Ioan A Lina1, Wataru Ishida2, Jason A Liauw2, Sheng-Fu L Lo2, Benjamin D Elder3, Alexander Perdomo-Pantoja2, Debebe Theodros2, Timothy F Witham2, Christina Holmes4. 1. Department of Otolaryngology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. 2. Department of Neurosurgery, The Johns Hopkins University School of Medicine, 1550 Orleans St, Rm 2M-51, Baltimore, MD, 21287, USA. 3. Department of Neurological Surgery, Mayo Clinic School of Medicine, Rochester, MN, USA. 4. Department of Neurosurgery, The Johns Hopkins University School of Medicine, 1550 Orleans St, Rm 2M-51, Baltimore, MD, 21287, USA. christinaa.holmes@gmail.com.
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.
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.
Authors: Yu-An Cao; Amy J Wagers; Andreas Beilhack; Joan Dusich; Michael H Bachmann; Robert S Negrin; Irving L Weissman; Christopher H Contag Journal: Proc Natl Acad Sci U S A Date: 2003-12-19 Impact factor: 11.205
Authors: Yu-An Cao; Michael H Bachmann; Andreas Beilhack; Yang Yang; Masashi Tanaka; Rutger-Jan Swijnenburg; Robert Reeves; Cariel Taylor-Edwards; Stephan Schulz; Timothy C Doyle; C Garrison Fathman; Robert C Robbins; Leonore A Herzenberg; Robert S Negrin; Christopher H Contag Journal: Transplantation Date: 2005-07-15 Impact factor: 4.939
Authors: Daniel Neen; David Noyes; Matthew Shaw; Stephen Gwilym; Neil Fairlie; Nicholas Birch Journal: Spine (Phila Pa 1976) Date: 2006-08-15 Impact factor: 3.468
Authors: Ruth E Geuze; Henk-Jan Prins; F Cumhur Öner; Yvonne J M van der Helm; Leontine S Schuijff; Anton C Martens; Moyo C Kruyt; Jacqueline Alblas; Wouter J A Dhert Journal: Tissue Eng Part A Date: 2010-07-13 Impact factor: 3.845
Authors: Ahmad Y Sheikh; Shu-An Lin; Feng Cao; Yuan Cao; Koen E A van der Bogt; Pauline Chu; Ching-Pin Chang; Christopher H Contag; Robert C Robbins; Joseph C Wu Journal: Stem Cells Date: 2007-07-12 Impact factor: 6.277
Authors: Andrew L Alejo; Scott McDermott; Yusuf Khalil; Hope C Ball; Gabrielle T Robinson; Ernesto Solorzano; Amanda M Alejo; Jacob Douglas; Trinity K Samson; Jesse W Young; Fayez F Safadi Journal: J Orthop Sports Med Date: 2022-09-05
Authors: Christina Holmes; Benjamin D Elder; Wataru Ishida; Alexander Perdomo-Pantoja; John Locke; Ethan Cottrill; Sheng-Fu L Lo; Timothy F Witham Journal: J Orthop Surg Res Date: 2020-09-15 Impact factor: 2.359