Biomedical Engineering Reference
In-Depth Information
trials), the variation in cell products, the lack of a control group (unless for the
Russian study, but it is striking that no data about patients complexity are pro-
vided) and the limited information provided about additional therapies. It is worthy
to highlight that the definitive results of Prochymal
TM
phase II trial, with a big
company support, have not yet been published despite the authors are reporting
results since 2006.
In studies concerning MSCs it is also important to consider whether authors
fulfill the three minimal criteria established to define them [
10
]. Ongoing trials will
probably resolve some of these doubts and will try to resolve some other questions
as whether allogeneic or autologous HSCs is better, clarify if the response is owed
to SCs or conditioning treatments, etc. It is also striking that two allogeneic phase
III studies had to be stopped more than a year due to methodological concerns.
Authors commented that there were no safety concerns but right after resuming
enrollment, another trial to study reinfusions (with dose augmentation) and with
much more safety and security evaluation issues was registered, so it seems better
to wait all trials' results.
Special consideration should be given to the unresolved issue of SCs carcino-
genesis. There are some reports of MSCs malignant transformation after prolonged
in vitro culture [
89
,
90
], but some authors have now attributed transformation to
cross-contamination with tumor cells [
91
,
92
] and other studies do not find that
phenomenon [
93
]. Furthermore, this issue has not been observed in vivo and
another study relates SCs fusion with ''pre-malignant'' cells with carcinogenesis
[
94
]. More studies are needed to clearly define this potential causal relationship.
Recent studies have investigated ASCs behavior in the presence of tumor cells.
Some have found migration toward the tumor and tumor growth acceleration [
95
,
96
] but also neoplastic cells apoptosis [
97
,
98
]. The real clinical significance of
these findings is unknown. Based on these, some authors have explored the benefit
from this migratory capacity using SCs as a vehicle for cytotoxic drugs [
99
].
In conclusion we think that more animal data on safety, type of SCs to use, best
dosage and therapeutic mechanisms involved are urgently required. Ongoing trials
results and other large randomized controlled trials are necessary before firm
conclusions can be drawn and SCs must only be applied under the strictly regu-
lated clinical trial setting.
12.8.2 Fistulizing Disease
The SC mostly applied in this condition is ASCs.
12.8.2.1 Relevant Published Studies
In 2002, the first autologous ASCs application was done attempting to seal a
recurrent and refractory rectovaginal fistula in a Crohn's disease patient [
100
]. The
