Lost signature: progress and failures in in vivo tracking of implanted stem cells

Abstract

Stem cell therapy as a part of regenerative medicine provides promising approaches for the treatment of injuries and diseases. The increasing use of mesenchymal stem cells in various medical treatments created the demand for long-term in vivo cell tracking methods. Therefore, it is necessary to analyze post-transplantational survival, biodistribution, and engraftment of cells. Furthermore, stem cell treatment has been discussed controversially due to possible association with tumor formation in the recipient. For therapeutic purpose, stem cells must undergo substantial manipulation such as differentiation and in vitro expansion, and this can lead to the occurrence of genetic aberrations and altered expression of both tumor suppression and carcinogenic factors. To control therapy, it is necessary to find a reliable and general method to track and identify implanted cells in the recipient. This is especially challenging for autologous transplantations, as standard fingerprinting methods cannot be applied. An optimal technique for in vivo cell monitoring does not yet exist, and its development holds several challenges: small numbers of transplanted cells, possibility of cell number quantification, minimal transfer of the contrast agent to non-transplanted cells, and no genetic modification. This review discusses most of the proposed solutions, including magnetic resonance imaging, magnetic particle imaging, positron emission tomography, single-photon emission computed tomography, and optical imaging methods. Additionally, the recent research on cell labeling for stem cell monitoring after transplantation including in vitro, ex vivo, and in vivo imaging studies is described. Promising future imaging modalities for stem cell monitoring after transplantation are shown.

Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

“…Imaging tools to follow the fate of implanted cells, to localize them and more importantly to quantify them, are available or under rapid development. 254 The interplay between exogenous and resident cells is another poorly explored question, and the rich secretome of MSCs certainly plays a major role in the recruitment, maturation, and organization of the resident cells within the regenerating tissue. A better knowledge of cell behavior on transplantation will be pivotal in drawing guidelines for the design of hydrogel-based systems with mechanical, structural, and biological properties optimized for osteogenesis.…”

Accomplishments and challenges in stem cell imaging in vivo

“…The importance of half-life in direct SC labeling is that it limits the temporal window to label, administer and track cells as they home and accumulate in their target tissue. By contrast, SPECT radiotracers such as indium-111 ( 111 In) or metastable technicium-99m ( 99 mTc) emit gamma rays that are detected by a rotating gamma camera [35,36]. Compared with PET, SPECT has a lesser spatial resolution, and the lower gamma energy is more attenuated in the body; however, the half-life of its radiotracers: hours to days, is more favorable for SC labeling and tracking [17,36].…”

Molecular Imaging of Stem Cell Transplantation for Liver Diseases: Monitoring, Clinical Translation, and Theranostics

“…For promoting therapeutic effect, stem cells may undergo substantial manipulation such as differentiation and in vitro expansion, and this can lead to possible genetic aberrations and carcinogenesis [71]. To address the intractable issues such as the teratoma formation encountered in human embryonic stem cell (hESC) for therapeutic in clinic, Chung et al hypothesized that serial manganese-enhanced MRI would have theranostic effect to assess hESC survival, teratoma formation, and hESC-derived teratoma reduction through intracellular accumulation of Mn2+.…”

“…The increasing application of stem cells transplantation for liver diseases treatments created the demand for long-term and quantitative in vivo cell tracking methods [71]. In this review, promising in vivo imaging methods for stem cell monitoring after transplantation in liver are shown.…”