Trafficking the fate of mesenchymal stem cells in vivo

Abstract

106

Objectives: To track the distribution and differentiation of mesenchymal stem cells (MSCs) in tumor-bearing mice.

Methods: The murine breast cancer 4T1 cells and MSCs were labeled with rLuc-mRFP and fLuc-eGFP reporter gene, respectively. Two tumor models were established by injecting the 4T1-rLuc-mRFP cells intravenously or subcutaneously. Animals were divided into 3 groups and received MSC-Fluc-eGFP cells injection 4 days after 4T1-rLuc-mRFP i.v. injection, 1 week after subcutaneous inoculation of 4T1-rLuc-mRFP cells, or normal mice without tumors. The tumor growth was monitored by rLuc BLI. The fate of MSC-Fluc-eGFP cells was monitored by fLuc BLI. The co-localization of MSC-Fluc-eGFP and 4T1-rLuc-mRFP cells was examined by ex vivo fluorescence microscope. The osteogenic and adipogenic differentiation of MSC-Fluc-eGFP was investigated by Alizarin Red S and oil red staining respectively. The mechanism underlying the different differentiation propensity of MSCs in different tissue was investigated.

Results: When injected intravenously, MSCs were trapped in the lung during the first 2 days in all groups, which were then survived, proliferated and differentiated only in tumor site as shown in Fig. 1. The colocalization of RFP+ tumor cells and GFP+ MSCs were further confirmed by ex vivo fluorescence examination. Interestingly, the MSCs homing to lung 4T1 tumor differentiated into osteoblast cells whereas the MSCs homing to subcutaneous 4T1 tumor differentiated into adipocytes. The possible cause of different differentiation might be that BMPs are abundant in lung.

Conclusions: MSCs can home to both subcutaneous breast cancer and its lung metastasis. The fate of MSCs after homing to lung tumor or s.c. tumor are distinctly different due to the different protein expression pattern in these two organs.