Biomedical Engineering Reference
In-Depth Information
groups but silica coating significantly reduced nephrotoxicity [119]. Han
et al
. reported a
concentration-dependent cell apoptosis, G1 cell-cycle arrest, and increased level of oxidative
stress in glioma cells after exposure to untreated multiwalled carbon nanotubes, with smaller
tubes (10-20 nm) being more toxic than the larger tubes (40-100 nm) [120]. Taken together,
toxicity results demonstrate that gold NPs or other NPs with a gold shell coated with PEG
have the lowest toxicity among different NP types. Coated and uncoated polymeric NPs pre-
pared with poly(lactide-co-glycolide) and its copolymers with PEG exhibit low inflammatory
response [121].
Nanoparticles for Detecting Stem Cells
Safe and reliable use of stem cells in regenerative medicine requires monitoring and
controlling the differentiation of stem cells to a specified lineage. In that regard, NPs are very
attractive for nondestructive detection, imaging, and monitoring of stem-cell differentiation
[122-126]. Surface enhanced Raman spectroscopy (SERS) is an optical technique for the
analysis of the molecular fingerprint of a sample without exogenous labeling, including
molecular bonds, conformations, and intermolecular interactions [87]. Embryonic stem cells
(ESCs) secrete specific DNA, mRNA, and proteins as they differentiate toward a specific
lineage, with significant biochemical differences between the undifferentiated and differenti-
ated states. Sathuluri
et al
. used gold NPs as optical scattering agents, SERS, and global
differences in chemical content to distinguish between ESCs, embryoid bodies (EBs), and
EB-differentiated cardiomyocytes [87]. The molecular signatures included DNA/RNA
content (oxygen-phosphorous-oxygen (OPO) scattering peaks), protein translation activ-
ities (amide scattering peaks), and mitochondria (ATP and glucose oxidation scattering
peaks). The undifferentiated single ESCs were identified by a high content of DNA/RNA
scattering peaks; the EBs by a high content of protein translation scattering peaks; and dif-
ferentiated cardiomyocytes by a high content of scattering peaks related to mitochondria
activity [87]. The SERS studies indicated that EBs are the early stage embryonic differentiation,
not simply an aggregate of ESCs, with significantly higher protein translation activity than
the ESCs [87]. Kim
et al
. developed graphene oxide encapsulated gold NPs for detection of
differentiation of neural stem cells (NSCs) with SERS (Figure 9.2A). Due to the presence of
polyunsaturated fatty acids, such as arachidonic acid, eicosa pentaenoic acid, and hexanoic
acid in their cell membrane, undifferentiated NSCs show a strong C=C Raman band cen-
tered at 1656 cm
−1
on graphene oxide encapsulated gold NPs, while the differentiated neural
cells exhibit a low intensity Raman signal [122]. Since undifferentiated stem cells are rich in
unsaturated structures, these gold NPs may be useful for
in situ
monitoring of the
differentiation state of various types of stem cells, including embryonic, mesenchymal,
hematopoietic, and neural stem cells [127].
Superparamagnetic iron oxide (SPIONs) NPs are used in magnetic resonance imaging
(MRI) as a contrast agent for tracking stem cells after
in vivo
transplantation [128]. Zeng
et al
. investigated the cytotoxic effect of encapsulated SPIONs on neural differentiation of
human amniotic-derived mesenchymal stem cells (hAM-dMSCs) in single and multiple
labeling (Figure 9.2B) [124]. They reported that single SPION-labeling was safe for moni-
toring the
in vivo
transplanted cells and did not affect viability and neural differentiation of
hAM-dMSCs [124]. Superparamagnetic iron oxides are also potentially useful for tracking
migration of ESCs to determine the fate of transplanted cells
in vivo
by cardiac magnetic
resonance for treating myocardial infarction [126]. Au
et al
. reported that SPION labeling
did not affect cardiac capacity, cellular calcium flux, and differentiation potential of ESCs,
and that cardiac MRI could track the labeled cells
in vivo
[126]. Furthermore, direct injection
