Stem cells, as a class of self-renewing pluripotent cells, can differentiate into diverse types of cells with different functions under appropriate conditions.[1-4] There are two major types of stem cells, embryonic stem cells (ESCs) and adult stem cells.[5, 6] While ESCs are usually isolated from the inner cell mass of blastocysts,[4, 6, 7] adult stem cells can be found in various tissues such as bone marrow, adipose tissues, and blood (e.g., umbilical cord blood).[8-11] In recent years, stem cells have shown great potential in a number of different biomedical applications and their research has become an extremely exciting area that has received tremendous attention. It is believed that stem cell transplantation technology could be a historic breakthrough, and it offers great promise for the treatment of many diseases.[3, 12, 13] Transplantation of ESCs has demonstrated advantages in the treatment of Parkinson's, liver failure, and diabetes.[14-17] Compared with ESCs, which have moral controversy, adult stem cells are easily accepted by the public and have been routinely used in medical therapies. For example, the hematopoietic stem cells (bone marrow) transplantation could be used to treat a wide range of diseases including multiple myeloma, leukemia, lymphoma, and Hodgkin's disease.[15, 18-20] Transplantation of neural stem cells, on the other hand, may treat diseases of nervous systems, such as Huntington's disease, stroke, cerebral palsy, spinal cord injury, and cerebral hemorrhage.[21-23] Mesenchymal stem cells (MSCs) transplantation is also a potential effective therapeutic approach to treat diseases including wound healing, ischemic encephalopathy, and ischemic heart disease.[24-26] Stem cells therapy could overcome many limitations in tissue or organ transplantation, such as donor shortage and donor site morbidity, pathogen transmission, and immune incompatibility.[27-29]
Although stem cells hold great potential in medical applications, before their therapeutic applications can be realized, scientists and clinicians must develop advanced techniques to understand the fate, distribution, and functions of transplanted stem cells in the local microenvironment, and to effectively control the behavior of transplanted stem cells. Therefore, it is necessary to develop accurate and reliable methods to label stem cells and to use imaging techniques to track their translocation after transplantation. The current methods to label and track stem cells can be generally divided into two major classes, gene modifications and external labels. Common gene modifications of stem cells for tracking usually rely on fluorescent proteins (e.g., green fluorescence protein (GFP)) and luciferase, whose genes could be expressed inside appropriately transfected cells.[30-33] The method to label and track stem cells by gene modification is beneficial for long-term tracking as long as the introduced labeling genes are stable in stem cells and can be constantly passed into their daughter generations. However, gene-modified stem cells expressing fluorescence proteins or luciferase can only be detected by optical imaging, which has limited tissue penetration and thus is only applicable for small animal imaging.[34-36] In addition, there have been concerns that the induced foreign genes may change the behavior and functions of stem cells.
The other type of method to label and track stem cells uses external labels, many of which are nanomaterials with unique physical features (e.g., interesting optical and magnetic properties) that can be internalized by stem cells and utilized as probes in biomedical imaging.[38-41] In the past decade, the development of nanoparticles for stem cell labeling and tracking has been widely explored, showing numerous encouraging results in many preclinical animal experiments as well as in some clinical trials.[42-44] Here, we summarize and discuss the use of nanoparticles for stem cell labeling and in vivo tracking, with particular attention paid to several commonly studied types including magnetic nanoparticles, photoluminescent nanoparticles, and several other classes of nanoparticles such as carbon nanotubes (CNTs) and composite nanoparticles (Table 1). Magnetic nanoparticles have been extensively used for stem cell labeling, allowing whole body in vivo tracking by magnetic resonance (MR) imaging. Photoluminescent nanoparticles, including traditional fluorescent nanoparticles such as quantum dots (QDs), as well as recently developed upconversion nanoparticles (UCNPs), are useful imaging probes for stem cell labeling and tracking in small animals. Moreover, a number of other types of nanomaterials, such as CNTs and composite multifunctional nanoparticles (MFNPs), have also shown promise in stem cell tracking by multimodal imaging.[44-48] Despite promising results presented in many different reports, there are still a few major challenges of using nanoparticles in stem cell labeling and tracking.[39, 49, 50] This review article provides an overview of using nanoparticles for stem cell labeling and in vivo tracking, in addition to the pros and cons of each labeling and imaging technique.