Interaction of Human Mesenchymal Stem Cells With Disc Cells

Visage, Catherine Le; Kim, Seok Woo; Tateno, Kei; Sieber, Ann N.; Kostuik, John P.; Leong, Kam W.

doi:10.1097/01.brs.0000231442.05245.87

Cited by 87 publications

(65 citation statements)

References 12 publications

(10 reference statements)

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“…Furthermore, MSCs stimulate tissue-associated stem cells to differentiate to target tissues . Le Visage et al (2006) found that proteoglycan synthesis increased when MSCs were co-cultured with annulus fibrosus cells, and Sakai et al (2006) reported increased proteoglycan and extracellular annulus fibrosus matrix synthesis, and the restoration of water disc height after transplanting MSCs into IVDs in an rabbit model, which was similar to that found by Sakai et al (2006).…”

Section: Discussionsupporting

confidence: 69%

“…However, these approaches cannot be viewed as fundamental treatments for IVD degeneration because they do not address its cause. Recently, the molecular biological characteristics of IVD degeneration were identified, and treatment strategies are being sought that regenerate IVDs by restoring extracellular matrix or cellular components in animal models (Crevensten et al 2004;Le Visage et al 2006;Sakai et al 2006Sakai et al , 2005Sakai et al , 2003.…”

Section: Introductionmentioning

confidence: 99%

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Human mesenchymal stem cells implantation into the degenerated coccygeal disc of the rat

et al. 2009

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In this study, the authors explored the effect of human mesenchymal stem cell (MSC) implantation on the restoration of degenerative intervertebral discs (IVDs) in the rat. A unique rat coccygeal model was used to investigate the effects of transplanting human MSCs and to examine MSC survival in degenerative discs. MSC implantations into rat coccygeal IVDs were performed at 2 weeks postinjury. Radiologic and histologic evaluations were performed at 2, 4, 6, and 8 weeks post-injury. MSCinjected segments (TS) retained disc height and signal intensity, but injured non-injected segment (IS) progressively lost disc height. Pathological results revealed that the TS group showed relative restoration of the inner annulus structure; however, the IS group showed destruction of the inner annulus structure. Immunohistochemical staining using Anti-Human Nucleic Antibody (#MAB1281 Chemicon) revealed positive staining in the TS group at 2 weeks posttransplantation (4 weeks post-injury). This study shows that human MSCs survive for 2 weeks after transplantation into the IVDs of rats, and that MSCs increased the heights and signal intensities of intervertebral disc.

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Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Human mesenchymal stem cells implantation into the degenerated coccygeal disc of the rat

et al. 2009

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“…At this early stage, matrix loss is still limited or partial and there is no need to replace the bulk matrix. As a result, minimally invasive treatments such as injecting growth factors to stimulate the NP cells to synthesize proteoglycans [74] or injecting cells able to synthesize appropriate ECM such as bone marrow mesenchymal stem cells [48,67,108] are the most commonly proposed. Nevertheless, one important inadequacy of this approach is that the high disc pressure and the aqueous nature of the cell suspension usually result in depletion of the local availability of cells [5,53].…”

Section: Scaffolding In Intervertebral Disc Tissue Engineeringmentioning

confidence: 99%

Scaffolding in tissue engineering: general approaches and tissue-specific considerations

2008

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Scaffolds represent important components for tissue engineering. However, researchers often encounter an enormous variety of choices when selecting scaffolds for tissue engineering. This paper aims to review the functions of scaffolds and the major scaffolding approaches as important guidelines for selecting scaffolds and discuss the tissue-specific considerations for scaffolding, using intervertebral disc as an example.

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“…6,7,35 Recent attempts to supplement the disk's regenerative capabilities and prevent tissue degradation have already shown promising results using both cell-based and gene therapeutic approaches. [54][55][56] Furthermore, an elegant therapy approach that would directly address and neutralize the apoptosis-inducing ligand TRAIL might help to at least delay progression of disk degeneration. A comparable approach that involves FasL function perturbing antibodies has already shown promising results in the regeneration and functional recovery after spinal cord injury in an animal model.…”

Section: Discussionmentioning

confidence: 99%

Expression of TRAIL and the death receptors DR4 and DR5 correlates with progression of degeneration in human intervertebral disks

et al. 2009

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Intervertebral disks degenerate far earlier than other musculoskeletal tissues and apoptosis has been suggested to have a vital function in promoting the degeneration process that is strongly associated with back pain. However, the molecular mediators of apoptosis in the intervertebral disk are poorly understood. Fas/FasL, TRAIL/DR4, TRAIL/DR5 and TNF-a/TNFR1 are ligand/receptor pairs of the tumor necrosis factor/nerve growth factor family, which are able to induce apoptosis by trimerization of the receptor by its corresponding ligand. We investigated which of these molecules are expressed in intervertebral disks and whether their expression correlates to disk degeneration. Intervertebral disks from 28 donors (age 12-70 years) suffering from scoliosis, vertebrae fracture or disk degeneration were scored histologically for degeneration and analyzed for gene expression of FasL/Fas, TRAIL/DR4, TNF-a/TNFR1 and caspase 8. Protein expression of FasL and TRAIL was assessed by immunohistology and apoptotic cell death was quantified by poly(ADP-ribose) polymerase (PARP) p85 staining. Isolated disk cells were analyzed by flow cytometry for Fas, FasL, TRAIL, DR4 and DR5 expression. Gene expression of TRAIL (P ¼ 0.002) and caspase 8 (P ¼ 0.027) significantly correlated with degeneration. TRAIL expression further correlated with cellularity (P ¼ 0.04), muccoid matrix changes (P ¼ 0.009) and tears and cleft formation (P ¼ 0.019). FasL and TRAIL expression was confirmed by immunohistology and PARP cleavage was significantly associated with degeneration (P ¼ 0.027). Flow cytometry on isolated disk cells revealed correlations between DR4 and degeneration (P ¼ 0.014), DR4/DR5 double-positive cells and degeneration (P ¼ 0.019), as well as DR5 and changes in tissue granularity (P ¼ 0.03). This is the first study that shows that intervertebral disk cells express TRAIL, DR4 and DR5, which correlate to the degenerative state of the disk. Therefore, disk cells inherit the molecular machinery to induce and undergo cellular apoptosis, and the frequency of cytokine expression suggests that the TRAIL/DR4/DR5 axis is an important molecular mediator of apoptosis induction in disk tissue. Modern Pathology (2009) 22, 895-905; doi:10.1038/modpathol.2009 published online 20 March 2009 Keywords: apoptosis; TRAIL; DR4; DR5; intervertebral disk; degeneration Low back pain is a leading cause of morbidity. It is estimated that about 70% of the population will experience low back pain during their lives. 1 In recent years, intervertebral disk disorders and agerelated degeneration have been significant contributors to low back pain and spine-related disability.The intervertebral disk is the largest avascular organ in the body, populated by highly differentiated cells within an extensive extracellular matrix. The nucleus pulposus is highly hydrated and proteoglycan rich encapsulated by the dense collagenous fibrous tissue of the annulus fibrosus and by the cartilaginous endplates.There is great interest in understanding the complex pathogenesis of in...

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Interaction of Human Mesenchymal Stem Cells With Disc Cells

Abstract: Addition of MSCs to AF cells resulted in an up-regulation of the proteoglycans synthesis. This study provides the rationale for further investigation of the potential of MSC therapy in treating intervertebral disc degeneration.

Cited by 87 publications

References 12 publications

Human mesenchymal stem cells implantation into the degenerated coccygeal disc of the rat

Human mesenchymal stem cells implantation into the degenerated coccygeal disc of the rat

Scaffolding in tissue engineering: general approaches and tissue-specific considerations

Expression of TRAIL and the death receptors DR4 and DR5 correlates with progression of degeneration in human intervertebral disks

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