Treatment of Naturally Degenerated Canine Lumbosacral Intervertebral Discs with Autologous Mesenchymal Stromal Cells and Collagen Microcarriers: A Prospective Clinical Study
Intervertebral disc (IVD) degeneration is a frequent disease in modern societies and at its later stages is likely to cause chronic low back pain. Although many studies have been published, the available treatments for IVD degeneration fail to promote regeneration or even marginal repair of the IVD...
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doaj-82486e6336d7483f96415fe771049a022020-11-25T03:52:03ZengSAGE PublishingCell Transplantation0963-68971555-38922019-02-012810.1177/0963689718815459Treatment of Naturally Degenerated Canine Lumbosacral Intervertebral Discs with Autologous Mesenchymal Stromal Cells and Collagen Microcarriers: A Prospective Clinical StudyFrank Steffen0Alessandro Bertolo1Remo Affentranger2Stephen J. Ferguson3Jivko Stoyanov4 Vetsuisse faculty of the University of Zurich, Zurich, Switzerland Swiss Paraplegic Research, Nottwil, Switzerland. Institute for Biomechanics, ETH, Zurich, Switzerland Institute for Biomechanics, ETH, Zurich, Switzerland Institute for Surgical Technology and Biomechanics, University of Bern, Bern, SwitzerlandIntervertebral disc (IVD) degeneration is a frequent disease in modern societies and at its later stages is likely to cause chronic low back pain. Although many studies have been published, the available treatments for IVD degeneration fail to promote regeneration or even marginal repair of the IVD structure. In this study, we aimed to establish veterinary canine patients as a translational large animal model that recapitulates IVD degeneration that occurs in humans, and to investigate the suitability of intradiscal application of mesenchymal stromal cells (MSC). Twenty client-owned dogs diagnosed with spontaneous degenerative lumbosacral IVD and low back pain were included in the study. Autologous MSC were isolated from bone marrow and cultured for 2 weeks. Prior to injection, MSC were attached on collagen microcarriers for delivery, with or without TGF-β1 crosslinking. After decompressive spinal surgery, dogs received an intradiscal injection of MSC-microcarriers ( n = 11), MSC-TGF-β1-microcarriers ( n = 6) or microcarriers only (control, n = 3). MSC-microcarriers were initially evaluated in vitro and ex vivo , to test cell chondrogenic potential and biomechanical properties of the microcarriers, respectively. Clinical performance and Pfirrmann grading were evaluated at 10 months after the injection by magnetic resonance imaging. MSC differentiated successfully in vitro towards chondrogenic phenotype and biomechanical tests showed no significant differences of IVD stiffness after microcarrier injection. In vivo injection was successful in all dogs, without any visible leakage, and clinical functioning was restored back to normality. However, postoperative Pfirrmann grade remained identical in all dogs, and formation of Schmorl’s nodes was detected in 45% of dogs. This side effect was reduced by halving the injection volume, which was then observed only in 11% of dogs. In conclusion, we observed marked clinical improvement in all groups, despite the formation of Schmorl’s nodes, but microcarriers and MSC failed to regenerate the structure of degenerated IVD.https://doi.org/10.1177/0963689718815459 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Frank Steffen Alessandro Bertolo Remo Affentranger Stephen J. Ferguson Jivko Stoyanov |
spellingShingle |
Frank Steffen Alessandro Bertolo Remo Affentranger Stephen J. Ferguson Jivko Stoyanov Treatment of Naturally Degenerated Canine Lumbosacral Intervertebral Discs with Autologous Mesenchymal Stromal Cells and Collagen Microcarriers: A Prospective Clinical Study Cell Transplantation |
author_facet |
Frank Steffen Alessandro Bertolo Remo Affentranger Stephen J. Ferguson Jivko Stoyanov |
author_sort |
Frank Steffen |
title |
Treatment of Naturally Degenerated Canine Lumbosacral Intervertebral Discs with Autologous Mesenchymal Stromal Cells and Collagen Microcarriers: A Prospective Clinical Study |
title_short |
Treatment of Naturally Degenerated Canine Lumbosacral Intervertebral Discs with Autologous Mesenchymal Stromal Cells and Collagen Microcarriers: A Prospective Clinical Study |
title_full |
Treatment of Naturally Degenerated Canine Lumbosacral Intervertebral Discs with Autologous Mesenchymal Stromal Cells and Collagen Microcarriers: A Prospective Clinical Study |
title_fullStr |
Treatment of Naturally Degenerated Canine Lumbosacral Intervertebral Discs with Autologous Mesenchymal Stromal Cells and Collagen Microcarriers: A Prospective Clinical Study |
title_full_unstemmed |
Treatment of Naturally Degenerated Canine Lumbosacral Intervertebral Discs with Autologous Mesenchymal Stromal Cells and Collagen Microcarriers: A Prospective Clinical Study |
title_sort |
treatment of naturally degenerated canine lumbosacral intervertebral discs with autologous mesenchymal stromal cells and collagen microcarriers: a prospective clinical study |
publisher |
SAGE Publishing |
series |
Cell Transplantation |
issn |
0963-6897 1555-3892 |
publishDate |
2019-02-01 |
description |
Intervertebral disc (IVD) degeneration is a frequent disease in modern societies and at its later stages is likely to cause chronic low back pain. Although many studies have been published, the available treatments for IVD degeneration fail to promote regeneration or even marginal repair of the IVD structure. In this study, we aimed to establish veterinary canine patients as a translational large animal model that recapitulates IVD degeneration that occurs in humans, and to investigate the suitability of intradiscal application of mesenchymal stromal cells (MSC). Twenty client-owned dogs diagnosed with spontaneous degenerative lumbosacral IVD and low back pain were included in the study. Autologous MSC were isolated from bone marrow and cultured for 2 weeks. Prior to injection, MSC were attached on collagen microcarriers for delivery, with or without TGF-β1 crosslinking. After decompressive spinal surgery, dogs received an intradiscal injection of MSC-microcarriers ( n = 11), MSC-TGF-β1-microcarriers ( n = 6) or microcarriers only (control, n = 3). MSC-microcarriers were initially evaluated in vitro and ex vivo , to test cell chondrogenic potential and biomechanical properties of the microcarriers, respectively. Clinical performance and Pfirrmann grading were evaluated at 10 months after the injection by magnetic resonance imaging. MSC differentiated successfully in vitro towards chondrogenic phenotype and biomechanical tests showed no significant differences of IVD stiffness after microcarrier injection. In vivo injection was successful in all dogs, without any visible leakage, and clinical functioning was restored back to normality. However, postoperative Pfirrmann grade remained identical in all dogs, and formation of Schmorl’s nodes was detected in 45% of dogs. This side effect was reduced by halving the injection volume, which was then observed only in 11% of dogs. In conclusion, we observed marked clinical improvement in all groups, despite the formation of Schmorl’s nodes, but microcarriers and MSC failed to regenerate the structure of degenerated IVD. |
url |
https://doi.org/10.1177/0963689718815459 |
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