Use small molecule protein complexes to label stem cells to achieve high spatiotemporal resolution in vivo tracing

Stem cell therapy has been used in clinical trials for the treatment of skin injuries, blood and cardiovascular diseases, cartilage defects, diabetes and other diseases
.

However, due to the complexity of stem cell therapy, its efficacy and safety have always been questioned

At present, the commonly used PET-CT and MRI imaging for stem cell tracking have disadvantages such as expensive, limited temporal and spatial resolution, and low throughput
.

In recent years, fluorescence imaging in the near-infrared zone (NIR-II, 1000-1700 nm, penetration depth of the living body ~1cm) in vivo has provided new ideas for cell tracing

Recently, Cheng Zhen and Chen Hao’s team from the Molecular Imaging Center of Shanghai Institute of Materia Medica, Chinese Academy of Sciences collaborated with the research group of Associate Professor Li Kai from Southern University of Science and Technology to design a stem cell tracer (CelTrac1000) based on the NIR-II small molecule dye protein complex.
To mark and trace the response and fate of stem cells in different disease environments
.

CelTrac1000 uses metabolizable NIR-II small molecule dye (CH-4T) and human serum albumin (HSA) modified with penetrating peptide (Tat) in a 1:1 compound, and its shape is similar to the marketed drug paclitaxel albumin (Abraxane, etc.

Figure 1.
Schematic diagram of the preparation process and structure of CelTrac1000

The team used this probe to visualize the angiogenesis in human induced pluripotent stem cells-derived endothelial cells (iPSC-ECs) within 1 month, and evaluated the therapeutic effect of iPSC-ECs transplantation regeneration
.

In order to verify the temporal and spatial resolution of this method, the researchers used CelTrac1000 to label mouse mesenchymal stem cells (MSC) for dynamic tracking in vivo, and clearly saw the real-time migration process of the labeled MSC in the blood circulatory system

Finally, the researchers used CelTrac1000 to achieve MSC tracing in three disease models-acute lung injury (ALI), myocardial infarction (MI) and middle cerebral artery occlusion (MCAO) (Figure 2)
.

Because MSCs tend to be enriched in tissues at the injured site, using CelTrac1000 to label cells can observe the biodistribution of MSCs injected into the tail vein in diseased mice

In summary, this study shows that CelTrac1000 can be used to label stem cells and achieve NIR-II high spatio-temporal resolution in vivo tracing, which provides assistance in revealing the pharmacokinetic mechanism of stem cells in vivo
.

Figure 2.
MSC traces in acute lung injury (ALI), myocardial infarction (MI) and middle cerebral artery occlusion (MCAO)

　　Researcher Chen Hao from the Molecular Imaging Center of Shanghai Institute of Materia Medica is the first author of this study.
Associate Professor Li Kai from Southern University of Science and Technology and Researcher Cheng Zhen from the Molecular Imaging Center of Shanghai Institute of Materia Medica are the corresponding authors
.

The research was funded by the National Natural Science Foundation of China, Shanghai Pujiang Talents, and Shanghai Science and Technology Major Projects

　　Full text link: https://spj.

　　(Contributor: Chen Hao's research group; Contributor: Wang Zhiming)