Biomedical Engineering Reference
In-Depth Information
TABLE 12.3 Markers of Stem Cell-Derived Cardiomyocyte Differentiation
Cell Type
Differentiation Agent
Markers of Differentiated
Cardiomyocyte
ES cells
ESCs
IGF-1, TGF-
b
a
-Sarcomeric actin, connexin 43, MHC I,
sarcomeric myosin
5
0
-Azacytidine
P19 embryonal
carcinoma line
BMP-2, BMP-4, Bmpr la, Smadl,
GATA-4, Nkx2.5, cardiac troponin I,
desmin
BMC
Bone marrow
(MSCs)
Insulin, ascorbic acid,
dexamethasone
a
-Skeletal actin,
b
-MHC, MLC-2v,
CaV1.2, cardiac troponin I, sarcomeric
tropomyosin, cardiac titin
Cardiac stem cells
CKIT
þ
Lin-
NA
c-kit
þ
isll
þ
NA
Csx/Nkx-2.5, GATA4
5
0
-Azacytidine
oxytocin
Sca-1
þ
cKit-
High telomerase activity, Sca-1
þ
Csx/Nkx-
2.5, GATA4, MEF-2C,
a þ b
-MHC, MLC-2, cardiac-
a
actin
Cardiosphere
cKit
þ
Cardiac troponin I, myosin heavy chain,
atrial natriuretic peptide
SP cells
NA
ATP-binding cassette transporter (ABCG2)
NA, not available.
Source: Adapted from Ref. [17].
injected into uninjured hearts. In these studies, the injected cells behaved as a
biological pacemaker and electrically excited the rest of the ventricle.
7,53
Problems
are large-scale generation of ESC-derived cardiomyocytes, immunologic rejection,
differentiation into undesirable lineages, and ethical concerns.
12.1.6 Recommendations
The therapeutic use of ESC transplantation in cardiac diseases primarily needs a
rigorous demonstration that it can work in a stable fashion and with limited adverse
effects.
Despite the limitations on federally funded research presently imposed, new
sources of ESCs and cell lines for ESC transplantation studies need to be developed
and likely will be, given the strong worldwide corporate- and state-funded interest in
this technology and its purported benefits. Investigation into novel ways to isolate
and culture autologous ESCs should also prove to be of significance.
Our overall understanding of the factors that may elicit the homing of ESCs to the
heart and stimulate or direct the differentiation of ESCs to functional cardiomyocytes
is presently rudimentary (a critique also applicable to adult stem cells). Identification
of these factors and their mechanism of action will likely optimize both the homing
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