In the early stages of osteoarthritis, cartilage destruction is not seen on a regular basis. However, as the disease progresses, joints are exposed to progressive inflammation and damage (1). The use of treatment methods for joint injuries, including drug therapy, orthopedic surgery, and arthroplasty, are costly and do not perfectly repair tissue (2, 3). There are some new technologies and approaches, such as regenerative medicine, to renovate the destruction of articular cartilage, which is commonly caused by trauma and osteoarthritis injuries that are increasingly prevalent, especially in the elderly population (4). Common cell-based treatments include culturing the patient's own cartilage, in which cells are removed from the individual, and then the chondrocyte cell is separated by enzymes and cultured outside the body to increase the number of cases (5, 6). It is then placed on an artificial scaffold and is implanted in the body; the person's own healthy cartilage may also be used as a scaffold. However, adult chondrocytes are unable to reproduce extracellular matrices. Because cartilage tissue damage varies in-depth, physicians consider a variety of treatments depending on the patient's age and level of activity based off of the location and extent of the damage. Stem cell (SC) therapy is a turning point in for the treatment of OA in regenerative medicine (7). The principal objective of regenerative medicine is to repair defectives or aged tissues by preserving their morphology and native function. The subsequent therapeutic strategies in resuscitation medicine are mostly administrated to support the potency of tissues to permanently regenerate, and accordingly rely mainly on techniques based on the application of specific growth factors, biological materials, mature cells, as well as SC or progenitor cells (8). Nowadays, cell-based regenerative medicine therapies (RMT)and their adaptations into clinical applications is the interest of research and they are likely to play an important function in subsequent clinical practices (9). There are significant concerns regarding the adaptations of cell-based RMTs into the clinics, such as tumorigenicity, immunogenicity, and the efficacy of comprehension whether cells are self-healing or their derivatives.
Appropriate animal models are essential to study the safety and efficacy of cell-based RMT by investigating the maintenance and migration of cells at the transplant location (10). In these methods, once destroyed, the animal model and prepared tissue sections can undergo histological analyses in which the number and location of transplanted stem cells in most tissues can be examined (11). Hence, novel techniques have been developed that make their application span a long term with multiple trials in the animal, which enable researchers to evaluate counting and migration, or assess death of the transplanted stem cells.
Advances in cellular imaging technologies make the real-time tracking of transplanted cells in live animals possible. Current procedures commonly rely on tissue analysis, as well as various imaging techniques. The main clinical imaging tools include Single-Photon Emission Tomography (SPECT), Positron Emission Tomography (PET), and Magnetic Resonance Imaging (MRI) (12). There are also multiple methods of optical imaging using Fluorescence Imaging (FI), that are widely applicable in small animal models (13). In addition, many hybrid systems that combine two or more of these methods are already commercially available. Imaging cell tracking methods are non-invasive monitoring methods at the injection site which observe the dissemination and viability of the injected cells (14). The administration of non-invasive and the quantitative imaging of stem cells can simplify preclinical experimental studies in animal models, and may also aid in therapeutic trials of human stem cells. Stem cell therapy with non-invasive imaging can dispense more intuition into, not only therapeutic interest, but also the underlying mechanisms of stem cell fate, migration, survival, and in vivo transplantation. Therefore, in this review, different suggestive sources of stem cells are explained, and the main features of the available non-invasive imaging method for SC tracking are discussed.