Noninvasive in-vivo tracing and imaging of transplanted stem cells for liver regeneration
Cen et al. Stem Cell Research & Therapy
Noninvasive in-vivo tracing and imaging of transplanted stem cells for liver regeneration
Panpan Cen 0
Jiajia Chen 0
Chenxia Hu 0
Linxiao Fan 0
Jie Wang 0
Lanjuan Li 0
0 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, School of Medicine; First Affiliated Hospital; Zhejiang University , Hangzhou 310006 , China
Terminal liver disease is a major cause of death globally. The only ultimate therapeutic approach is orthotopic liver transplant. Because of the innate defects of organ transplantation, stem cell-based therapy has emerged as an effective alternative, based on the capacity of stem cells for multilineage differentiation and their homing to injured sites. However, the disease etiology, cell type, timing of cellular graft, therapeutic dose, delivery route, and choice of endpoints have varied between studies, leading to different, even divergent, results. In-vivo cell imaging could therefore help us better understand the fate and behaviors of stem cells to optimize cell-based therapy for liver regeneration. The primary imaging techniques in preclinical or clinical studies have consisted of optical imaging, magnetic resonance imaging, radionuclide imaging, reporter gene imaging, and Y chromosome-based fluorescence in-situ hybridization imaging. More attention has been focused on developing new or modified imaging methods for longitudinal and high-efficiency tracing. Herein, we provide a descriptive overview of imaging modalities and discuss recent advances in the field of molecular imaging of intrahepatic stem cell grafts.
Stem cells; Stem cell therapy; In-vivo imaging; Labeling; Optical imaging; Radionuclides; Super paramagnetic iron oxide; Reporter genes; Liver regeneration
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Background
Liver dysfunction is a serious healthcare problem
worldwide that can progress to fulminant or chronic
liver failure, and eventually deteriorate into end-stage
liver disease. Currently, the only ultimate therapeutic
approach for these diseases is orthotopic liver
transplant (OLT). Nevertheless, the potential benefits are
extraordinarily hindered by the major characteristics
of organ scarcity, surgical intervention, postoperative
complication, and life-long immunosuppressive
medication, which have urgently facilitated the exploration of
novel strategies to promote hepatic self-rehabilitation
ability and reverse the pernicious process.
Early observations that stem cells derived from
somatic cells, bone marrow, and embryonic cells
exhibit the capacity of multipotential differentiation and
self-renewal in vitro led to the proposal that they
might migrate to the injured sites driven by
environmental triggers and partly substitute the function of
hepatocytes. Thus, over the last several years, stem
cell-based therapy has emerged as a possible
alternative, revolutionizing the treatment of liver
regeneration or enabling patients to buy time before liver
transplantation [1–4]. By homing to damaged tissues,
stem cells contribute to alleviating the liver
dysfunction. However, the potential mechanisms involved are
not yet completely understood. Moreover, the disease
etiology, cell type, timing of cellular graft, therapeutic
dose, delivery route, and choice of endpoints have
varied between study groups, leading to different,
even divergent, treatment outcomes. Optimizing stem
cell-based therapies will therefore require a better
understanding of the cellular viability, biodistribution,
differentiation capacity, and long-term fate after
engraftment, with imaging techniques playing a pivotal
role. Successful implementation of proper cell labeling
enables noninvasive monitoring for the in-vivo tracing
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of cellular biology, and provides some clues for stem
cell therapies.
An ideal imaging technique should most of all be
biocompatible; that is, with low toxicity to both the labeled
cells and the host. Additionally, the imaging technique
should allow the relatively long-term visualization of
infused cells with high temporary and spatial resolution,
and meanwhile be available for histological or functional
analysis. In addition, it is vital that the labeling agent or
marker should be highly specific to original cells, passed
to all progenies, and not transfected to nontarget cells
[5, 6]. To the (...truncated)