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

  • Ioan A. Lina
  • Wataru Ishida
  • Jason A. Liauw
  • Sheng-fu L. Lo
  • Benjamin D. Elder
  • Alexander Perdomo-Pantoja
  • Debebe Theodros
  • Timothy F. Witham
  • Christina Holmes
Original Article

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.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

Keywords

Spinal fusion Mouse model Bone marrow Luciferase Mesenchymal stem cell 

Notes

Funding

Work in the Spinal Fusion Laboratory is supported by The Gordon and Marilyn Macklin Foundation and the AO Foundation (Grant No. S-16-59H).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

586_2018_5839_MOESM1_ESM.pptx (674 kb)
Supplementary material 1 (PPTX 673 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Ioan A. Lina
    • 1
  • Wataru Ishida
    • 2
  • Jason A. Liauw
    • 2
  • Sheng-fu L. Lo
    • 2
  • Benjamin D. Elder
    • 3
  • Alexander Perdomo-Pantoja
    • 2
  • Debebe Theodros
    • 2
  • Timothy F. Witham
    • 2
  • Christina Holmes
    • 2
  1. 1.Department of OtolaryngologyThe Johns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of NeurosurgeryThe Johns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Department of Neurological SurgeryMayo Clinic School of MedicineRochesterUSA

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