Abstract

Cellular transplantation strategies utilizing intraspinal injection of mesenchymal progenitor cells have been reported as beneficial for spinal cord injuries. However, intraspinal injection is not only technically challenging, but requires invasive surgical procedures for patients. Therefore, we investigated the feasibility and potential benefits of non-invasive intravenous injection of mesenchymal progenitor cells in two models of cervical spinal cord injury, unilateral C5 contusion and complete unilateral C5 hemisection. Mesenchymal progenitor cells were isolated from GFP-luciferase transgenic mice compact bone (1x10(6) cells) or vehicle (HBSS) were intravenously injected via the tail vein at D1, D3, D7, D10 or D14. Transplanted mesenchymal progenitor cells were tracked via bioluminescence imaging. Live in vivo imaging data showed that intravenously injected mesenchymal progenitor cells accumulate in the lungs, confirmed by post-mortem bioluminescence signal - irrespective of the time of injection or injury model. The results showed a rapid, positive modulation of the inflammatory response providing protection to the injured spinal cord tissue. Histological processing of the lungs showed GFP(+) cells evenly distributed around the alveoli. We propose that injected cells can act as cellular target decoys to an immune system primed by injury, thereby lessening the inflammatory response at the injury site. We also propose that intravenous injected mesenchymal progenitor cells modulate the immune system via the lungs through secreted immune mediators or contact interaction with peripheral organs. In conclusion, the timing of intravenous injection of mesenchymal progenitor cells is key to the success for improving function and tissue preservation following cervical spinal cord injury. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/stem.2364

View details for Web of Science ID 000379902900009

View details for PubMedID 26989838