Mesenchymal progenitor cells combined with pentosan polysulfate mediating disc regeneration at the time of microdiscectomy: a preliminary study in an ovine model

Oehme, David; Ghosh, Peter; Shimmon, Susan; Wu, Jiehua; McDonald, Courtney; Troupis, John; Goldschlager, Tony; Rosenfeld, Jeffrey V.; Jenkin, Graham

doi:10.3171/2014.2.spine13760

Cited by 64 publications

(80 citation statements)

References 90 publications

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“…Formulations that contain low-dose MPCs in combination with PPS have been shown to enhance disc regeneration in other animal models, 20,50 but the mechanism(s) of action remains speculative. In vitro studies have found that a combination of MPCs and PPS increases MPC viability and reduces apoptosis and TACE (ADAM-17) production while supporting proliferation and chondrogenic differentiation.…”

Section: 6165mentioning

confidence: 99%

Reconstitution of degenerated ovine lumbar discs by STRO-3–positive allogeneic mesenchymal precursor cells combined with pentosan polysulfate

Oehme

Ghosh

Goldschlager

et al. 2016

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OBJECTIVE Disc degeneration and associated low-back pain are major causes of suffering and disability. The authors examined the potential of mesenchymal precursor cells (MPCs), when formulated with pentosan polysulfate (PPS), to ameliorate disc degeneration in an ovine model. METHODS Twenty-four sheep had annular incisions made at L2–3, L3–4, and L4–5 to induce degeneration. Twelve weeks after injury, the nucleus pulposus of a degenerated disc in each animal was injected with ProFreeze and PPS formulated with either a low dose (0.1 million MPCs) or a high dose (0.5 million MPCs) of cells. The 2 adjacent injured discs in each spine were either injected with PPS and ProFreeze (PPS control) or not injected (nil-injected control). The adjacent noninjured L1–2 and L5–6 discs served as noninjured control discs. Disc height indices (DHIs) were obtained at baseline, before injection, and at planned death. After necropsy, 24 weeks after injection, the spines were subjected to MRI and morphological, histological, and biochemical analyses. RESULTS Twelve weeks after the annular injury, all the injured discs exhibited a significant reduction in mean DHI (low-dose group 17.19%; high-dose group 18.01% [p < 0.01]). Twenty-four weeks after injections, the discs injected with the low-dose MPC+PPS formulation recovered disc height, and their mean DHI was significantly greater than the DHI of PPS- and nil-injected discs (p < 0.001). Although the mean Pfirrmann MRI disc degeneration score for the low-dose MPC+PPS–injected discs was lower than that for the nil- and PPS-injected discs, the differences were not significant. The disc morphology scores for the nil- and PPS-injected discs were significantly higher than the normal control disc scores (p < 0.005), whereas the low-dose MPC+PPS–injected disc scores were not significantly different from those of the normal controls. The mean glycosaminoglycan content of the nuclei pulposus of the low-dose MPC+PPS–injected discs was significantly higher than that of the PPS-injected controls (p < 0.05) but was not significantly different from the normal control disc glycosaminoglycan levels. Histopathology degeneration frequency scores for the low-dose MPC+PPS–injected discs were lower than those for the PPS- and Nil-injected discs. The corresponding high-dose MPC+PPS–injected discs failed to show significant improvements in any outcome measure relative to the controls. CONCLUSIONS Intradiscal injections of a formulation composed of 0.1 million MPCs combined with PPS resulted in positive effects in reducing the progression of disc degeneration in an ovine model, as assessed by improvements in DHI and morphological, biochemical, and histopathological scores.

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Section: 6165mentioning

confidence: 99%

Reconstitution of degenerated ovine lumbar discs by STRO-3–positive allogeneic mesenchymal precursor cells combined with pentosan polysulfate

Oehme

Ghosh

Goldschlager

et al. 2016

SPI

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“…4). The results obtained from this study demonstrated restoration of the proteoglycan content of the nucleus pulposus, preservation of disc height and MRI T2 signal and improved histological morphology in discs treated with MPCs and PPS [32, 33, 94,95]. These preliminary results are promising, although further more rigorous preclinical studies are required and are currently underway prior to the translation of this technique into clinical practice.…”

Section: Microdiscectomymentioning

confidence: 49%

The role of stem cell therapies in degenerative lumbar spine disease: a review

et al. 2015

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Degenerative conditions of the lumbar spine are extremely common. Ninety percent of people over the age of 60 years have degenerative change on imaging; however, only a small minority of people will require spine surgery (Hicks et al. Spine (Phila Pa 1976) 34(12):1301-1306, 2009). This minority, however, constitutes a core element of spinal surgery practice. Whilst the patient outcomes from spinal surgeries have improved in recent years, some patients will remain with pain and disability despite technically successful surgery. Advances in regenerative medicine and stem cell therapies, particularly the use of mesenchymal stem cells and allogeneic mesenchymal precursor cells, have led to numerous clinical trials utilising these cell-based therapies to treat degenerative spinal conditions. Through cartilage formation and disc regeneration, fusion enhancement or via modification of pain pathways, stem cells are well suited to enhance spinal surgery practice. This review will focus on the outcomes of lumbar spinal procedures and the role of stem cells in the treatment of degenerative lumbar conditions to enhance clinical practice. The current status of clinical trials utilising stem cell therapies will be discussed, providing clinicians with an overview of the various cell-based treatments likely to be available to patients in the near future.

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“…Therefore, these studies suggest that both trafficking and retention of cells are increased in the presence of disease. We have also shown that, when MPCs are injected into both injured and non-injured spinal disks, the infiltration of immune cells is not different, suggesting that in the presence of injury MPCs did not alternatively activate the immune system in this situation [35]. Moreover, we know that cells can respond to their surrounding environment and alter their cell surface markers and the secretion of trophic factors.…”

Section: Discussionmentioning

confidence: 92%

Evaluation of the safety and tolerability of a high-dose intravenous infusion of allogeneic mesenchymal precursor cells

et al. 2015

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Mesenchymal progenitor cells combined with pentosan polysulfate mediating disc regeneration at the time of microdiscectomy: a preliminary study in an ovine model

Cited by 64 publications

References 90 publications

Reconstitution of degenerated ovine lumbar discs by STRO-3–positive allogeneic mesenchymal precursor cells combined with pentosan polysulfate

Reconstitution of degenerated ovine lumbar discs by STRO-3–positive allogeneic mesenchymal precursor cells combined with pentosan polysulfate

The role of stem cell therapies in degenerative lumbar spine disease: a review

Evaluation of the safety and tolerability of a high-dose intravenous infusion of allogeneic mesenchymal precursor cells

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