Biomedical Engineering Reference
In-Depth Information
directly into the heart muscle using a specialized catheter (Biocardia Inc) inserted
through a tiny puncture in an artery, a procedure similar to other cardiac catheter-
ization techniques. Use of this catheterization technique was shown to be safe and
effective. Its use increases the options for delivering stem cell therapy in the future;
most existing studies use intravenous injections. If further animal studies and
human clinical trials prove equally successful, the investigators believe this could
be a new, widely applicable treatment to repair and reverse the damage done to
heart muscle that has been infarcted, or destroyed, after being deprived of its blood
supply. Using MSCs also avoided potential problems with immunosuppression, in
which each animal's immune system might have attacked SCs from sources other
than itself. Because they remain in an early stage of development, MSCs do not
trigger an immune response, unlike what would happen if more developed SCs
were used. Among many benefits of this approach are that adult SCs are readily
available, that is, they can be extracted from the patient, no donor is required, and
the cells can be simply reproduced if more are needed. This study forms the basis
of a clinical trial of autologous MSCs in patients with myocardial infarction.
In 2001, MSCs from a man's bone marrow were microinjected directly into the
tissue of his heart during coronary artery bypass grafting at the Clinic of Cardiac
Surgery in Rostock, Germany. No complications were detected after the procedure,
and the physicians have performed the same operation on other patients. In 2005,
ten clinical trials started in the USA to test MSCs (Osiris' Prochymal) for acute
myocardial infarction.
In 2006, University of Rochester (Rochester, NY) started a multicenter randomized,
double-blind, placebo-controlled, phase I clinical trial with patients randomized to
receive either an injection of 0.5 million, 1.6 million, or 5.0 million cultured adult
MSCs (Osiris Therapeutics' Prochymal) per kilogram of body weight, or placebo.
All patients received standard treatment, including techniques to maximize blood
flow to damaged areas, pain relief, oxygen, anticoagulants, b-blockers, nitrates,
ACE-inhibitors, and advice on reducing risk factors. Trial entry occurred within
10 days of first heart attack, and patients were followed for 2 years afterward. The
results, published in 2009, are described later in this chapter.
A key issue with the use of MSCs is the development of a suitable system for
their delivery to the site of infarction. One delivery system uses a fibrin-based patch
to entrap cells during polymerization. This delivery vehicle has many advantages;
however the mechanical properties and the limited capacity for tailoring cell
response may restrict its application. A PEGylated fibrin patch for MSC transplan-
tation was developed by modifying fibrinogen with the benzotriazole carbonate
derivative of PEG to create secondary crosslinking (Zhang et al.
2006
). This
PEGylated fibrin patch increases MSC viability and produces phenotypic changes
in MSCs consistent with endothelial cells.
In Vivo Tracking of MSCs Transplanted in the Heart
In vivo trafficking of allogeneic MSCs colabeled with a radiotracer and MRI con-
trast agent has been dynamically determined in acute myocardial infarction by use
of the high sensitivity of a combined SPECT/CT scanner (Kraitchman et al.
2005
).
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