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inhibited tumor growth and angiogenesis as well as CD45
/CD34
þ
pro-
genitor mobilization
in vivo
in a murine Lewis-lung-carcinoma-model
(
Kwon et al., 2012
).
A more positive effect was noticeable for Rosiglitazone. In a study per-
formed on CAC isolated from healthy volunteers, Rosiglitazone attenuated
apoptosis of TNF-
-stimulated CAC in a dose-dependent manner
(
Xu et al., 2011
). Further studies will presumably be directed on the anti-
angiogenic effect by blocking EPC functions. This would be of great interest
for targeting tumor lesions.
In summary (
Section 4
), EPC are mobilized from BM to PB by systemic
administration of HMG-CoA inhibitors. This effect has been proved for
simvastatine and atorvastatine but was not found after administration of ros-
uvastatine. EPC counts are elevated for the first month of the therapy but
return to lower levels after this period. There are first reports on other drugs
that blocked or attenuated the functions of EPC. These drugs could be used
as antitumorgenic therapies in order to block the vasculogenic capacities of
EPC and therefore reduce tumor growth.
a
5. EPC APPLICATIONS
5.1. Guided EPC autotransplantation
First reports on transplantation of
ex vivo
expanded EPC were published
shortly after the initial description of EPC in 1997 regarding their effects
on ischemic hind limb (
Takahashi et al., 1999
), which was followed by
descriptions of positive effects after transplantation of EPC in myocardial
ischemia (
Jackson et al., 2001; Kawamoto et al., 2001
). Just shortly thereaf-
ter, the first clinical study was conducted, which proved that the transplan-
tation of
ex vivo
purified CACwas safe and feasible (
Assmus et al., 2002
). The
long-term outcome of this study has been published as well and has revealed
a restoration of coronary flow reserve and further suggests favorable effects
on left ventricular function (
Leistner et al., 2011; Schachinger et al., 2006
).
More studies using MNC or CD34
þ
cells have been performed over the past
10 years, but the TOPCARE-AMI study is the only one that has been using
CAC for treatment in MI (
Mund et al., 2009
). Nevertheless, most of these
studies have shown more or less the same results, with no strong evidence
that EPC are performing better during transplantation after MI than MNC.
Further transplantation experiments have been performed using ECFC
or CAC. One study has used ECFC for prevention of induced pulmonary
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