CT/Bioluminescence Dual-Modal Imaging Tracking of Mesenchymal Stem Cells in Pulmonary Fibrosis

Human mesenchymal stem cells (hMSCs), due to their immune regulation and collateral secretion effects, are currently being explored for potential therapy of idiopathic pulmonary fibrosis (IPF). Understanding the migration, homing, functions, as well as survival of transplanted hMSCs is critical to the successful IPF treatment. To obtain such information, development of relaible, nonincasive and real-time imaging technologies are highly desired.

Recently, a research team led by Prof. Zhang Zhijun from Suzhou Institute of Nano-Tech and Nano-Bionics (SINANO), Chinese Academy of Sciences(CAS), developed a dual-labeling strategy by integrating gold nanoparticle (AuNP)-based CT nanotracer and red-emitting firefly luciferase (RfLuc)-based bioluminescence (BL) tag for CT/BL multimodal imaging tracking of the transplanted human MSCs (hMSCs) in a murine model of IPF. The novel Au@TAT nanotracer coated by PEG and TAT exhibited favorable biocompatibility, remarkable labeling efficiency, and enhanced CT contrast, without noticeable adverse effects on the viability, proliferation and differentiation of the hMSCs. In addition, the optical imaging based on RfLuc could simultaneously increase the detection sensitivity and identify the living cells in vivo. By corecording the CT and BLI signals from the transplanted hMSCs of the same mouse, the survival, location and distribution of the transplanted hMSCs were investigated simultaneously, thereby facilitating the profound understanding of the mechanism of the transplanted stem cells in PF treatment.

The current work represents a general, facile, and versatile strategy for multimodal imaging tracking of stem cells in vitro and in vivo, which may furhter advance the stem cell-based therapeutics and regenerative medicine.

This work was financially supported by the National Key R&D Program of China, National Natural Science Foundation of China，and Jiangsu Provincial Fund for Natural Sciences.

Hongying Bao, Yuyang Xia, Chenggong Yu, Xinyu Ning, Xiaoyun Liu, Han Fu, Zhongjin Chen, Jie Huang,* and Zhijun Zhang*. CT/Bioluminescence Dual-Modal Imaging Tracking of Mesenchymal Stem Cells in Pulmonary Fibrosis. Small, Sept, 29, 2019. DOI: 10.1002/smll.201904314.

Scheme 1. Schematic illustration of the dual-labeling CT/BLI strategy that combines the exogenous Au@TAT nanotracers and the endogenous RfLuc for tracking of the transplanted hMSCs via intratracheal (i.t.) administration in BLM-induced PF. (Image by SINANO)