Biomedical Engineering Reference
In-Depth Information
the Transendocardial Autologous Cells (hMSC or hBMC) in Ischemic Heart
Failure Trial (TAC-HFT; ClinicalTrial.gov Identifier: NCT00768066), the Pro-
spective Randomised study Of MSC THErapy in patients Undergoing cardiac
Surgery (PROMETHEUS) trial (ClinicalTrial.gov Identifier: NCT00587990), and
the
Percutaneous
Stem
Cell
Injection
Delivery
Effects
on
Neomyogenesis
(POSEIDON)
pilot
study
(ClinicalTrial.gov
Identifier:
NCT01087996)
[
224
],
among others.
5.3.2.3 Other Cell Type Clinical Trials
Besides the bone marrow, several other sources of stem cells are also being tested
for their therapeutic potential. Phase I clinical studies are being planned/performed
with the use of hUCBC for the treatment of patients with dilated cardiomyopathy
(DCM) and refractory angina. On the other hand, resident cardiac stem cells are
clearly an attractive option for cardiac repair, although a harvesting technique
remains to be perfected and clinical trials for safety and efficacy are still awaited.
The ongoing CArdiosphere-Derived aUtologous Stem CElls to Reverse ventric-
Ular dySfunction (CADUCEUS) study, which is a Phase I study where 30 patients
have been recruited to receive autologous cardiosphere-derived stem cells, will
hopefully answer some of these questions (ClinicalTrials.gov Identifier:
NCT00893360) (reviewed in [
98
]). The adipose tissue is another ideal source for
immediate access to a patient's own stem cells. Two Phase I trials, the APOLLO
Study (ClinicalTrials.gov Identifier: NCT00442806) and PRECISE Study (Clini-
calTrials.gov Identifier: NCT00426868), are now underway to explore the safety,
feasibility and efficacy of the freshly isolated stromal vascular fraction present in
the adipose tissue, in both acute and chronic myocardial ischemia patients,
respectively (reviewed in [
98
,
176
]). Finally, to date, positive results have been
observed in the clinical assays using circulating progenitor cells [
193
] transplanted
into the infarcted myocardium of patients with ischemic heart disease.
5.4 Tissue Engineering
Despite the general benefit that stem cell therapy offers, some important limita-
tions like the low degree of cell engraftment and survival in the heart have been
evidenced in cell therapy. As an average, more than 70 % of the transplanted cells
are lost during the first 48 h, progressively disappearing during the following days
[
230
]. Cell injection implies that a great percentage of cells directly leak through
capillaries [
231
] and also die through anoikis due to the lack of matrix anchorage-
dependent survival signals [
232
]. Furthermore, MI imposes a hypoxic, pro-
inflammatory and/or fibrotic environment that harms the transplanted cells [
233
].
Despite this aspect, a functional improvement has generally been demonstrated
after cell treatment in the settings of AMI, chronic ischemic heart failure and
