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

Chris D. Daly, Peter Ghosh, Andrew C.W. Zannettino, Tanya Badal, Ronald Shimmon, Graham Jenkin, David Oehme, Kanika Jain, Idrees Sher, Angela Vais, Camilla Cohen, Ronil V. Chandra, Tony Goldschlager

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)491-506
Number of pages16
JournalSpine Journal
Volume18
Issue number3
DOIs
Publication statusPublished - 1 Mar 2018

Keywords

  • Adult stem cells
  • Disc degeneration
  • Intervertebral disc
  • Mesenchymal precursor cells
  • Microdiscectomy
  • Pentosan polysulfate

Cite this

Daly, Chris D. ; Ghosh, Peter ; Zannettino, Andrew C.W. ; Badal, Tanya ; Shimmon, Ronald ; Jenkin, Graham ; Oehme, David ; Jain, Kanika ; Sher, Idrees ; Vais, Angela ; Cohen, Camilla ; Chandra, Ronil V. ; Goldschlager, Tony. / Mesenchymal progenitor cells primed with pentosan polysulfate promote lumbar intervertebral disc regeneration in an ovine model of microdiscectomy. In: Spine Journal. 2018 ; Vol. 18, No. 3. pp. 491-506.
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title = "Mesenchymal progenitor cells primed with pentosan polysulfate promote lumbar intervertebral disc regeneration in an ovine model of microdiscectomy",
abstract = "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.",
keywords = "Adult stem cells, Disc degeneration, Intervertebral disc, Mesenchymal precursor cells, Microdiscectomy, Pentosan polysulfate",
author = "Daly, {Chris D.} and Peter Ghosh and Zannettino, {Andrew C.W.} and Tanya Badal and Ronald Shimmon and Graham Jenkin and David Oehme and Kanika Jain and Idrees Sher and Angela Vais and Camilla Cohen and Chandra, {Ronil V.} and Tony Goldschlager",
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language = "English",
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Mesenchymal progenitor cells primed with pentosan polysulfate promote lumbar intervertebral disc regeneration in an ovine model of microdiscectomy. / Daly, Chris D.; Ghosh, Peter; Zannettino, Andrew C.W.; Badal, Tanya; Shimmon, Ronald; Jenkin, Graham; Oehme, David; Jain, Kanika; Sher, Idrees; Vais, Angela; Cohen, Camilla; Chandra, Ronil V.; Goldschlager, Tony.

In: Spine Journal, Vol. 18, No. 3, 01.03.2018, p. 491-506.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Mesenchymal progenitor cells primed with pentosan polysulfate promote lumbar intervertebral disc regeneration in an ovine model of microdiscectomy

AU - Daly, Chris D.

AU - Ghosh, Peter

AU - Zannettino, Andrew C.W.

AU - Badal, Tanya

AU - Shimmon, Ronald

AU - Jenkin, Graham

AU - Oehme, David

AU - Jain, Kanika

AU - Sher, Idrees

AU - Vais, Angela

AU - Cohen, Camilla

AU - Chandra, Ronil V.

AU - Goldschlager, Tony

PY - 2018/3/1

Y1 - 2018/3/1

N2 - 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.

AB - 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.

KW - Adult stem cells

KW - Disc degeneration

KW - Intervertebral disc

KW - Mesenchymal precursor cells

KW - Microdiscectomy

KW - Pentosan polysulfate

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U2 - 10.1016/j.spinee.2017.10.008

DO - 10.1016/j.spinee.2017.10.008

M3 - Article

VL - 18

SP - 491

EP - 506

JO - Spine Journal

JF - Spine Journal

SN - 1529-9430

IS - 3

ER -