Biomedical Engineering Reference
In-Depth Information
systolic function [
76
]. Finally, reports have shown that angiogenic factors can pro-
mote localized angiogenesis in vivo when administered in a nano- or micropartic-
ulate depot [
77
,
78
]. Particles prepared with the Poly(lactic-co-glycolic acid)
(PLGA) copolymer have been widely used due to the excellent biocompatibility and
biodegradability of the material [
79
-
83
]. Benefits of using PLGA particles for
angiogenesis have been shown in hindlimb ischemia models, resulting in increased
blood vessel formation [
84
-
86
]. Also, the effect of delivery of PLGA microparticles
loaded with VEGF-A
165
has been studied in a rat model of cardiac ischemia-reper-
fusion, demonstrating an increase in heart tissue angiogenesis and arteriogenesis,
besides positive remodeling of the heart [
63
]. Moreover, PLGA has been also used to
encapsulate heat shock protein 27 (HSP27), which exerts protective effects in cardiac
cells under hypoxic conditions [
87
]. Finally, PLGA microparticles have also been
combined with other delivery systems in order to optimize the patterns of growth
factor controlled release. Alginate gel/PLGA microsphere combination system
containing VEGF enhanced the angiogenic response after hind limb ischemia in rats
[
84
] and mice [
85
]. This combination system also allowed a dual delivery strategy
and improved the effects of single factors.
The different growth-factor delivery systems listed above constitute an important
body of intensive efforts to overcome the limitations of protein-based therapy for
therapeutic angiogenesis. The protein threshold concentration and its local exposure
duration remain to be determined and still represent the paramount challenge.
Over the past years, many growth-factor delivery strategies have been tested in
preclinical studies. However, little information on clinical settings using protein
delivery systems is available. Controlled release of FGF-2 encapsulated in heparin-
alginate pellets led to significant angiogenesis with low systemic effects in patients
undergoing bypass surgery, but this approach did not alleviate operative risks [
88
].
Therefore, further clinical trials to evaluate the effects of treatment induced by
controlled growth factors delivery methods may be necessary.
5.3 Stem Cell Therapy for Cardiovascular Disease
One of the main problems in cardiac disease is that the regenerative capacity of the
heart is very limited compared with other high regenerative organs like the liver,
skeletal muscle, or skin. Some mathematical models have suggested that only
0.4-1 % of the cardiomyocytes are renewed per year [
89
]. Thus, the heart tissue can
hardly regenerate after an ischemia episode where up to 25 % of the cardiomyocytes
of the human left ventricle can be wiped out in a few hours [
90
]. A similar problem
occurs in other disorders such as hypertension or valvular heart disease [
91
].
Nowadays, there is no treatment able to restore the injured heart and stem cell
therapy has become a new option to rebuild the damaged myocardium [
92
]. In the last
two decades, many studies have been performed in order to identify and characterize
many stem cell populations, also testing their potential to regenerate the infarcted heart.
Different cell types derived from a wide variety of adult tissue sources like the bone
