had been
subjected to experimental infarction or pressure overload by
transverse aortic constriction. Compared with the hearts of mice that
underwent a sham procedure, which served as controls, those with
experimental injury eventually showed significant declines in the
proportion of GFP-positive myocytes, "indicating that stem cells or
precursor cells had refreshed the cardiomyocytes,
The declines in GFP-positive myocytes were steepest in tissue near
infarct borders and, in both models of heart injury, balanced by an
increased proportion of cells expressing beta-galactosidase.
The next important step, Lee said, would be to identify the source of
the replacement cells, perhaps in similar genetic fate-mapping
studies involving labeled cardiac progenitor cells.
Source
Hsieh PCH, Segers VFM, Davis ME, et al. Evidence from a genetic fate-
mapping study that stem cells refresh adult mammalian cardiomyocytes
after injury. Nat Med 2007; 13:970-974.
Related links (live on the source below)
Cardiomyocytes regenerate after MI in rat study
[HeartWire > News; Oct 09, 2006]
Even end-stage hearts have cardiac stem cells capable of myocardial
regeneration
[HeartWire > News; Jun 01, 2005]
Adult cardiomyocytes capable of division and proliferation
[HeartWire > News; May 02, 2005]
Progenitor cells discovered in the postnatal heart
[HeartWire > News; Feb 16, 2005]
http://www.theheart
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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