移植干细胞死活活体示踪技术研究进展

Progress of tracking the viability of transplanted stem cells in vivo

近年来,干细胞再生医学作为未来治愈人类重大疾病最具潜力的方法之一,吸引了科学工作者的广泛关注.清晰了解移植干细胞在活体中的存活、迁移和分化行为是指导干细胞有效治疗的重要前提,其中移植干细胞在体内的存活率更是决定干细胞疗法成败的关键因素.因此,发展有效示踪干细胞死活的影像技术以有效评估干细胞在活体的存活,已成为当今的一大研究热点.本文就目前干细胞死活示踪活体影像技术的研究进展予以综述和展望.

In the last decades, stem cell-based regenerative medicine has attracted intense attention and extraordinary expectation due to its potentials in the treatment of numerous major diseases, such as hepatic, cardiac, pulmonary, renal and neurological diseases. Clearly knowing the viability, distribution and differentiation of the transplanted stem cells in vivo is a prerequisite for better understanding the role of stem cells playing in the therapeutic process, in which the survival report of the transplanted stem cells in vivo is particularly crucial in determining the success of stem cell-based regenerative medicine. Therefore, the development of non-invasive imaging methods that can in situ monitor the viability of the transplanted stem cells is urgently needed. In this review, we summarize the recent progress in tracking the viability of the transplanted stem cells in vivo, including reporter-gene based methods, exogenous contrast label-based methods and multimodel imaging methods. The reporter-gene based methods rely on functional proteins that produce only in live cells, thus the imaging signals are specifically coresponding to the viability of cells. Reporter gene-based imagings, including the luciferase-based bioluminescence imaging（BLI）, ferritin-based magnetic resonance imaging（MRI） and thymidine kinase-based positron emission computed tomography（PET） have been the most robust technique for short- and long-term monitoring cell viability in vivo. Herein, we explain basic principles of these reporter gene-based methods, and describe current examples and future prospects of these methods. In contrast to reporter-gene based methods, methods using exogenous contrast labels such as quantum dots and superparamgnetic iron oxides give a strong signal in cell tracking, but they cannot assess cell survival or death for the agents continue to display signals when the transplanted stem cells are dying. More recently, new nanotechnologies using exogenous contrast labels were developed to monitor cell viability in vivo, such as the p H-nanosensor-based MRI method, the dual-contrast MRI method and the fluorescence imaging method using self-illuminating nano-probes. In this review, the imaging principles underlying these techniques are explained, and the recent examples of exogenous contrast label-based methods are described. Multimodel imaging that combines the reportergene-based technique and exogenous labeling method, such as the combined MRI/PET method, PET/BLI method, MRI/BLI method, or fluorescence imaging/BLI method, has been proposed to in vivo monitor both cell death and cell viability. This review summarizes the recent development of multimodel imaging methods, emphasizes the promise of the combined NIR-II fluorescence imaging/BLI method and MRI/PET method for in vivo tracking cell viability, and discusses the current challenges of multimodel imaging. In conclusion, this review provides an overview of the current imaging methodologies for cell viability tracking, and discusses the current challenges and further prospects of cell viability imaging methods.