Top

Published in:

01-04-2019 | Original Article

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

Authors: 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

Published in: European Spine Journal | Issue 4/2019

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.

Available only for authorised users

Kitchel SH (2006) A preliminary comparative study of radiographic results using mineralized collagen and bone marrow aspirate versus autologous bone in the same patients undergoing posterior lumbar interbody fusion with instrumented posterolateral lumbar fusion. Spine J 6:405–411. https://doi.org/10.1016/j.spinee.2005.09.013 CrossRefPubMed

Neen D, Noyes D, Shaw M et al (2006) Healos and bone marrow aspirate used for lumbar spine fusion: a case controlled study comparing healos with autograft. Spine (Phila Pa 1976) 31:E636–E640. https://doi.org/10.1097/01.brs.0000232028.97590.12 CrossRef

Salamanna F, Sartori M, Brodano GB et al (2017) Mesenchymal stem cells for the treatment of spinal arthrodesis: from preclinical research to clinical scenario. Stem Cells Int 2017:1–27. https://doi.org/10.1155/2017/3537094 CrossRef

Robbins MA, Haudenschild DR, Wegner AM, Klineberg EO (2017) Stem cells in spinal fusion. Glob Spine J 7:801–810. https://doi.org/10.1177/2192568217701102 CrossRef

Grayson WL, Bunnell BA, Martin E et al (2015) Stromal cells and stem cells in clinical bone regeneration. Nat Rev Endocrinol 11:140–150. https://doi.org/10.1038/nrendo.2014.234 CrossRefPubMedPubMedCentral

Undale AH, Westendorf JJ, Yaszemski MJ, Khosla S (2009) Mesenchymal stem cells for bone repair and metabolic bone diseases. Mayo Clin Proc 84:893–902. https://doi.org/10.1016/S0025-6196(11)60506-5 CrossRefPubMedPubMedCentral

Šponer P, Kučera T, Diaz-Garcia D, Filip S (2014) The role of mesenchymal stem cells in bone repair and regeneration. Eur J Orthop Surg Traumatol 24:257–262. https://doi.org/10.1007/s00590-013-1328-5 CrossRefPubMed

Bobyn J, Rasch A, Little DG, Schindeler A (2013) Posterolateral inter-transverse lumbar fusion in a mouse model. J Orthop Surg Res 8:2. https://doi.org/10.1186/1749-799X-8-2 CrossRefPubMedPubMedCentral

Rao RD, Bagaria VB, Cooley BC (2007) Posterolateral intertransverse lumbar fusion in a mouse model: surgical anatomy and operative technique. Spine J 7:61–67. https://doi.org/10.1016/j.spinee.2006.03.004 CrossRefPubMed

10.

Kolind M, Bobyn JD, Matthews BG et al (2015) Lineage tracking of mesenchymal and endothelial progenitors in BMP-induced bone formation. Bone 81:53–59. https://doi.org/10.1016/j.bone.2015.06.023 CrossRefPubMedPubMedCentral

11.

Cao Y-A, Wagers AJ, Beilhack A et al (2004) Shifting foci of hematopoiesis during reconstitution from single stem cells. Proc Natl Acad Sci USA 101:221–226. https://doi.org/10.1073/pnas.2637010100 CrossRefPubMed

12.

Cao Y-A, Bachmann MH, Beilhack A et al (2005) Molecular imaging using labeled donor tissues reveals patterns of engraftment, rejection, and survival in transplantation. Transplantation 80:134–139CrossRefPubMed

13.

Sheikh AY, Lin S-A, Cao F et al (2007) Molecular imaging of bone marrow mononuclear cell homing and engraftment in ischemic myocardium. Stem Cells 25:2677–2684. https://doi.org/10.1634/stemcells.2007-0041 CrossRefPubMedPubMedCentral

14.

Lina IA, Puvanesarajah V, Liauw JA et al (2014) Quantitative study of parathyroid hormone (1-34) and bone morphogenetic protein-2 on spinal fusion outcomes in a rabbit model of lumbar dorsolateral intertransverse process arthrodesis. Spine (Phila Pa 1976) 39:347–355. https://doi.org/10.1097/brs.0000000000000169 CrossRef

15.

Qiao H, Zhang R, Gao L et al (2016) Molecular imaging for comparison of different growth factors on bone marrow-derived mesenchymal stromal cells’ survival and proliferation in vivo. Biomed Res Int 2016:1–10. https://doi.org/10.1155/2016/1363902 CrossRef

16.

Huang S, Xu L, Sun Y et al (2015) The fate of systemically administrated allogeneic mesenchymal stem cells in mouse femoral fracture healing. Stem Cell Res Ther 6:206. https://doi.org/10.1186/s13287-015-0198-7 CrossRefPubMedPubMedCentral

17.

Geuze RE, Prins H-J, Öner FC et al (2010) Luciferase labeling for multipotent stromal cell tracking in spinal fusion versus ectopic bone tissue engineering in mice and rats. Tissue Eng Part A 16:3343–3351. https://doi.org/10.1089/ten.TEA.2009.0774 CrossRefPubMed

18.

Welsh DK, Kay SA (2005) Bioluminescence imaging in living organisms. Curr Opin Biotechnol 16:73–78. https://doi.org/10.1016/j.copbio.2004.12.006 CrossRefPubMed

19.

Kim JE, Kalimuthu S, Ahn B-C (2015) In vivo cell tracking with bioluminescence imaging. Nucl Med Mol Imaging (2010) 49:3–10. https://doi.org/10.1007/s13139-014-0309-x CrossRef

20.

Manassero M, Paquet J, Deschepper M et al (2016) Comparison of survival and osteogenic ability of human mesenchymal stem cells in orthotopic and ectopic sites in mice. Tissue Eng Part A 22:534–544. https://doi.org/10.1089/ten.tea.2015.0346 CrossRefPubMed

21.

Todeschi MR, El Backly R, Capelli C et al (2015) Transplanted umbilical cord mesenchymal stem cells modify the in vivo microenvironment enhancing angiogenesis and leading to bone regeneration. Stem Cells Dev 24:1570–1581. https://doi.org/10.1089/scd.2014.0490 CrossRefPubMedPubMedCentral

Title: A mouse model for the study of transplanted bone marrow mesenchymal stem cell survival and proliferation in lumbar spinal fusion
Authors: 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
Publication date: 01-04-2019
Publisher: Springer Berlin Heidelberg
Published in: European Spine Journal / Issue 4/2019
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI: https://doi.org/10.1007/s00586-018-5839-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusions

Graphical abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Graphical abstract

Please log in to get access to this content

Other articles of this Issue 4/2019

Failure to maintain segmental lordosis during TLIF for one-level degenerative spondylolisthesis negatively affects clinical outcome 5 years postoperatively: a prospective cohort of 57 patients

Sonication of removed implants improves microbiological diagnosis of postoperative spinal infections

Correction to: The “Risser+” grade: a new grading system to classify skeletal maturity in idiopathic scoliosis

Identification of abnormalities in the lumbar nerve tract using diffusion-weighted magnetic resonance neurography

Expert’s comment concerning Grand Rounds case entitled “Retroperitoneal haematoma in a postoperative ALIF patient taking rivaroxaban for atrial fibrillation” by Deekonda P, Stokes OM, Chan D (Eur Spine J [2016]: DOI 10.1007/s00586-016-4822-8)

Triangular titanium implants for sacroiliac joint fusion