A mouse model for the study of transplanted bone marrow mesenchymal stem cell survival and proliferation in lumbar spinal fusion

Eur Spine J. 2019 Apr;28(4):710-718. doi: 10.1007/s00586-018-5839-y. Epub 2018 Dec 3.

Abstract

Purpose: Bone marrow aspirate has been successfully used alongside a variety of grafting materials to clinically augment spinal fusion. However, little is known about the fate of these transplanted cells. Herein, we develop a novel murine model for the in vivo monitoring of implanted bone marrow cells (BMCs) following spinal fusion.

Methods: A clinical-grade scaffold was implanted into immune-intact mice undergoing spinal fusion with or without freshly isolated BMCs from either transgenic mice which constitutively express the firefly luciferase gene or syngeneic controls. The in vivo survival, distribution and proliferation of these luciferase-expressing cells was monitored via bioluminescence imaging over a period of 8 weeks and confirmed via immunohistochemistry. MicroCT imaging was performed 8 weeks to assess fusion.

Results: Bioluminescence imaging indicated transplanted cell survival and proliferation over the first 2 weeks, followed by a decrease in cell numbers, with transplanted cell survival still evident at the end of the study. New bone formation and increased fusion mass volume were observed in mice implanted with cell-seeded scaffolds.

Conclusions: By enabling the tracking of transplanted bone marrow-derived cells during spinal fusion in vivo, this mouse model will be integral to developing a deeper understanding of the biological processes underlying spinal fusion in future studies. These slides can be retrieved under Electronic Supplementary Material.

Keywords: Bone marrow; Luciferase; Mesenchymal stem cell; Mouse model; Spinal fusion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Animals
  • Bone Marrow Transplantation / methods
  • Cell Proliferation
  • Cell Survival
  • Disease Models, Animal*
  • Female
  • Lumbar Vertebrae / diagnostic imaging
  • Lumbar Vertebrae / pathology
  • Lumbar Vertebrae / surgery*
  • Luminescent Measurements / methods
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / cytology*
  • Mice, Transgenic
  • Spinal Fusion / methods*
  • Tissue Scaffolds
  • X-Ray Microtomography