Abstract

Stem cells are cells with self-renewal and multiple differentiation direction characters. Variety of studies have shown that stem cells have broad prospects in tissue repair and regenerative medicine. However, some aspects of stem cells in vivo transplantation developed slowly, for instance, distribution, activity, differentiation direction and mechanism, which have restricted the development of stem cell therapy. Thus, exploring novel technologies for tracing stem cell in vivo will play a vital role in solving the above scientific problems. When stem cell are labeled magnetically, we can obtain a noninvasive, safe, sustained and dynamic tracing in vivo by combining with magnetic resonance imaging (MRI). In addition, major factors influencing the efficiency of in vivo trace contain cellular content of magnetic material, the different methods for magnetic labeling and the maintenance of cell activity. Here, we review the recent progresses on different ways for magnetic labeling stem cell, the metabolism of magnetic substances and the impact on cell systematically. For magnetic labeling, one of the major aspects focuses on labelling stem cells with magnetic materials like superparamagnetic iron oxide nanoparticles (SPION). Surface modification of SPION and exerting additional physical field when stem cell incubated with SPION both have enhanced label efficiency, however, it could not reflect the actual cellular activity in vivo which might bring out false-positive results by using this approach. Therefore, the use of reporter gene is developed, which could provide strong tissue contrast after stable transfection. However, whether the transfection alters stem cell properties remains to be proved. In addition, after SPION is uptaken by cells, the labeling efficiency will be decreased by a series intracellular degradation and metabolism, most particles is degraded by lysosomes into iron ions which could not provide effective MRI imaging. On the other hand, the cellular reactive oxygen species (ROS) level will increase substantially through Fenton reaction which has toxic effect on cell activity. Thus, SPION degradation in lysosome shows a huge negative influence on tracing, which could not be ignored. Recent research reveals that cell properties such as migration and differentiation will be altered after labeling with SPION. By analyzing the working principles of existing label technology, we cover a detailed outlook on improving magnetic stem cell labeling. We prospect that two momentous issues should be considered to achieve efficient cell labeling and long-term tracing: Phagocytosis and metabolic pathway. More advanced methods ought to be developed to realize secure, rapid, massive cell label. Meanwhile, regulation of intracellular metabolism pathway is also critical for long-term cell tracing. To some extent, coating materials of SPION that allows particles to escape from lysosomes degradation will allow SPION longtime retention in cell. Moreover, labeling SPION extracellular also attracts our attention and its advantage is that SPION labelled on external of plasma membrane could not only be imaged, but also be escaped from cellular metabolism.

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