A Systematic Review of Animal Studies and Human Clinical Trials. The Ritchie Centre, Monash Institute of Medical Research (MIMR- PHI), Monash University, Clayton Branch, P. O. Box 6. 17. 8, South Yarra, VIC 3. Australia. 2Departments of Surgery and The Ritchie Centre, Monash Institute of Medical Research (MIMR- PHI), Monash University, Clayton Branch, 2. Wright Street, Clayton, VIC 3. Australia. 3Proteobioactives Research Laboratories, P. O. Box 3. 5, Brookvale, NSW 2. Australia. 4Mesoblast Ltd, Melbourne, VIC 3. Australia. 5Department of Surgery, Monash University, Clayton, VIC 3. Australia. 6Department of Neurosurgery, Alfred Hospital, Level 5, The Alfred Centre, Commercial Road, Prahran, Melbourne, VIC 3. Australia. 7The Ritchie Centre, Monash Institute of Medical Research (MIMR- PHI), Monash University, Clayton Branch, 2. Diagnosis and Treatment of Low Back Pain: A Joint Clinical Practice Guideline from the American College of Physicians and the American Pain Society FREE. Home > American Journal of Roentgenology > Volume 188, Issue 3 > Sonography of the Neonatal Spine: Part 1, Normal Anatomy, Imaging Pitfalls, and Variations That May Simulate Disorders. During the 1990s and 2000s a large number of papers have been published on lumbar motor control training, led by researchers from the University of Queensland. Practitioners across the world now recognise that local (commonly. A lumbar puncture (LP), also known as a spinal tap, is a medical procedure in which a needle is inserted into the spinal canal, most commonly to collect cerebrospinal fluid (CSF) for diagnostic testing. The main reason for a. Cell-Based Therapies Used to Treat Lumbar Degenerative Disc Disease: A Systematic Review of Animal Studies and Human Clinical Trials. Objective To review the methods and complications of exposing the anterior aspects of the thoracic and lumbosacral spine. Data Sources PubMed (journals database of the National Library of Medicine), text books, the. Wright Street, Clayton, VIC 3. Australia. Copyright . This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Low back pain and degenerative disc disease are a significant cause of pain and disability worldwide. The mechanism of action of transplanted cells, as well as the limitations of published studies, will be discussed. Introduction. Low back pain is the leading cause of disability in the developed world and has an enormous social impact on patients and their families, as well as a devastating economic impact on healthcare budgets . The annual cost of back pain in the United States is estimated to be as high as $5. Studies have shown that 7. Severe disc degeneration is associated with a twofold increase in chronic low back pain . There are many potential pain generators in the lumbar spine in addition to the disc. Moreover, differentiating the ageing disc from the symptomatically degenerate disc remains a major challenge . Thin hyaline cartilage endplates attach the disc to the adjacent vertebral bodies and disc nutrition passes through these end plates to the predominantly avascular IVD . The IVD functions to facilitate movement and flexibility of the vertebral column, whilst also having the ability to recover from deformation following axial loading. The native cell population of the disc represents approximately 1% of the disc tissue but is pivotal in maintaining disc metabolism . Cells of the NP and inner AF demonstrate chondrocytic morphology whilst cells in the outer AF are more fibroblastic- like . An imbalance between extracellular matrix degradation and synthesis results in progressive collapse and mechanical failure of the disc. An overall decrease in resident disc cell number and function and cellular responses to nutritional deficiencies leads to alterations in both the cartilaginous and proteoglycan matrix components of the disc . The loss of the pivotal water binding proteoglycan component leads to dehydration of the NP, impacting the discs ability to adequately distribute and recover from mechanical loading. As degeneration progresses neovascularisation, with concurrent neoinnervation, can occur within the degenerative AF and extend to within the NP . Endplate changes occur with thinning, calcification, and alterations in vascularity, as nutritionally deprived discs attempt to increase their nutrient supply. This creates a hostile environment that is a major challenge to maintain cell viability of both native cells or cells that are implanted in regenerative therapies. For citation purposes: Johnson TG, Von SJ, Hope WW. Clinical anatomy of the abdominal wall: hernia surgery. OA Anatomy 2014 Jan 25;2(1):3. Why is MRI not used as the routine initial test for patients with LBP? Related questions concern which patients should get MRI without radiography and the importance of the spinal stenosis and disk protrusion identified on the. 90% of patients will have improvement of symptoms within 3 months with nonoperative care. Moreover, changes within the adjacent vertebral bodies and endplates occur, including sclerosis and subchondral bone microfracture . Initial treatments include conservative therapies such as analgesics, physical therapies, and psychological pain management strategies. When these nonoperative treatments fail, surgical interventions, such as lumbar fusion or total disc arthroplasty, are commonly performed. These treatments are often successful; however they do not address the underlying cause and, despite these interventions, some patients remain with chronic pain and disability. Substantial progress has occurred in the fields of regenerative medicine, tissue engineering, and stem cell therapies, with the aim of treating and reversing disc degeneration, as well as augmenting and enhancing current treatments. Clinical trials have commenced utilising cell- based biological therapies to treat many common diseases, including those affecting the musculoskeletal system and, in particular, degenerative discopathies. Culture expanded disc chondrocytes and mesenchymal stem cells, isolated from bone marrow or other sources, are the two cell types most commonly used by researchers to biologically repair the degenerate disc. Other types of stem or progenitor cells, used in either an autologous or allogeneic fashion, have also been investigated in studies. Several small clinical trials have recently been published with another larger randomised phase- 2 trial currently underway . Significant positive and negative findings of trials published to date will be highlighted, and the relative benefits and limitations of various cell types and treatment strategies will be discussed. Animal models of disc degeneration and the applicability of these models to the human condition will also be addressed. Knowledge of what has been achieved to date, as well as the limitations of these achievements, is important to guide future trials as this exciting field of regenerative medicine translates toward the clinic. Methods. We performed a literature search using the MEDLINE online electronic database between 1. Google Scholar, and the Cochrane Database. The following keywords were queried in combination with intervertebral disc: stem cell, mesenchymal stem cell, progenitor cell, nucleus pulposus cell, disc chondrocyte, disc regeneration, and tissue engineering. The search was limited to articles published in English. Studies utilising either stem cells, progenitor cells, or intervertebral disc chondrocytes to regenerate the intervertebral disc were included in the analysis. The indexes of suitable articles were reviewed for further relevant published studies. Publications comprised of in vitro work only were excluded. Studies were then grouped into one of the following four categories for analysis: (1) studies utilising chondrocyte transplantation, obtained from intervertebral disc tissue or other cartilage sources, (2) studies utilising stem and progenitor cell transplantation, including mesenchymal stem cells (MSCs) and other cell types obtained from noncartilaginous tissues, (3) studies comparing chondrocyte and stem cell transplantation, and (4) human clinical trials utilising any form of cell- based therapy to repair degenerative discs, including chondrocytes and stem cell therapies. The flow diagram for our search is outlined in Figure 1. Figure 1: Flow diagram demonstrating the systematic analysis process. Studies Utilising Intervertebral Disc or Chondrocyte (or Chondrocyte- Like) Cell Transplantation. There were 1. 4 studies identified assessing the ability of disc derived and nondisc derived chondrocytes to regenerate IVDs, as shown in Table 1. Table 1: Studies assessing the ability of disc derived and non- disc derived chondrocytes to regenerate lumbar intervertebral discs. Animal Models Utilised. It should be noted that the amount of nuclear material removed in the nucleotomy procedure differed between studies and is listed in Table 1. Cell Types Utilised. NP cells into target discs. The remaining studies utilised AF cells, NP tissue, or whole disc. Allogeneic administration was performed in 1. NP cells were injected into the rabbit disc . Outcomes. In 1. 2/1. T2 signal on MRI. Gruber et al. No other cell related morbidity or negative outcomes were reported in any other study utilising chondrocyte transplantation. Studies Utilising Stem Cell and Progenitor Cell Transplantation. There were 2. 5 studies assessing the ability of different types of stem cells or progenitor cells to regenerate the IVD identified, as shown in Table 2. Table 2: Studies assessing the ability of different types of stem cells or progenitor cells to regenerate lumbar intervertebral discs. Animal Models Utilised. The remaining 2. 2/2. Cell Type Utilised. Bone marrow derived MSCs were the most commonly used stem cell treatment, used in 2. MSCs, 7/2. 5 used allogeneic administration, and 4/2. MSC xeno- transplantation to treat degenerate animal discs. MSCs, either autologous or xenogeneic human MSCs, whilst other cell types investigated included human embryonic stem cells (ESCs), autologous synovial derived MSCs, human olfactory neurosphere derived stem cells, and allogeneic mesenchymal precursor cells (MPCs). Puramatrix, or PFG- TGF- beta. Outcomes. The outcomes of these studies are summarized in Table 2. MRI T2 signal, following cell administration. GAG or collagen II content or measuring expression of genes known to be important for matrix restoration, such as Col. Sox- 9. 1. 2/2. 5 studies assessed the viability of cells following transplantation with varying survival times reported, ranging from 1. Several other studies, however, reported leakage or nonviability of cells following injection. Studies Comparing MSC and Chondrocyte Transplantation. Three studies directly compared the ability of MSCs and chondrocytes to regenerate IVDs . When used alone, however, both the MSCs and NPCs were equally ineffective in repairing the damaged rat disc. Table 3: Studies comparing the efficacy of MSCs and chondrocytes to regenerate lumbar intervertebral discs. These allogeneic MSCs were found not to be viable at 3 months and there was no evidence of proteoglycan production in their model. Clinical Trials Utilising Cell Based Disc Therapies. Four published clinical studies utilising cell- based therapies to treat human lumbar disc degeneration were identified . Three of these studies reported favourable results. The Euro. DISC study, by Meisel and colleagues .
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