Noninvasive in-vivo tracing and imaging of transplanted stem cells for liver regeneration

Stem Cell Research & Therapy, Sep 2016

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.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

https://link.springer.com/content/pdf/10.1186%2Fs13287-016-0396-y.pdf

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 - 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 © 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. 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)


This is a preview of a remote PDF: https://link.springer.com/content/pdf/10.1186%2Fs13287-016-0396-y.pdf

Panpan Cen, Jiajia Chen, Chenxia Hu, Linxiao Fan, Jie Wang, Lanjuan Li. Noninvasive in-vivo tracing and imaging of transplanted stem cells for liver regeneration, Stem Cell Research & Therapy, 2016, pp. 143, Volume 7, Issue 1, DOI: 10.1186/s13287-016-0396-y