Biomedical Engineering Reference
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purified BM HSCs were found in several experimental settings to be “plastic” and
able to “transdifferentiate” into various tissues as it was mentioned, although the
controversies about plasticity of hHSCs always existed [ 36, 37, 67- 69 ] . This funda-
mental discovery of a very deep pluripotent ancestor, with clearly defined and
expressed markers, and a final proven distinction between hematopoietic and non-
hematopoietic pool of adult pluripotent human stem cells, will finally improve the
chances for more successful therapeutical intervention. This will greatly help to
solve the problem of the source of pluripotent adult human cells for stem cell ther-
apy with special reference to MI and other targeted diseases such as stroke,
Parkinson's disease, spinal injury, muscular dystrophy, osteogenesis imperfecta and
many others. The cells could be then collected by mobilization (using G-CSF as
mobilizer) and apheresis and chosen fractions infused, when necessary, in order to
repair targeted: infarcted (or other) tissue(s).
Heart failure—a severe deficiency in ventricular pump function—arises through
a finite number of terminal effector mechanisms, regardless of the cause. These
include: defects intrinsic to cardiac muscle cells' contractility due to altered expres-
sion or operation of calcium-cycling proteins, components of the sarcomere, and
enzymes for cardiac energy production; defects extrinsic to cardiac muscle cells,
such as interstitial fibrosis, affecting organ-level compliance; and myocyte loss,
unmatched by myocyte replacement. Cardiac regeneration is robust for certain
organisms such as the newt and zebrafish, in which total replacement can transpire
even for an amputated limb, fin, or tail, via production of an undifferentiated cell
mass called the blastema [ 71 ]. Such a degree of restorative growth might also be
dependent on the retention of proliferative potential in a subset of adult cardiomyo-
cytes [ 72 ] and is impossible in mammals under normal, unassisted biological cir-
cumstances. Several complementary strategies can be foreseen as potentially aiding
this process: overriding cell-cycle checkpoints that constrain the reactive prolifera-
tion of ventricular myocytes [ 73 ]; supplementing the cytoprotective mechanisms
that occur naturally, or inhibiting pro-death pathways [ 73 ] ; supplementing the
angiogenic mechanisms that occur naturally using defined growth factors or vessel-
forming cells; or providing exogenous cells as a surrogate or precursor for cardiac
muscle itself [ 74 ]. Among these conceptual possibilities, cell implantation in vari-
ous forms has been the first strategy to be translated from bench to bedside. The
promise of cellular cardiomyogenesis and neovascularization, individually or in
tandem, offered altogether novel opportunities for treatment, tailored to the underly-
ing pathobiology.
Within past several years, more than a half-dozen early clinical studies have been
published, ranging from case reports to formal trials, deploying a range of differing
cell-based therapies with the shared objective of improving cardiac repair [ 25, 28,
75- 80 ]. Clinical follow-up for as long as a year is now available for some patients.
Despite their different strategies and cells, and lack of double-blinded controls,
these small initial human trials in general point to a functional improvement; yet key
questions remain open. Understanding better just why and how grafting works will
be essential, alongside needed empirical trials, to engineer the soundest future for
regenerative therapy in human heart disease.
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