TITLE: Ultrasound guided photoacoustic monitoring of mesenchymal stem cells for tissue
regeneration
AUTHORS: Seung Yun Nam
INSTITUTIONS: Biomedical Engineering, Pukyong National University, Busan, Korea.
ABSTRACT: Stem cell therapy is a promising candidate for the novel alternative treatment of
ischemic cardiovascular diseases. Medical imaging has an important role in stem cell therapy
because stem cell behaviors and tissue regeneration indicators (e.g., neovascularization) need to
be monitored for effective therapy following stem cell implantation. However, current imaging
techniques for stem cell therapy using various contrast agents suffer from significant limitations
such as short imaging duration (PET/SPECT), low cell detection sensitivity (MRI), and shallow
penetration depth (optical microscopy). Ultrasound guided photoacoustic (US/PA) imaging has a
great potential to overcome drawbacks of other stem cell imaging methods because it can
achieve noninvasiveness with spatial resolution on the order of micrometers and great
sensitivity/selectivity with
various endogenous and exogenous contrast agents
including
hemoglobin and metallic nanoparticles. Therefore, we demonstrated that US/PA imaging is
capable of longitudinal in vivo monitoring of migration of mesenchymal stem cells (MSCs) labeled
with gold nanoparticles (AuNPs) and feasible of tracking the interaction of vascular growth with
tissue regeneration (panel a).
To verify longitudinal in vivo monitoring of stem cell distribution,
the AuNP labeled MSCs (1×105 cells/mL, 3×104 cells) were injected intramuscularly in the hind
limb of the Lewis rat and imaged at a range of wavelengths from 650 nm to 920 nm using a high
frequency US/PA imaging system. The ultrasound image shows morphology of the lower limb, and
the photoacoustic image represent various optical absorbers in the tissue which were
distinguished as AuNP labeled MSCs (green), oxygenated (red) and deoxygenated hemoglobin
(blue), and skin (yellow) by spectral analysis due to each unique optical absorbance (panel b). The
3D combined ultrasound and spectroscopic image shows not only distribution of MSCs but also
microvasculature in the rat lower limb (panel c). After stem cell implantation, the AuNP labeled
MSCs were able to be tracked for up to 10 days with a strong signal using US/PA imaging
(Supporting Information). Based on quantitative analysis, the AuNP labeled MSCs can be imaged
more than 10 days because of the excellent cell detection sensitivity of US/PA imaging. These
results indicate that US/PA imaging has the capability of long-term noninvasive monitoring of
stem cell migration and it also has a great potential to detect neovascularization if it is applied to
ischemic muscle injury cases with high resolution and sensitivity.
Ultrasound / Photoacoustic
US/PA
imaging
probe
Implanted
hydrogel with
AuNP labeled 2 mm
MSCs
Ultrasound / Spectroscopic
Muscle
(a)
(b)
(c)