Biomedical Engineering Reference
In-Depth Information
Table 12.2
MSCs used for tumor delivery of anticancer agents.
Cytokines
and
chemokines
Animal model
Results
Ref.
d
n
4
y
3
n
g
|
1
10
IL-2
Rat glioma model
Gene modification of MSCs by
infection with an adenoviral vector
encoding human interleukin-2 (IL-2)
augmented the antitumor effect and
prolonged the survival of tumor-
bearing rats.
110
IL-12
Mouse xenograft
model of renal cell
carcinoma (RCC)
Systemic administration of MSC/IL-12
reduced the growth of 786-0 RCC
and significantly prolonged survival
of tumor-bearing mouse.
74
IFN-b
Mouse prostate
cancer lung
metastasis model
A significant reduction in tumor
volume in lungs following IFN-b
expressing MSC therapy.
73
TRAIL
Mice metastatic lung
tumors
(MDAMB231)
TRAIL-expressing MSCs were able to
reduce tumor growth and clear the
metastatic disease.
55
CX
3
CL1
Mice metastatic lung
tumors (LLC)
Intratracheal administration of MSCs
expressing CX
3
CL1 suppressed the
growth of multiple lung metastases
and prolonged survival in mice.
111
CCL5
Mice primary
pancreatic tumor
The active homing of MSCs into
primary pancreatic tumor stroma
and activation of the CCL5
promoter was verified using eGFP-
and RFP-reporter genes. In the
presence of ganciclovir, HSV-Tk
transfected MSCs led to a significant
reduction of primary pancreatic
tumor growth and incidence of
metastases.
Immunohistochemical examination of the lung tissue demonstrated an increase
in tumor cell apoptosis, and a decrease in both tumor cell proliferation and
blood vessel counts. A significant increase in the natural kill cell activity was
observed following IFN-b therapy, correlating the antitumor effect. The
systemic level of IFN-b was not significantly elevated from this targeted cell
therapy. These data demonstrate the potential of MSC-based IFN-b therapy
for prostate cancer lung metastasis.
74
Currently, most studies on gene-modified MSCs for the treatment of tumors
use viral vectors for gene transfer.
75
However, they may be associated with
safety problems. Recently, we employed the nonviral vector polyethylenimine
(PEI) to transfer IL-12 into MSCs for the treatment of lung metastases in
C57BL/6 mice, and found that MSC-IL12 injected mice showed significantly
less lung metastases numbers compared with the direct injection of IL-12 and
