Delayed Endothelial Progenitor Cell Therapy Promotes Bone Defect Repair in a Clinically Relevant Rat Model

The repair of segmental bone defects remains a significant challenge for orthopaedic surgeons. Endothelial progenitor cells (EPCs) have successfully promoted the repair of acute defects in animal models; however, the ability of EPCs to induce the repair of chronic nonhealing defects, such as those o...

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Main Authors: Brent D. Bates, Charles Godbout, David J. Ramnaraign, Emil H. Schemitsch, Aaron Nauth
Format: Article
Language:English
Published: Hindawi Limited 2017-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2017/7923826
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spelling doaj-83e7c765f4a5426fb25d05a030e0354a2020-11-25T00:31:12ZengHindawi LimitedStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/79238267923826Delayed Endothelial Progenitor Cell Therapy Promotes Bone Defect Repair in a Clinically Relevant Rat ModelBrent D. Bates0Charles Godbout1David J. Ramnaraign2Emil H. Schemitsch3Aaron Nauth4Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, University of Toronto, 209 Victoria Street, Toronto, ON, M5B 1T8, CanadaKeenan Research Centre for Biomedical Science, St. Michael’s Hospital, University of Toronto, 209 Victoria Street, Toronto, ON, M5B 1T8, CanadaKeenan Research Centre for Biomedical Science, St. Michael’s Hospital, University of Toronto, 209 Victoria Street, Toronto, ON, M5B 1T8, CanadaDepartment of Surgery, London Health Sciences Centre, 339 Windermere Road, London, ON, N6A 5A5, CanadaKeenan Research Centre for Biomedical Science, St. Michael’s Hospital, University of Toronto, 209 Victoria Street, Toronto, ON, M5B 1T8, CanadaThe repair of segmental bone defects remains a significant challenge for orthopaedic surgeons. Endothelial progenitor cells (EPCs) have successfully promoted the repair of acute defects in animal models; however, the ability of EPCs to induce the repair of chronic nonhealing defects, such as those often encountered clinically, has not been investigated. Therefore, the purpose of this study was to investigate the ability of EPCs delivered in delayed fashion to induce the repair of nonhealing defects in a clinically relevant model. In order to simulate delayed treatment, 5 mm segmental defects in Fischer 344 rat femora were treated with bone marrow-derived EPCs on a Gelfoam scaffold at 3 weeks post creation of the defect. At ten weeks posttreatment, 100% of EPC-treated defects achieved union, whereas complete union was only achieved in 37.5% of defects treated with Gelfoam alone. Furthermore, significant increases in ultimate torque (p=0.022) and torsional stiffness (p=0.003) were found in EPC-treated defects compared to controls. Critically, no differences in outcomes were observed between acute and delayed EPC treatments. These results suggest that EPCs can enhance bone healing when applied in an acute or delayed fashion and that their use may represent a clinically translatable therapy for bone healing in humans.http://dx.doi.org/10.1155/2017/7923826
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language English
format Article
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author Brent D. Bates
Charles Godbout
David J. Ramnaraign
Emil H. Schemitsch
Aaron Nauth
spellingShingle Brent D. Bates
Charles Godbout
David J. Ramnaraign
Emil H. Schemitsch
Aaron Nauth
Delayed Endothelial Progenitor Cell Therapy Promotes Bone Defect Repair in a Clinically Relevant Rat Model
Stem Cells International
author_facet Brent D. Bates
Charles Godbout
David J. Ramnaraign
Emil H. Schemitsch
Aaron Nauth
author_sort Brent D. Bates
title Delayed Endothelial Progenitor Cell Therapy Promotes Bone Defect Repair in a Clinically Relevant Rat Model
title_short Delayed Endothelial Progenitor Cell Therapy Promotes Bone Defect Repair in a Clinically Relevant Rat Model
title_full Delayed Endothelial Progenitor Cell Therapy Promotes Bone Defect Repair in a Clinically Relevant Rat Model
title_fullStr Delayed Endothelial Progenitor Cell Therapy Promotes Bone Defect Repair in a Clinically Relevant Rat Model
title_full_unstemmed Delayed Endothelial Progenitor Cell Therapy Promotes Bone Defect Repair in a Clinically Relevant Rat Model
title_sort delayed endothelial progenitor cell therapy promotes bone defect repair in a clinically relevant rat model
publisher Hindawi Limited
series Stem Cells International
issn 1687-966X
1687-9678
publishDate 2017-01-01
description The repair of segmental bone defects remains a significant challenge for orthopaedic surgeons. Endothelial progenitor cells (EPCs) have successfully promoted the repair of acute defects in animal models; however, the ability of EPCs to induce the repair of chronic nonhealing defects, such as those often encountered clinically, has not been investigated. Therefore, the purpose of this study was to investigate the ability of EPCs delivered in delayed fashion to induce the repair of nonhealing defects in a clinically relevant model. In order to simulate delayed treatment, 5 mm segmental defects in Fischer 344 rat femora were treated with bone marrow-derived EPCs on a Gelfoam scaffold at 3 weeks post creation of the defect. At ten weeks posttreatment, 100% of EPC-treated defects achieved union, whereas complete union was only achieved in 37.5% of defects treated with Gelfoam alone. Furthermore, significant increases in ultimate torque (p=0.022) and torsional stiffness (p=0.003) were found in EPC-treated defects compared to controls. Critically, no differences in outcomes were observed between acute and delayed EPC treatments. These results suggest that EPCs can enhance bone healing when applied in an acute or delayed fashion and that their use may represent a clinically translatable therapy for bone healing in humans.
url http://dx.doi.org/10.1155/2017/7923826
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