Investigation of the Effect of Secreted Factors from Mesenchymal Stem Cells on Disc Cells from Degenerated Discs

Low back pain is experienced by a large number of people in western countries and may be caused and influenced by many different pathologies and psychosocial factors including disc degeneration. Disc degeneration involves the increased expression of proinflammatory cytokines and matrix metalloproteinases (MMPs) in the disc environment, which leads to the loss of extracellular matrix (ECM) and the viability of the native disc cells (DCs). Treatment approaches using growth factors and cell therapy have been proposed due to the compelling results that growth factors and mesenchymal stem cells (MSCs) can influence the degenerated discs. The aim of this study was to investigate the effects of conditioned media (CM) from human MSCs (hMSCs) and connective tissue growth factor (CTGF) and TGF-β on disc cells, and hMSCs isolated from patients with degenerative discs and severe low back pain. The aim was also to examine the constituents of CM in order to study the peptides that could bring about intervertebral disc (IVD) regeneration. DCs and hMSC pellets (approx.. 200,000 cells) were cultured and stimulated with hMSC-derived CM or CTGF and TGF-β over 28 days. The effects of CM and CTGF on DCs and hMSCs were assessed via cell viability, proteoglycan production, the expression of ECM proteins, and chondrogenesis in 3D pellet culture. To identify the constituents of CM, CM was analyzed with tandem mass spectrometry. The findings indicate that CM enhanced the cellular viability and ECM production of DCs while CTGF and the control exhibited nonsignificant differences. The same was observed in the hMSC group. Mass spectrometry analysis of CM identified >700 peptides, 129 of which showed a relative abundance of ≥2 (CTGF among them). The results suggest that CM holds potential to counter the progression of disc degeneration, likely resulting from the combination of all the substances released by the hMSCs. The soluble factors released belong to different peptide families. The precise mechanism underlying the regenerative effect needs to be investigated further, prior to incorporating peptides in the development of new treatment strategies for low back pain that is potentially caused by IVD degeneration

The impact of implementing a person-centred pain management intervention on resistance to change and organizational culture

Background: Resistance to change and organizational culture are essential factors to consider in change management in health care settings. Implementation of structural change remains a challenge. There is a lack of studies providing information on the impact of implementation processes on the organization. The aim of this study was to describe the impact of implementing a systematic change process concerning postoperative person-centred pain management on resistance to change and organizational culture in an orthopaedic spine surgery unit. Methods: The study was set in an orthopaedic spine surgery unit at a university hospital. Person-centred bundles of care for postoperative pain management of spine surgery patients were developed in co-creation by a multi-professional expert group and implemented throughout the care pathway. The intervention was underpinned by theories on organizational culture and inspired by principles of person-centred care. Quantitative data were collected using the Resistance to Change Scale and the Organizational Culture Assessment Instrument and analysed using descriptive statistics. Results: The findings showed a low resistance to change decreasing during the study. The organizational culture shifted from a result-oriented to a formalized and structured culture after the implementation. The culture preferred by the staff was team-oriented and participation-focused throughout the study. The discrepancy between the current and preferred cultures remained extensive over time. Conclusion: It is challenging to describe the influence of the development and implementation of a postoperative pain management program on organizational culture as well as in terms of resistance to change, in a complex health care setting. In the current study the unit was under organizational strain during the implementation. Albeit, the important discrepancy between the current and preferred organizational culture could imply that structural changes aren’t enough when implementing person-centred pain management structures and needs to be combined with relational aspects of change

Percutaneous Interspinous Spacer vs Decompression in Patients with Neurogenic Claudication: An Alternative in Selected Patients?

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesBACKGROUND: Standalone interspinous process devices (IPDs) to treat degenerative lumbar spinal stenosis with neurogenic intermittent claudication (NIC) have shown ambiguous results in the literature. OBJECTIVE: To show that a minimally invasive percutaneous IPD is safe and noninferior to standalone decompressive surgery (SDS) for patients with degenerative lumbar spinal stenosis with NIC. METHODS: A multicenter, international, randomized, controlled trial (RCT) was conducted. One hundred sixty-three patients, enrolled at 19 sites, were randomized 1: 1 to treatment with IPD or SDS and were followed for 24 mo. RESULTS: There was significant improvement in Zurich Claudication Questionnaire physical function, as mean percentage change from baseline, for both the IPD and the SDS groups at 12 mo (primary endpoint) and 24 mo (-32.3 +/- 32.1, -37.5 +/- 22.8; and -37.9 +/- 21.7%, -35.2 +/- 22.8, both P <.001). IPD treatment was not significantly noninferior (margin: 10%) to SDS treatment at 12mo (P=. 172) but was significantly noninferior at 24mo (P =.005). Symptom severity, patient satisfaction, visual analog scale leg pain, and SF-36 improved in both groups over time. IPD showed lower mean surgical time andmean blood loss (24 +/- 11 min and 6 +/- 11 mL) compared to SDS (70 +/- 39 min and 189 +/- 148 mL, both P <.001). Reoperations at index level occurred in 18.2% of the patients in the IPD group and in 9.3% in the SDS group. CONCLUSION: Confirming 3 recent RCTs, we could show that IPD as well as open decompression achieve similar results in relieving symptoms of NIC in highly selected patients. However, despite some advantages in secondary outcomes, a higher reoperation rate for IPD is confirmed.Medtronic Spinal and Biologic

Traumatic high-load injuries in the adolescent spine. Clinical, radiological and experimental studies

Background: Disc degeneration and other radiological abnormalities are highly frequent among young athletes in sports with great demands on the back. It has also been reported that athletes with these abnormalities have more back pain than other athletes and non-athletes. There is, however, incomplete knowledge regarding the effect of intensive physical loading on the spine, at what age various abnormalities occur and regarding the long-term effects on the morphological abnormalities and on the occurrence of back pain. Aims: It was hypothesised that high loads on the spines of athletes are correlated to an increased frequency of abnormalities and to back pain. The aim was to study the long-term outcome with regard to MRI-abnormalities and back pain. With the aid of an experimental porcine model, an aim was also to try to elucidate the mechanisms behind traumatic displacement of the ring apophysis, disc degeneration and endplate injuries found in adolescent athletes.Methods: Clinical studies: Twenty young elite divers were studied longitudinally (5 years) regarding MRI changes in the thoracolumbar spine and back pain symptoms. The frequency of MRI changes and back pain were also studied longitudinally (15 years) in 71 athletes (weight-lifters, wrestlers, orienteers, ice-hockey players) and 21 non-athletes. Back pain was assessed by questionnaires. Experimental studies: Normal discs and discs with experimentally-induced degeneration from young pigs were mechanically loaded in axial compression, flexion compression and extension compression to failure. The compression load and angle at failure were measured. The segments were then examined for injuries using X-ray, MRI and morphological and histological techniques. Additionally, a group of intervertebral discs with experimentally-induced degeneration were histologically examined regarding reactive and degenerative changes. Results and conclusions: Clinical studies: At the baseline assessment, MRI changes (primarily reduced disc signal) were found in 65% of the young elite divers and at 5 year follow-up deterioration had occurred in half the cases. New abnormalities in previously unaffected individuals occurred in only one case. Current or previous back pain was reported in 89%. Among the four groups of athletes, an even higher prevalence of MRI changes (91%) was found, while back pain was found in 78%. Disc degeneration was the most prevalent abnormality, and it progressed in a large proportion. Experimental studies: The spine in this porcine model was more susceptible to trauma in extension compression than in flexion compression Flexion compression and extension compression caused a fracture or separation of the endplate from the vertebral body in the growth zone in both normal and degenerated discs from young pigs. Axial compression of degenerated discs caused a fracture through the endplate and dorsal part of the vertebral body. In the histological study, the main finding was the demonstration of reactive repair processes that had replaced injured and degenerative structures with vascularised scar tissue. In conclusion, elite athletes run a high risk of developing disc degeneration and back pain. The growth zone and the endplate are the weakest parts in both normal and degenerated discs in growing porcine lumbar spines, when loaded in axial compression, flexion compression and extension compression. Neo-vascularisation of the central parts of the disc is likely to be of key importance in turning the degenerative features of the remaining tissue into reactive more normal structures

Evaluating a targeted person-centred pain management intervention programme in lumbar spine surgery - a controlled segment-specific before-and-after interventional design

Abstract Background Postoperative pain management in lumbar spine surgery care remains a challenge. The aim of this study was to evaluate the impact of a person-centred postoperative pain management intervention programme on lumbar spine surgery patients on postoperative pain, shared decision-making, and satisfaction with postoperative pain management. Methods The study was performed with a controlled before-and-after interventional design in an orthopaedic unit at a university hospital. Person-centred pain management for patients undergoing spine surgery was developed in co-creation by a multi-professional team and implemented throughout the care pathway. The usual care group (pre-intervention) served as a comparison to the intervention group. Pain intensity, shared decision-making in pain management, and patient satisfaction with results of pain management, served as patient-reported measures, collected using the International Pain Outcomes questionnaire and analysed using descriptive statistics. Results The intervention showed no benefit for patients’ pain and satisfaction, while shared decision-making in pain management was significant lower in the intervention group than in the conventional group. The per-protocol analysis showed no significant differences between groups. Conclusion The initial assumption of the study, that the implementation of a co-created structured person-centred care pathway would improve patient-reported outcomes, was not confirmed. The periodically low fidelity to the intervention due to organizational constraints (due to sub-optimal organizational conditions and managerial support) may have affected the results

Pathological Effects of Cortisol on Intervertebral Disc Cells and Mesenchymal Stem Cells from Lower Back Pain Patients

In western countries, lower back pain (LBP) is one of the most common disorders, experienced by more than 80% of the population. Chronic LBP due to disc degeneration has been linked to ongoing inflammatory processes in the disc and endplates. Pain effects the body in different ways, inducing a general stress response in which the body responds by releasing the stress hormone cortisol. Little is known about the impact of pain-induced stress on the progression of disc degeneration. Thus, the effects of cortisol on disc cells (DCs) and human mesenchymal stem cells (hMSCs) were explored in vitro with the objective of investigating the repercussions of cortisol on these cell types involved in de- and regenerative mechanisms of the disc. DC and hMSC pellet cultures were exposed to cortisol at two concentrations (150 and 300 ng/mL) for 28 days to simulate pain-induced stress. Cell viability, histological staining, and GAG DNA, along with apo-ptotic assays were conducted. Detection of OCT4, SOX9, IL-1R, and CXCR2 expressions was performed by immunohistochemistry. With cortisol treatment, restricted cell proliferation and less GAG production in both DCs and hMSCs were observed. Suppression of the differentiation and immunomodulatory efficacy of hMSCs was also detected. Moreover, elevated expressions of IL-1R and CXCR2 were detected in both cell types. To conclude, constant exposure to cortisol even at a physiological level enhanced pathological cellular processes in both DCs and hMSCs, which further jeopardized chondrogenesis. This suggests that cortisol resulting from pain-induced stress is a contributing component of intervertebral disc degeneration and may negatively affect regenerative attempts of the disc

The effect of repetitive flexion and extension fatigue loading on the young porcine lumbar spine, a feasibility study of MRI and histological analyses

Abstract Background The biomechanical mechanisms of failure of FSUs have been studied but the correlation of repetitive flexion and extension loadings to the initial phase of fatigue in young FSUs are still not known. The purpose of the study was to examine the fatigue results of low magnitude repetitive flexion and extension loading on porcine lumbar Functional Spinal Units (FSUs) with Magnetic Resonance Imaging (MRI) and histology. Methods Eight FSUs were subject to repetitive pivot flexion and eight to extension loading by a protocol of 20 000 cycles at 1 Hz with a load of 700 N. All loaded FSUs (N = 16) were examined with MRI and histology post loading. Three FSUs were examined with MRI as controls. Further three FSUs were non loaded histology controls. Results Fifteen (94%) of the loaded FSUs have decreased MRI signal in the growth zone of the superior vertebra and 12 (75%) in the inferior vertebrae. Fourteen (88%) FSUs have increased signal in the superior vertebral body. Fourteen (88%) FSUs have a reduced signal in all or any endplate. The histology morphometry displayed that the unstained parts of the epiphyseal growth zone were larger among the loaded FSUs (mean 29% vs 4%) and that the chondrocytes in the endplate and growth zones had abnormal structure and deformed extracellular matrix. Conclusion Repetitive loading of young porcine FSUs in both extension and flexion causes concurrent MRI and histological changes in the growth zones and endplates, which could be a first sign of fatigue and an explanation for the disc, apophyseal and growth zone injuries seen among adolescent athletes