Mesenchymal progenitor cells primed with pentosan polysulfate promote lumbar intervertebral disc regeneration in an ovine model of microdiscectomy

Daly, CD; Ghosh, P; Zannettino, ACW; Badal, T; Shimmon, R; Jenkin, G; Oehme, D; Jain, K; Sher, I; Vais, A; Cohen, C; Chandra, RV; Goldschlager, T

Mesenchymal progenitor cells primed with pentosan polysulfate promote lumbar intervertebral disc regeneration in an ovine model of microdiscectomy

Daly, CD Ghosh, P Zannettino, ACW Badal, T Shimmon, R

Jenkin, G Oehme, D Jain, K Sher, I Vais, A Cohen, C Chandra, RV Goldschlager, T

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Publication Type:: Journal Article
Citation:: Spine Journal, 2018, 18 (3), pp. 491 - 506
Issue Date:: 2018-03-01

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Field	Value	Language
dc.contributor.author	Daly, CD	en_US
dc.contributor.author	Ghosh, P	en_US
dc.contributor.author	Zannettino, ACW	en_US
dc.contributor.author	Badal, T	en_US
dc.contributor.author	Shimmon, R https://orcid.org/0000-0002-8763-991X	en_US
dc.contributor.author	Jenkin, G	en_US
dc.contributor.author	Oehme, D	en_US
dc.contributor.author	Jain, K	en_US
dc.contributor.author	Sher, I	en_US
dc.contributor.author	Vais, A	en_US
dc.contributor.author	Cohen, C	en_US
dc.contributor.author	Chandra, RV	en_US
dc.contributor.author	Goldschlager, T	en_US
dc.date.available	2017-10-05	en_US
dc.date.issued	2018-03-01	en_US
dc.identifier.citation	Spine Journal, 2018, 18 (3), pp. 491 - 506	en_US
dc.identifier.issn	1529-9430	en_US
dc.identifier.uri	http://hdl.handle.net/10453/125123
dc.description.abstract	© 2017 Elsevier Inc. Background Context: Neural compression associated with lumbar disc herniation is usually managed surgically by microdiscectomy. However, 10%–20% of patients re-present with debilitating back pain, and approximately 15% require further surgery. Purpose: Using an ovine model of microdiscectomy, the present study investigated the relative potential of pentosan polysulfate-primed mesenchymal progenitor cells (pMPCs) or MPC alone implanted into the lesion site to facilitate disc recovery. Study Design: An ovine model of lumbar microdiscectomy was used to compare the relative outcomes of administering MPCs or pMPCs to the injury site postsurgery. Methods: At baseline 3T magnetic resonance imaging (MRI) of 18 adult ewes was undertaken followed by annular microdiscectomy at two lumbar disc levels. Sheep were randomized into three groups (n=6). The injured controls received no further treatment. Defects of the treated groups were implanted with a collagen sponge and MPC (5×105 cells) or pMPC (5×105 cells). After 6 months, 3T MRI and standard radiography were performed. Spinal columns were dissected, individual lumbar discs were sectioned horizontally, and nucleus pulposus (NP) and annulus fibrosus (AF) regions were assessed morphologically and histologically. The NP and AF tissues were dissected into six regions and analyzed biochemically for their proteoglycans (PGs), collagen, and DNA content. Results: Both the MPC- and pMPC-injected groups exhibited less reduction in disc height (p<.05) and lower Pfirrmann grades (p≤.001) compared with the untreated injury controls, but morphologic scores for the pMPC-injected discs were lower (p<.05). The PG content of the AF injury site region (AF1) of pMPC discs was higher than MPC and injury control AF1 (p<.05). At the AF1 and contralateral AF2 regions, the DNA content of pMPC discs was significantly lower than injured control discs and MPC-injected discs. Histologic and birefringent microscopy revealed increased structural organization and reduced degeneration in pMPC discs compared with MPC and the injured controls. Conclusions: In an ovine model 6 months after administration of pMPCs to the injury site disc PG content and matrix organization were improved relative to controls, suggesting pMPCs’ potential as a postsurgical adjunct for limiting progression of disc degeneration after microdiscectomy.	en_US
dc.relation.ispartof	Spine Journal	en_US
dc.relation.isbasedon	10.1016/j.spinee.2017.10.008	en_US
dc.subject.classification	Orthopedics	en_US
dc.subject.mesh	Lumbosacral Region	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Diskectomy	en_US
dc.subject.mesh	Intervertebral Disc	en_US
dc.subject.mesh	Intervertebral Disc Degeneration	en_US
dc.subject.mesh	Mesenchymal Stem Cell Transplantation	en_US
dc.subject.mesh	Mesenchymal Stem Cells	en_US
dc.subject.mesh	Pentosan Sulfuric Polyester	en_US
dc.subject.mesh	Regeneration	en_US
dc.subject.mesh	Sheep	en_US
dc.title	Mesenchymal progenitor cells primed with pentosan polysulfate promote lumbar intervertebral disc regeneration in an ovine model of microdiscectomy	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	18	en_US
utslib.for	1103 Clinical Sciences	en_US
utslib.for	1109 Neurosciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CCET - Centre for Clean Energy Technology
utslib.copyright.status	closed_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	18	en_US

Abstract:

© 2017 Elsevier Inc. Background Context: Neural compression associated with lumbar disc herniation is usually managed surgically by microdiscectomy. However, 10%–20% of patients re-present with debilitating back pain, and approximately 15% require further surgery. Purpose: Using an ovine model of microdiscectomy, the present study investigated the relative potential of pentosan polysulfate-primed mesenchymal progenitor cells (pMPCs) or MPC alone implanted into the lesion site to facilitate disc recovery. Study Design: An ovine model of lumbar microdiscectomy was used to compare the relative outcomes of administering MPCs or pMPCs to the injury site postsurgery. Methods: At baseline 3T magnetic resonance imaging (MRI) of 18 adult ewes was undertaken followed by annular microdiscectomy at two lumbar disc levels. Sheep were randomized into three groups (n=6). The injured controls received no further treatment. Defects of the treated groups were implanted with a collagen sponge and MPC (5×105 cells) or pMPC (5×105 cells). After 6 months, 3T MRI and standard radiography were performed. Spinal columns were dissected, individual lumbar discs were sectioned horizontally, and nucleus pulposus (NP) and annulus fibrosus (AF) regions were assessed morphologically and histologically. The NP and AF tissues were dissected into six regions and analyzed biochemically for their proteoglycans (PGs), collagen, and DNA content. Results: Both the MPC- and pMPC-injected groups exhibited less reduction in disc height (p<.05) and lower Pfirrmann grades (p≤.001) compared with the untreated injury controls, but morphologic scores for the pMPC-injected discs were lower (p<.05). The PG content of the AF injury site region (AF1) of pMPC discs was higher than MPC and injury control AF1 (p<.05). At the AF1 and contralateral AF2 regions, the DNA content of pMPC discs was significantly lower than injured control discs and MPC-injected discs. Histologic and birefringent microscopy revealed increased structural organization and reduced degeneration in pMPC discs compared with MPC and the injured controls. Conclusions: In an ovine model 6 months after administration of pMPCs to the injury site disc PG content and matrix organization were improved relative to controls, suggesting pMPCs’ potential as a postsurgical adjunct for limiting progression of disc degeneration after microdiscectomy.

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http://hdl.handle.net/10453/125123