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Title: | Mesenchymal progenitor cells primed with pentosan polysulfate promote lumbar intervertebral disc regeneration in an ovine model of microdiscectomy. | Authors: | Oehme D.;Jain K.;Sher I.;Vais A.;Cohen C.;Chandra R.V.;Goldschlager T. ;Daly C.D.;Ghosh P.;Zannettino A.C.W.;Badal T.;Shimmon R.;Jenkin G. | Institution: | (Daly, Sher, Chandra, Goldschlager) Department of Surgery, Monash University, 246 Clayton Rd, Clayton, VIC 3168, Australia (Daly, Sher, Goldschlager) Department of Neurosurgery, Monash Medical Centre, 246 Clayton Rd, Clayton, VIC 3168, Australia (Daly, Ghosh, Jenkin, Jain, Goldschlager) The Ritchie Centre, Hudson Institute of Medical Research, Monash University, 246 Clayton Rd, Clayton, VIC 3168, Australia (Ghosh) Proteobioactives Pty Ltd, PO Box 174, Balgowlah, NSW 2093, Australia (Zannettino) Myeloma Research Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA 5000, Australia (Zannettino) Cancer Theme, South Australia Health and Medical Research Institute (SAHMRI), North Terrace, Adelaide, SA 5000, Australia (Badal, Shimmon) Chemical Technology Unit, Faculty of Science, University of Technology, 15 Broadway, Ultimo, Sydney, NSW 2007, Australia (Jenkin) Department of Obstetrics and Gynaecology, Monash University, 246 Clayton Rd, Clayton, VIC 3168, Australia (Oehme) Department of Neurosurgery, St Vincent's Hospital, 41 Victoria Pde, Fitzroy, VIC 3065, Australia (Vais, Cohen) Monash Histology Platform, Monash University, Wellington Rd, Clayton, VIC 3168, Australia (Chandra) Monash Department of Radiology, Monash Medical Centre, 246 Clayton Rd, Clayton, VIC 3168, Australia | Issue Date: | 21-Mar-2018 | Copyright year: | 2018 | Publisher: | Elsevier Inc. (E-mail: usjcs@elsevier.com) | Place of publication: | United States | Publication information: | Spine Journal. 18 (3) (pp 491-506), 2018. Date of Publication: March 2018. | Journal: | Spine Journal | 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(s): 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. Method(s): 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 (5x105 cells) or pMPC (5x105 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. Result(s): 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. Conclusion(s): 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.Copyright © 2017 Elsevier Inc. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1016/j.spinee.2017.10.008 | ORCID: | Daly, Chris D.; ORCID: http://orcid.org/0000-0003-1407-9330 Shimmon, Ronald; ORCID: http://orcid.org/0000-0002-8763-991X | Link to associated publication: | Click here for full text options | PubMed URL: | 29055739 [http://www.ncbi.nlm.nih.gov/pubmed/?term=29055739] | ISSN: | 1529-9430 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/37360 | Type: | Article | Subjects: | radiography collagen/ec [Endogenous Compound] collagen sponge DNA/ec [Endogenous Compound] glycosaminoglycan polysulfate/ec [Endogenous Compound] *pentosan polysulfate/dt [Drug Therapy] proteoglycan/ec [Endogenous Compound] nuclear magnetic resonance scanner microdiscectomy Siemens Skyra Widebore 3T MRI adult animal experiment animal model annulus fibrosus article biochemical analysis collagen fiber controlled study discectomy DNA content ewe female histology *intervertebral disk degeneration/dt [Drug Therapy] *mesenchymal stem cell microscopy microsurgery nonhuman nuclear magnetic resonance imaging ovine model priority journal microscopy microsurgery nonhuman nuclear magnetic resonance imaging ovine model priority journal radiography biochemical analysis animal experiment collagen fiber controlled study discectomy DNA content ewe female histology *intervertebral disk degeneration / *drug therapy *mesenchymal stem cell Article annulus fibrosus animal model adult |
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